Module 1.

Introduction, History and Medical Aspects of HIV


COURSE DESCRIPTION
This training module has been developed for vocational rehabilitation counselors to provide current information on HIV disease and the clinical manifestations and functional limitations of HIV/AIDS disability. The participant will learn about HIV infection and the immune system; progression of HIV disease; clinical manifestations, opportunistic infections, and malignancies associated with HIV infection; common symptoms of HIV related illnesses; and treatment issues.

GOALS
The participant will view HIV disease as a long-term, chronic disability when planning and delivering rehabilitation services to HIV infected consumers.

OBJECTIVES
Upon completion of this training module, the participant will be able to:
1. Understand the history of HIV and the scope of the epidemic
2. Describe the relationship between the immune system and HIV infection.
3. Discuss the progression of HIV disease along the continuum of disability.
4. List symptoms associated with HIV disease/AIDS that a client may experience and several of the diseases/conditions/factors that may cause them
5. Describe and discuss the functional limitations associated with HIV/AIDS associated diseases/conditions/factors/treatments causing disability
6. Use the reference materials provided

MATERIALS NEEDED
35mm projector
Paper for the class activity
Easel Paper and pens/blackboard for recording points from class discussion

MATERIALS INCLUDED
Module
Class activity/Progressive Vignettes
Reference Material including:
Reference A. Scope And Impact Of HIV Disease
Reference B. CDC First 500,000 Cases
Reference C. History Of HIV Disease
Reference D. Clinical Manifestations
Reference E. Drug Side Effects
Reference F. Clinical Manifestations By Organ System
Reference G. Monitoring The HIV-Infected Individual
Reference H. Glossary
Reference I. HIV Transmission and Risk Reduction


INTRODUCTION, SCOPE OF HIV DISEASE/AIDS

You are all experienced rehabilitation counselors. We are here to focus attention on HIV disease and AIDS, guide you through the reference materials you've been given and, hopefully, supplement your expertise. This will also be an opportunity for you to share your knowledge and experience with your colleagues. Each office probably operates differently and this is an opportunity to share your different approaches.

HIV disease/AIDS is long term, chronic, often disabling, at least somewhat manageable disease. AIDS is the advanced, often fatal form of HIV disease.

World Statistics
AIDS has been reported in over 150 countries
Estimates are that 22 million people have been infected with HIV
Expectations are that 35- 40 million will be infected by the year 2000
By the year 2000 it is expected that 10,000,000 children will be orphaned because of HIV disease

Figure 1.1 Death Rates in U.S.
In the United States AIDS is the leading cause of death in all Americans ages 25-44


AIDS affects every aspect of American life from individuals, families, cities, states, the federal government, schools, businesses, the judicial system, and religious institutions. Issues surrounding HIV disease deal with three factors with which we do not deal well:
death and dying
sexuality
diversity.

UNITED STATES STATISTICS as of 6-30-96
AIDS: 548,102
Deaths: 343,000
Figure 1.2 U.S. Statistics of HIV


California Statistics as of 3-97
AIDS: 99,908
Deaths: 64,137

Your Area Statistics (e.g. San Francisco)
In San Francisco, as of 3-97 there had been 24,053 cases reported, with 16,718 deaths. These figures represent more deaths from AIDS in San Francisco than in all the U.S. wars to date.

HIV Disease is a disease of reproductive aged individuals. It affects those who provide for the young and aged. It is a disease of those who normally are working. This has great implications for Vocational Rehabilitation counselors.

HIV disease disproportionately and severely affects people of color and the economically disadvantaged People of color represent approximately 20 percent of the U.S. population and 50 percent of the AIDS cases


Figure 1.3 Ethnic Distribution

See Reference A: Scope and Impact of HIV Disease


HISTORY OF HIV DISEASE
In the spring of 1981 the United States Public Health Service Centers for Disease Control (CDC) began receiving reports of cases of Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma (KS) in previously healthy young gay males in Los Angeles, New York and San Francisco. While the fungus Pneumocystis Carinii is widespread in the lungs of U.S residents, it does not usually cause pneumonia. PCP is usually found only in people whose immune systems are not functioning properly, such as those who lack immune response because of genetic diseases and those who are receiving cancer chemotherapy or immunosuppressive therapy for organ transplants. Kaposi's sarcoma (KS) is usually seen in older men of Mediterranean heritage, and in whom this cancer of the walls of blood vessels is not a fatal disease. It soon became apparent that these young men were also unable to mount an immune response against other viral, bacterial and parasitic infections, the opportunistic infections (OIs), and a large percentage of them were dying. In December 1981, reports in the New England Journal of Medicine demonstrated that the original individuals reported to the CDC had decreased counts of specialized white blood cells, the T lymphocytes. The initial belief was that the immune system dysfunction that permitted the development of these opportunistic infections (OIs) was somehow related to the gay lifestyle. Use of inhalant drugs, treatment for a number of sexually transmitted diseases, multiple sexual partners, and antigen overload from sperm introduced into the rectum in anal sex, were part of the history of many of the patients being seen with this new phenomenon. All of these had been shown to be immunosuppressive. This is why the term Gay Related Immune Deficiency (GRID) was the name first applied.

Soon others beside gay men were seen with the syndrome: recipients of blood and blood products (such hemophiliacs, sexual partners of those affected, and children born of affected mothers.

While in 1981 in the U.S. illness was initially seen in young gay men, the demographics continue to change and now we are seeing more women and adolescents being diagnosed with AIDS.

See Reference B: CDC-The First 500,000 Cases of AIDS

The disease was named Acquired Immune deficiency syndrome (AIDS).
A.I.D.S.= Acquired Immune Deficiency Syndrome
Acquired: Contracted , not inherited
Immune: Involving the body's system for fighting Disease
Deficiency: The immune system is not functioning properly making the body vulnerable to certain life-threatening illnesses to which it would not ordinarily be susceptible
Syndrome: A group of symptoms or conditions


HUMAN IMMUNODEFICIENCY VIRUS (HIV)
By 1984 the organism believed to be responsible for AIDS, Human Immunodeficiency Virus (HIV) was identified. The protein parts of HIV can be recognized by the immune system and within 2 weeks to six months after infection the body produces antibodies against those antigens. This is the basis for the "AIDS antibody test".
Figure 1.4 HIV Virus


HIV Structure
HIV has as its genetic core RNA with two associated molecules of an enzyme called reverse transcriptase (RT), and two other enzymes integrase and protease. (Enzymes are catalysts, that is, they initiate or speed up chemical reactions. In this case, RT causes the reverse transcription of DNA from RNA.) The retroviruses are named for the fact they have an RNA genome that is "reverse transcribed" into DNA by reverse transcriptase. [Most viruses have a DNA genome, which is transcribed into RNA and messenger RNA (mRNA).] Surrounding the RNA and enzymes are two layers of protein forming a conical protein core or nucleocapsid . The proteins composing the core are p17(18) and p24. Outside the core is an envelope the virus acquires from the infected host cell by a process called budding. The host-cell membrane is modified by the insertion of two viral glycoproteins (combinations of sugar and proteins) gp120 and gp41. Both gp120 and gp41 have important roles in the binding of HIV to cells in the infection process.

This is a virus which becomes a permanent part of the cells and tissues it infects disrupting their function, causing cancer or destroying them. It uses several cells of the immune system to reproduce itself, and is vulnerable to attack at may stages of its "life cycle."

HIV "Lifecycle" And Points Of Potential Interference
Figure 1.5 HIV Lifecycle


HIV is particularly susceptible to inhibitors of the three viral enzymes needed for the virus to infect a cell or for viral replication. Inhibitors of reverse transcriptase and protease have been shown to be effective. It is hoped that an effective integrase inhibitor will be available soon.

HIV Transmission
HIV and HIV infected cells have been shown to be transmitted from one person to another by:
a. Blood and blood products
b. Semen
c. Vaginal fluids
d. Breast milk

Transmission can take place:
a. across mucous membrane (sexual intercourse; blood splashing in eyes, etc.)
b. through broken skin (cuts, rashes etc.)
c. by injection (sharing of injecting drug paraphernalia; needle stick injuries etc.)
d. perinatally during pregnancy or childbirth
e. via breast feeding


Figure 1.6 HIV Transmission methods



The Effects Of HIV Infection
Currently, HIV disease is considered one in which a cure may or may not be possible but in which early intervention is likely to improve survival. HIV disease is now viewed as a long-term chronic disability that requires health care planning and management, as well as rehabilitation counseling along a chronic disease continuum. The goal of this section is to supply information Vocational rehabilitation (VR) counselors need to provide competent service to individuals infected with HIV.


HIV infection affects the human body in a number of ways.
1. Direct effect of HIV on body cells or tissue: Nervous system cells, Cells of the digestive tract, Cells which line the body organs, Cervical cells, Epididymis, Fibroblast and osteogenic cells, Placenta, Adrenal gland cells, Lung alveolar cells, Lung macrophages
2. Indirect disruption of tissue function by immune system components, e.g. Tumor Necrosis Factor (TNF) from activated immune system cells may cause wasting syndrome
3. Disruption of immune function which results in the development of opportunistic infections (OIs) and cancers
4. Negative effects of drugs or other methods used to combat infection, OIs or cancers
5. Psychological reactions

There may be an overlap of effects in a particular organ or organ system. For example, the nervous system may be affected in all 5 ways. The brain may be affected directly by HIV on nervous system cells; indirectly by infected cells or immune system cells producing substances which affect surrounding brain and nervous system tissue; by OIs and cancers that affect the brain; by negative effects of drug treatments or drug use on the brain; and by the psychological reactions connected with having a chronic, disabling disease that may result in the person's death.

HIV infects many cells and tissues in the body including major organs including the heart, the lungs, kidneys, the retina of the eye, cells which line the body organs, the cervix, the epididymis, sperm, the endocrine system, the nervous system, the digestive tract, and the placenta. It is particularly damaging to the immune system.

OVERVIEW OF THE IMMUNE SYSTEM AND HIV DISEASE
The immune system is a complex network of specialized cells and organs that defends the body against "foreign" invaders. When functioning properly, it combats infections by pathogens such as bacteria, viruses, fungi, and protozoa, as well as destroying body cells that have been altered, such as cancer cells or virus infected cells. When the immune system is disrupted, a number of conditions may manifest themselves, including autoimmune responses, cancers, and infections that would normally be contained (opportunistic infections-"OIs") by an intact immune system.
The immune system recognizes and responds to molecules (antigens) that are foreign or non-self (altered cells). When Human Immunodeficiency Virus (HIV) enters the body, the immune system responds to a number of antigens specific to HIV. White blood cells, the lymphocytes and phagocytes, which are produced in the bone marrow, carry out important aspects of the immune system's activities. The phagocytic cells, such as macrophages and dendritic cells ingest, process, and destroy foreign organisms. They interact with, and activate the orchestrator of the immune response the T-helper (TH) lymphocyte. The activated TH cell, in turn, activates ("helps") two major classes of lymphocytes, the B lymphocytes and the T-cytotoxic lymphocytes, to fight disease. One specialized type of TH cell destroys cells that are infected by organisms that live inside of cells (intracellular parasites), many of which cause the opportunistic infections seen in HIV disease.

When activated by the TH cells, the B cells produce specific antibodies which bind to and destroy specific foreign antigens.

When activated by the TH cells, T-cytotoxic cells contribute to the immune defenses by recognizing and destroying altered self cells, such as cancer cells and virus infected cells.

Therefore, the two types of T-lymphocytes function somewhat differently. They are also characterized by different marker molecules on their surface membranes.

The T-cytotoxic cells display the CD8 molecule; the TH-lymphocytes display the CD4 molecule. (Other cells in the body also display the CD4 molecule in lower numbers).

Figure 1.7 Immune System Overview


HIV has an affinity for cells that express the CD4 molecule. After binding to CD4 and infecting the cell, HIV subverts the normal functioning of the cell in order to reproduce itself. The combination of actions by HIV and components of a chronically activated immune system, results in the progressive loss of TH cells and significant disruption of the immune response. The immune system becomes unable to respond effectively not only to HIV (resulting in an increase in the viral load in the blood), but to other organisms normally destroyed by TH and TC cells as well. HIV may also infect other tissue and organs interfering with their functioning. Continuous, chronic activation of the immune system results in the production of components that may also cause disruption of body functions.

Typical Pattern of HIV Disease/Stages of HIV Disease
Not everyone who is infected with HIV will show disease progression to an AIDS diagnosis. Estimates are that somewhere between 3% and 15% of those infected with HIV will not. Many persons, however, will manifest disease states.
The spectrum of disorders associated with HIV Disease can be viewed on a continuum beginning with an acute infection shortly after HIV enters the body. Typically, after the acute phase, HIV Disease is characterized by a long period in which the immune system combats HIV effectively. This is followed by some clinical manifestations of disease which may be problematic but are not life threatening. This stage is typically followed by a severe decline in TH cells, an increase in viral replication resulting in an increase in viral load in the blood, and the appearance of opportunistic infections and cancers. Thus, there is progression through acute, early, middle, advanced and late stage disease. The term AIDS (advanced and late stage disease) is a definition, established by the CDC. It is based on the CD4 count or percentage of total lymphocytes; or the presence, location and/or severity of specific conditions, opportunistic infections, or cancers.

Figure 1.8 Typical Path of HIV

Adapted from Sande MA, Volberding PA: The Medical Management of AIDS, 5th Ed., WB Saunders Co., 1997. (Figs. 3-1, 4-6)

NOTE: A Normal CD4 count is 800-1200
Acute infection: a drop in CD4 count occurs initially, then rises to normal limits
Early stage of HIV disease-CD4 count >500
Middle stage 200-499
Advanced stage <200
Late stage <50

Acute Infection
One to 12 weeks after infection with HIV, a mononucleosis or Flu type syndrome may occur which lasts for three to 49 days. Symptoms may include fever, fatigue, vomiting, sweating, sore throat, lymphadenopathy, diarrhea, encephalopathy, peripheral neuropathy. occasionally pneumonia of undetermined origin, and a red, blotchy rash on the trunk. Deaths have occurred in the acute stage. However, the initial infection may be very mild. The initial infection usually results in antibody formation between two and 24 weeks (six months) after the acute illness, and the person becomes antibody positive. Those who are antibody-positive are considered infectious. This period is associated with high levels of virus in the blood and a severe, temporary, drop in CD4 count.

Early Stage Disease; (Asymptomatic Infection) CD4 count >500
(defined as the absence of signs or symptoms of HIV infection.) This is the clinically latent phase of the disease where few, or no clinical manifestations of HIV disease are seen. This typically lasts for years. The person living with HIV infection generally looks and feels well. However, typically, during this period, up to two billion new CD4 TH cells and ten billion new viral particles are being produced and destroyed daily as the immune system responds to HIV infection.

Early to Middle Stage disease CD4 count 200-499
The immune system gradually succumbs to the virus resulting in an increase in viral replication and increase in clinical manifestations including swollen glands (Persistent generalized lymphadenopathy or PGL), fever, night sweats, weight loss, diarrhea, oral lesions, and skin disorders.

Persistent Generalized Lymphadenopathy (PGL). This involves lymph node enlargement of 1 cm or greater at two or more extra inguinal sites persisting for more than three months in the absence of a concurrent illness or condition other than HIV infection to explain the findings). While PGL is not indicative of progression to AIDS, HIV can destroy the integrity of the lymph node. PGL may decrease prior to an AIDS diagnosis, which may be indicative of immune system failure. In AIDS the lymph nodes regress and may be difficult to detect clinically. On autopsy they have atrophied.

Advanced Stage Disease (AIDS) CD4 count <200
In typical HIV Disease, eventually the presence of AIDS defining illnesses is seen. The rate of progression to AIDS after initial infection appears to vary and may change with time. Overall, AIDS is unusual within the first several years after seroconversion. The average interval from seroconversion to AIDS appears to be 8-12 years.

Late Stage Disease (AIDS) CD4 count<50
Serious opportunistic infections and cancers are seen in this stage. A CD4 count under 50 is predictive of death within one year, median survival time is 9 months. However, many people have lived for years in this stage.

Non-progressors Vs Long term survivors
A non-progressor is a person in whom HIV disease does not progress or progresses slowly (slow progressor)
A long term survivor is a person who survives longer than average after an AIDS diagnosis

Disease progression
Death can occur during acute infection
Progression to AIDS can be as short as 2-4 months (rapid progressor)
Some people have remained healthy for over 18 years.


MANIFESTATIONS OF HIV DISEASE
Opportunistic infections (OIs) or Secondary Infectious Diseases or Cancers Associated with HIV Disease

To understand the clinical aspects of the development of opportunistic infections (OIs) associated with AIDS, the reader must be aware of some generalizations that can be made about their presence in an HIV-infected client. OIs are caused by a diverse spectrum of pathogens, many of which rarely cause disease in individuals with an intact immune system.

Infectious diseases have caused approximately 90% of "AIDS" deaths.
• Many of the organisms causing the OIs are found in the general population and are kept under control by an intact immune system.
• Some of these clearly constitute an AIDS diagnosis.
• In some cases, as in candidiasis, the place found or the degree of infection determines whether the disease qualifies as an AIDS diagnosis
• Some OIs are predicative of progression to AIDS, while others may be present but are not predictive.
• The diseases seen depend upon where they appear endemically (geographical location)
• HIV disease can result in activation of prior infections such as TB, Syphilis, and varicella (shingles)
• Most of the OIs are not contagious from one person to another. They tend to be organisms that are present, often found in other species (cat, rodents, and birds) but generally do not cause disease in humans unless the immune system is disrupted. Two exceptions to this are TB and syphilis.
• TB is spread by droplet infection via coughing. People have become infected with the TB bacillus merely by sitting in the same office with someone with active pulmonary tuberculosis. In clinical settings where people are coughing, professional staff are advised to wear masks. Counselors need to address the issue with clients who are coughing. The cause of the cough needs to be determined and appropriate precautions taken.

Categories of Opportunistic Infections (OIs) Associated with HIV Disease
1. Protozoal Infections. Protozoa are the simplest, often one-celled, animals
2. Viral Infections. Virus = simple, minute parasitic organism that cannot reproduce outside of a living cell. They can only be seen with an electron microscope. These may also act directly to lower the immune response.
3. Fungal Infections Fungus = a plant-like organism
4. Bacterial Infections (commonly found in HIV-infected children) Bacteria = microorganisms of three forms: spherical or ovoid; rod shaped; spiral.
5. Mycobacteria = rod shaped, gram positive acid-fast bacteria
6. Cancers that may be caused by an infectious organism.

Table 1.1 Cancers and Causative Agents
CANCER CAUSATIVE AGENT
Kaposi's Sarcoma HHV-8
Lymphoma EBV
Cervical cancer HIV + HPV
Anal cancer HIV + HPV

Figure 1.9 Direct Effects of the Virus


Symptoms therefore may include:
Fatigue Fever
Coughing Diarrhea
Vision impairment Hearing impairment
Neurological involvement Loss of weight

Neurologic disease is seen. (A prime example of the complexity of HIV disease.)(AIDS Health Project)

Defined as one or more of the following:
1. dementia (insanity)
2. myelopathy (muscle weakness)
3. peripheral neuropathy (problems with the peripheral nerves--hands feet etc.)
4. and the absence of conditions other than HIV infection to explain the findings.

HIV associated dementia is a neurobehavioral deficit that is a common neurological complication of late-stage disease. The tissue changes in affected individuals appears to involve the white matter in the brain, the spinal cord, and subcortical gray matter with significant damage to neurons.

Wasting Syndrome or Slims disease. This is like the cachexia or wasting seen in cancer. It is most likely a result of chronic activation of the immune system.

See Reference D: Clinical Manifestations

CURRENT DIAGNOSTIC CRITERIA FOR AIDS
(ADVANCED OR LATE STAGE HIV DISEASE)
The following is based on MMWR.1993. Vol. 41/RR-17.

The criteria for an AIDS diagnosis include three clinical categories of HIV infection which are hierarchical (classification/diagnosis based on highest lettered category)
The severity or location of disease may determine whether or not it constitutes an AIDS diagnosis.
The CD4 count or percentage of total lymphocytes and Clinical categories are both used in the determination of an AIDS diagnosis

Table 1.2 1993 Revised Classification System for HIV Infection ;and Expanded AIDS Surveillance Case Definition for Adolescents and Adults*
Clinical Categories

CD4 T-cell
categories (A)
Acute (primary) HIV infection, Asymptomatic, or PGL** (B)
Symptomatic, not (A) or (C) conditions*** (C)
AIDS-indicator
conditions
(1) > 500/ml A1 B1 C1
(2) > 200-499/ml A2 B2 C2
(3) < 200 ml
AIDS indicator
T-cell count
A3
B3
C3
* AIDS indicator conditions (Category C) as well as those with CD4 T-lymphocyte counts <200/ml (Categories A3 or B3 will be reported as AIDS cases in the United States and Territories, effective January 1, 1993
** PGL- Persistent generalized lymphadenopathy. Clinical Category A includes acute (primary) HIV infection
The bold, underlined cells illustrate the expanded AIDS surveillance case definition.

Category (A) includes one or more of the following conditions in an individual 13 years of age or older. Category B and C conditions must not have occurred.

Not AIDS diagnosis unless CD4 count under 200 or 14%. of total lymphocytes

Examples of Category A conditions:
Acute infection
Asymptomatic infection
Persistent generalized Lymphadenopathy.

Category (B) includes symptomatic conditions, in an HIV-infected individual 13 years of age or older, that are not included in clinical category C. They must meet one of the following criteria:
1. They must be attributed to HIV infection or are indicative of a defect in cell mediated immunity; or
2. the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection.

Not an AIDS diagnosis unless CD4 count under 200 or 14% of total lymphocytes

Examples of Category (B) conditions (these have been referred to as AIDS Related Conditions or ARC)
Bacillary angiomatosis
Candidiasis, oropharyngeal (thrush) (not in esophagus, bronchi, trachea or lungs)
Candidiasis, vulvovaginal; persistent, frequent or poorly responsive to therapy
Cervical dysplasia (moderate or severe)
Cervical cancer in-situ (localized)
Constitutional symptoms, such as fever (38.5 C) or diarrhea lasting more than one month
Oral Hairy leukoplakia
Herpes Zoster (shingles), involving at least two distinct episodes or more than one dermatome
Idiopathic thrombocytopenic purpura
Listeriosis
Pelvic inflammatory Disease, particularly if complicated by tubo-ovarian abscesses
Peripheral neuropathy (disease of the peripheral nerves)

Category (C) includes the clinical conditions listed in the AIDS surveillance case definition. An AIDS diagnosis regardless of CD4 count in an HIV positive individual.

Examples of Category (C) conditions:
Candidiasis of bronchi, trachea or lungs
Candidiasis of esophagus
Invasive cervical cancer
Coccidiomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal of more than one month's duration
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV-related ( Cerebral atrophy) (AIDS Dementia Complex) Clinical findings of disabling cognitive or motor dysfunction interfering with occupation or daily living, progressing over weeks to months, in the absence of a concurrent illness that could explain the findings
Herpes Simplex: chronic ulcer(s) of more than one month's duration; or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isoporiasis, chronic intestinal of more than one month's duration
Kaposi's sarcoma
Lymphoma, Burkitt's (or equivalent term); Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of the brain
Mycobacterium avium complex or M. Kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis , any site (pulmonary or extrapulmonary)
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Pneumonia, recurrent
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of the brain
Wasting syndrome due to HIV (profound involuntary weight loss of more than 10% of baseline body weight plus either chronic diarrhea (at least 2 loose stools per day for 30 days or longer. Or chronic weakness and documented fever for 30 days or longer, intermittent or constant, in the absence of a concurrent illness or condition other than HIV infection that could explain the findings (e.g. cancer, tuberculosis, cryptosporodiosis, or other specific enteritis).

AIDS diagnosis based on percentage of CD4 lymphocytes of total lymphocytes. Equivalencies for absolute numbers of CD4+ T-lymphocytes and CD4 percentages*

Table 1.3 AIDS diagnosis based on percentage of CD4 ;
CD4+ T-cell Category CD4+ T-cells/ml CD4+ percentage (%)
(1) >500 >29
(2) 200-499 14-28
(3) <200 <14
*The percentage of lymphocytes that are CD4+ T-cells

Clinical appearance of diseases related to CD4 count
Generally speaking, OIs are matched with the CD4 count. Below are the CD4 counts at which the following OIs and HIV-related conditions usually make their clinical appearances:
Table 1.4 Clinical appearance of diseases
> 500 cells/mm3 Tuberculosis reactivation
Cervical Cancer
Bacterial infections
250-500 cells/mm3 Kaposi's sarcoma
200-250 cells/mm3 Pneumocystis carinii pneumonia (PCP)
150-200 cells/mm3 KS
Lymphoma
Cryptosporidiosis
75-125cells/mm3 Toxoplasmosis PCP
MAC Herpes Simplex Virus
Cryptococcosis Esophogeal candidiasis
Under 50 CMV Retinitis
MAC
Dissemination of strongyloides stercoralia (round worm)
MONITORING THE HIV-INFECTED INDIVIDUAL
The two most important indicators of HIV progression, currently, are the CD4 count and the viral load. Increased viral load and decreased CD4 count are indicative of disease progression.

The clinical manifestations predictive of progression to AIDS are:
Oral disease
Thrush
Hairy leukoplakia
Decreased skin test response (anergy)
A severe acute stage
Repeat acute stage two months after initial infection

See Reference G: Monitoring the HIV-infected individual


TREATMENT OF HIV DISEASE

Three traditional strategies
These may be used alone or in combination. A particular drug may affect more than one area. Alpha interferon treats Kaposi's sarcoma. It can reduce the severity of the lesions, enhance the immune response and may have an antiviral effect as well.
1. Use of antiviral agents to combat HIV directly. These may be administered alone or in various combinations (given concurrently or alternated)
2. Prevention (prohylaxis) and/or treatment of the Opportunistic infections and cancers
3. Therapies that enhance the immune response and immune Based Therapies (IBT)

A fourth approach
4. The multifunctional approach (Complementary and/or alternative treatments.) The multifunctional approach to HIV/AIDS treatments involves the person living with HIV/AIDS utilizing a combination of:
a. prescribed drugs
b. over-the- counter drugs
c. Chinese herbs and procedures such as acupuncture
d. investigational drugs
e. nutritional approaches
f. attitudinal/lifestyle approaches
g. "unorthodox" treatments.

Problems and Considerations Associated With Administration of Drugs
1. Possible toxicity
a. side effects of an individual drug, e.g. AZT associated anemia and neuropathy; Neuropathy, pancreatitis and fulminant hepatic failure from ddC, ddI etc.
b. drug interactions or cross reactions
c. synergistic Vs antagonistic effects of drugs administered at the same time
2. Development of resistance to a particular drug
3. Availability (useability) of a particular drug in the body
4. Can pharmacologically active blood levels be maintained
5. Length of treatment required
6. Method of administration
7. When to begin administering a particular drug

Treatments and prophylaxis have been shown to be effective in reducing the number of annual deaths from AIDS. Even prior to the advent of the protease inhibitors, the death rate had begun to drop. With use of the protease inhibitors, the death rate in places like New York City has dropped by 50%. In some people, use of the protease inhibitors has resulted in the viral load being undetectable. There is hope that eventually HIV may be able to be cleared from the body. However, this has not yet occurred. Additionally, the protease inhibitors are not effective in all individuals. Even in those in whom the viral load has dropped, the immune system may or may not be combating the opportunistic infections seen in HIV disease/AIDS. There is great concern that resistance to these drugs may develop fairly rapidly. Nonetheless, the effectiveness of treatments has resulted in many changes in attitudes for people living with HIV disease. The phrase "Back to the future" has been used to describe the phenomenon that now there is more hope for there being one.


PHYSICAL LIMITATIONS
The degree of physical impairment can vary significantly with HIV disability depending on disease progression, secondary infections, HIV-related conditions and treatment side effects. When providing vocational rehabilitation services to HIV infected clients, it is important to understand each individual will respond to illness in a unique manner. Also it is important to know that a person living with HIV Disease may be very ill one day and feel fine the next.

In the HIV health care arena, physical status is measured using the Karnofsky performance scale when providing services to HIV infected clients. An individual is linked to appropriate in-home supportive services based on a functional performance of 60 or less. The Karnofsky Performance Tool can be a useful guideline to assess the physical abilities of any client.

Table 1.5 KARNOFSKY PERFORMANCE STATUS CRITERIA

100 Normal; no complaints
90 Able to carry on normal activity; minor signs or symptoms of disease.
80 Normal activity with effort; some signs or symptoms of disease.
70 Cares for self; unable to carry on normal activity or to do active work.
60 Requires occasional assistance, but is able to care for most of his needs.
50 Requires considerable assistance and frequent medical care.
40 Disabled; require special care and assistance.
30 Severely disabled; hospitalization is indicated although death not imminent.
20 Very sick; hospitalization necessary; active supportive treatment necessary.
10 Moribund; fatal processes progressing rapidly.
0 Dead

History and Medical Module 1

History and Medical Module 1

SYSTEM/Problem DRUG COMMON SIDE EFFECTS


History and Medical Module 1

History and Medical Module 1


History and Medical Module 1


History and Medical Module 1



REFERENCE MATERIALS for MEDICAL MODULE
A Scope and Impact of HIV Disease
B. CDC The First 500,000 cases
C History of HIV Disease
D. Clinical Manifestations: The Main OIs, Malignancies and Other Conditions Commonly Seen in HIV Disease
E. Drug Side Effects
F. Clinical Manifestations by Organ System
G Monitoring the HIV-infected individual
I Risk Reduction
H Glossary


REFERENCE A. Scope and Impact of HIV Disease
Worldwide: AIDS has been reported in over 150 countries. The current number of HIV-infected individuals is estimated at 22 million. By the turn of the century, 25-35 million are expected to be infected and President Yoweri Museveni of Uganda projects that by that time, 90% of the diagnosed AIDS cases will be in the developing world. The number of cases in the industrialized countries are expected to remain high through the mid 1990s and then level off (James Chin, World Health Organization (WHO)). Indeed, in the U.S., the number of AIDS cases has leveled off at about 60,000 per year. By the year 2000, it is anticipated that there will be 500,000 to 750,000 new cases of AIDS per year in sub-Saharan Africa, and more than 250,000 cases in Asia (WHO). Latin America is also expected to see dramatic increases.

Figure 1.10 Estimated Global Distribution

The proportions of male to female cases varies from place to place based on the strain of HIV seen and transmission patterns.

Economic impact: HIV infection usually infects people of childbearing age who support both the elderly and the young, and in many countries produce the food supply. The cost of decreased national productivity and the horrendous human costs are staggering Within the next decade in Africa, it is estimated that one in four farming families will suffer extreme labor shortages due to AIDS, resulting in serious food shortages.
Antonia Novello, U.S. Surgeon General in the Bush administrations, projects that there will be 10,000,000 children orphaned because of AIDS, by the year 2,000.

In the U.S., AIDS has been reported in all fifty states. The CDC estimates 800,000 to one million people are infected with HIV . As of June 30, 1996, a total of 548,102 persons with AIDS had been reported to the Centers for Disease Control and Prevention. 343,000 (62.5%) had been reported as having died (CDC) Reporting of AIDS and HIV-related deaths probably represents only 50-80% of the actual cases. Early in the epidemic, reporting was considerably less, as many individuals died with undiagnosed AIDS.

AIDS is the leading cause of death for all Americans between the ages of 25-44.
AIDS is the leading cause of death in men ages 25-44
AIDS is the fourth leading cause of death in women 15-44,/ 2nd in women ages 25-44
AIDS is a significant cause of Death in children
One death occurs every 12 minutes in the U.S.

Figure 1.11 Death Rates for Men

Figure 1.12 Death Rates for Women


In California as of 3-97 there had been 99,908 cases reported with 64,137 deaths
In San Francisco, as of 3-97 there had been 24,053 cases reported, with 16,718 deaths. These figures represent more deaths from AIDS in San Francisco than in all the U.S. wars to date.

HIV Infections in the U.S. as of 1993 in those 27-39 years of age
Men
One in 92 men
One in 139 white men
One in 33 African-American men
One in 60 Latino men
Women
One in 1,667 white women
One in 98 African -American women
One in 222 Latina Women



REFERENCE B. CDC The First 500,000 cases

Adapted from the November 24,1995 / Vol. 44 / No. 46

MORBIDITY AND MORTALITY
WEEKLY REPORT

Printed and distributed by the Massachusetts Medical society,
publishers of The New England Journal of Medicine



First 500,000 AIDS Cases - United States, 1995

As of October 31, 1995, a total of 501,310 persons with acquired immunodeficiency syndrome (AIDS) had been reported to CDC by state and territorial health departments; 311,381 (62%) had been reported as having died. The AIDS surveillance case definition was substantially expanded in late 1987 and again in 1993 to reflect increased knowledge of the natural history of human immunodeficiency virus (HIV) and to remain consistent with the clinical management of HIV disease (1,2). This report presents rates of reported AIDS cases for 1994 and describes the temporal changes in the characteristics of persons reported with AIDS during three periods corresponding to changes in the AIDS case definition--1981-1987, 1988-1992, and 1993-October 1995--and how this information can be used to plan local, state, and national prevention programs.†
Of the cumulative AIDS cases, 50,352 (10%) were reported during 1981-1987, 203,217 (41%) during 1988-1992, and 247,741 (49%) during 1993-October 1995. The proportion of AIDS cases among females increased from 8% of cases reported during 1981-1987 to 18% during 1993-October 1995 (Table 1). The proportion of cases among whites decreased from 60% to 43%, and the proportion among blacks and Hispanics increased from 25% to 38% and from 14% to 18%, respectively. During 1994, the rates per 100,000 population for blacks and Hispanics (101 and 51, respectively) were substantially higher than rates for whites (17), American Indians/Alaskan Natives (12), and Asians/Pacific Islanders (6).
The proportion of cases among persons who reported injecting-drug use increased from 17% during 1981-1987 to 27% during 1993-October 1995, and the proportion of cases attributed to heterosexual transmission increased from 3% to 10%. Cases among men who have sex with men decreased from 64% to 45%.
During 1994, the rates per 100,000 population for reported AIDS cases were 48 in the Northeast, 31 in the South, 29 in the West, and 13 in the Midwest.‡ However, during 1988-1992 and 1993-October 1995, the largest numbers of cases (65,926 and 86,462, respectively) were reported from the South, which also accounted for the largest proportionate increase of reported cases (31%). The proportionate increases in reported cases from 1988-1992 to 1993-October 1995 for the Midwest, Northeast, and West were 22%, 20%, and 15%, respectively.

_______________

† Single copies of this report will be available free until November 22, 1996, from the CDC National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD 20849-6003; telephone (800) 4585231 or (301) 217-0023.
‡ Northeast=Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; Midwest=lllinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; South=Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West=Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming.


TABLE 1. Number and percentage of persons with AIDS, by selected characteristics and period of report - United States, 1981-October 1995
1993-
1981-1987 1988-1992 October 1995 Cumulative
Characteristic No. (%) No. (%) No. (%) No. (%)
Sex
Male 46,317 (92.0) 177,807 (87.5) 204,356 (82.5) 428,480 (85.5)
Female 4,035 (8.0) 25,410 (12.5) 43,383 (17.5) 72,828 (14.5)
Age group (yrs)
0- 4 653 (1.3) 2,766 (1.4) 2,013 (0.8) 5,432 (1.1)
5-12 100 (0.2) 669 (0.3) 616 (0.2) 1,385 (0.3)
13-19 199 (0.4) 758 (0.4) 1,343 (0.5) 2,300 (0.5)
20-29 10,531 (20.9) 38,662 (19.0) 41,861 (16.9) 91,054 (18.2)
30-39 23,269 (46.2) 92,493 (45.5) 111,992 (45.3) 227,754 (45.4)
40-49 10,491 (20.8) 47,088 (23.1) 64,990 (26.2) 122,569 (24.4)
50-59 3,690 (7.3) 14,537 (7.2) 18,413 (7.5) 36,640 (7.3)
>60 1,419 (2.8) 6,244 (3.1) 6,513 (2.6) 14,176 (2.8)
Race/Ethnicity
White, non-Hispanic 30,104 (59.8) 102,551 (50.5) 105,516 (42.6) 238,171 (47.5)
Black, non-Hispanic 12,794 (25.4) 63,319 (31.2) 94,158 (38.0) 170,271 (34.0)
Hispanic† 7,039 (14.0) 35,213 (17.3) 45,135 (18.2) 87,387 (17.4)
Asian/Pacific
Islander 309 (0.6) 1,339 (0.7) 1,809 (0.7) 3,457 (0.7)
American Indian/
Alaskan Native 67 (0.1) 433 (0.2) 783 (0.3) 1,283 (0.3)
HIV-exposure category*
Men who have sex
with men 32,246 (64.0) 110,934 (54.6) 111,257 (44.9) 254,437 (50.8)
Injecting-drug use 8,639 (17.2) 49,093 (24.2) 67,708 (27.3) 125,440 (25.0)
Men who have sex
with men and
inject drugs 4,193 (8.3) 14,252 (7.0) 13,984 (5.6) 32,429 (6.5)
Hemophilia 505 (1.0) 1,744 (0.9) 2,009 (0.8) 4,258 (0.8)
Heterosexual contact 1,248 (2.5) 12,335 (6.1) 24,958 (10.1) 38,541 (7.7)
Transfusion recipients 1,285 (2.6) 3,894 (1.9) 2,521 (1.0) 7,700 (1.6)
Perinatal transmission 608 (1.2) 3,084 (1.5) 2,432 (1.0) 6,124 (1.2)
No risk reported 1,628 (3.2) 7,881 (3.9) 22,872 (9.2) 32,381 (6.4)
Region‡
Northeast 19,544 (38.8) 62,282 (30.6) 74,769 (30.2) 156,595 (31.2)
Midwest 3,770 (7.5) 20,352 (10.0) 24,914 (10.1) 49,036 (9.8)
South 12,960 (25.7) 65,926 (32.4) 86,462 (34.9) 165,348 (33.0)
West 13,550 (26.9) 46,675 (23.0) 53,729 (21.7) 113,954 (22.7)
U.S. territories 516 (1.0) 7,889 (3.9) 7,566 (3.1) 15,971 (3.2)
Vital status
Living 2,779 5.5) 32,144 (15.8) 155,006 (62.6) 189,929 (37.9)
Deceased 47,573 (94.5) 171,073 (84.2) 92,735 (37.4) 311,381 (62.1)

Totals§ 50,352 (100) 203,217 (100) 247,741 (100) 501,310 (100)

† Persons of Hispanic origin may be of any race.
* HIV exposure category is hierarchical. A person who has engaged in a number of risk behaviors will be placed in the first category found on the list. A person who has used IV drugs, even if they have not shared needles, would be placed in the IV drug category. Transmission might have occured through intercourse.
* Woman-to-woman transmission is not a category. The CDC definition of a lesbian is a woman who has not had sex with a man since 1977.
‡ Northeast=Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; Midwest=lllinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; South=Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia , Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West=Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming,
§ Includes persons for whom sex, race/ethnicity, or region are missing.

During 1993-October 1995 in the South and Midwest, higher proportions of cases among adolescents and young adults (aged 13-29 years) occurred in small (50,000-499,999 population) metropolitan statistical areas (MSAs) and non-MSAs (rural areas) (27% and 24%, respectively) compared with 9% in the Northeast and 1 1% in the West. During this time period, among cases in adolescent and young adult men who have sex with men, 25% of 8481 cases in the South occurred in persons who resided in small MSAs and rural areas, 21% of 2870 in the Midwest, 9% of 3311 in the Northeast, and 9% of 5706 in the West. Among adolescent and young adult injecting drug users, 30% of 531 cases in the Midwest occurred among persons residing in small MSAs and rural areas, 23% of 2370 in the South, 17% of 930 in the West, and 8% of 3304 in the Northeast. The proportion of cases among adolescents and young adults residing in small MSAs and rural areas that resulted from heterosexual transmission was highest in the South (32% of 2842), followed by the Midwest (22% of 678), the West (18% of 691), and the Northeast (7% of 1745).
During 1993-October 1995, most AIDS cases among adolescent and young adult men who have sex with men occurred among whites in all four regions (Midwest, 57%; West, 56%; South, 49%; and Northeast, 42%). Black adolescent and young adult men who have sex with men accounted for 39% of cases in the South, 37% in the Midwest, 36% in the Northeast, and 14% in the West. These proportions were higher than those for cases among black adolescent and young adult men who have sex with men reported during 1988-1992 (South, 31%; Midwest, 30%; Northeast, 31%; and West, 12%).
Reported by: Div of HIV/AIDS Prevention, National Center for Prevention Svcs, CDC.
Editorial Note: The World Health Organization estimates that 18 million adults and 1.5 million children have been infected with HIV, resulting in approximately 4.5 million AIDS cases worldwide (3). The theme for the 1995 World AIDS Day (December 1) is "Shared Rights, Shared Responsibilities." The findings in this report document both the magnitude and evolving nature of the AIDS epidemic in the United States, and underscore that HIV-prevention programs must be planned and implemented collaboratively by persons with diverse skills, training, and experience.
In addition to describing the overall magnitude of the epidemic-approximately one half million cases, nearly half of which have been reported since 1993-this report highlights changes in the epidemiologic patterns during 1993-October 1995 compared with those during earlier periods. In particular, although men who have sex with men continue to account for the largest proportion of cases, the AIDS epidemic is increasing more rapidly among injecting-drug users and persons infected through heterosexual contact with a partner at risk for or known to have HIV infection or AIDS (4,5). The increase in AIDS cases resulting from heterosexual transmission also is reflected in the increase in cases reported among women. The proportions of AIDS cases reported during 1993-October 1995 that are attributed to these risk behaviors will increase as records of persons who were reported initially without risk are reviewed and the risk is identified (6). Geographic patterns also have changed, as reflected by increases occurring among persons in the South. Finally, regardless of transmission mode or region, the epidemic continues to affect blacks and Hispanics disproportionately.
Although the AIDS epidemic in the United States was recognized initially in the Northeast and West (7), and rates remain highest in the Northeast, the findings from AIDS surveillance document that the greatest proportionate increases in the HIV epidemic have occurred in the South and Midwest-areas that account for the largest proportion of the total U.S. population. These regional variations, especially in adolescents and young adults, underscore the importance of developing HIV-prevention programs based on local trends in the epidemiology of HIV transmission. In the South and Midwest, more detailed characterization of the epidemiologic patterns in small cities and rural areas is particularly important for developing effective region wide prevention programs.
The disproportionate impact of the epidemic among racial/ethnic minorities is reflected by rates of reported AIDS cases that are six and three times higher for blacks and Hispanics, respectively, than for whites. Rates for HIV infection and the proportions of men who have sex with men and injecting-drug users with AIDS who are black and Hispanic also vary substantially by region (8). For example, Hispanics account for lower proportions of reported cases of AIDS among adolescents and young adult men who have sex with men in the Midwest and South than in the Northeast and West. Because race and ethnicity are not risk factors for HIV transmission, programs to prevent HIV transmission among racial/ethnic minorities should be based on underlying social, economic, and cultural factors that influence risk behaviors (8).
Because of the regional and local variations in the AIDS epidemic in the United States, HIV-prevention efforts must be directed at the local level. In 1993, a CDC advisory committee review of HIV-prevention programs emphasized the importance of 1) enhancing the capacity of local and state agencies to collect and analyze information relevant to the specific and unique aspects of HIV transmission in their communities, 2) strengthening the behavioral and social science bases of HIV-prevention activities, and 3) ensuring that HIV-prevention strategies and interventions reflect the preferences and needs of the affected communities for whom they are intended (9). As a result, in 1994, CDC initiated the HIV Prevention Community Planning process (10 ) that has provided resources for collaboration between health departments and planning groups that are representative of the local communities. These resources facilitate HIV-prevention programs that are based on scientific data (including data from HIV/AIDS surveillance, seroprevalence surveys, vital statistics, and behavioral research) and knowledge of the community norms and practices. This approach is consistent with the focus of World AIDS Day and emphasizes the necessity of shared participation in HIV-prevention planning and program implementation.

References
1. CDC. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR 1987;36(suppl 1).
2. CDC. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41(no. RR-17).
3. World Health Organization. The current global situation of the HIV/AIDS pandemic. Geneva, Switzerland: World Health Organization, 1995.
4. CDC. Update: trends in AIDS among men who have sex with men-United States, 1989-1994. MMWR 1995;44:401-4.
5. CDC. Update: trends in AIDS diagnosis and reporting under the expanded surveillance definition for adolescents and adults-United States, 1993. MMWR 1994;43:826-31.
6. CDC. HIV/AIDS surveillance report. Atlanta: US Department of Health and Human Services, Public Health Service, CDC, 1995:3-4,30-4. (Vol 7, no. 1).
7. CDC. Follow-up on Kaposi's sarcoma and Pneumocystis pneumonia. MMWR 30:409-10.
8. CDC. AIDS among racial/ethnic minorities-United States, 1993. MMWR 1994;43:644-7,653-5.
9. CDC. External review of CDCs HIV prevention strategies by the CDC Advisory Committee on the Prevention of HIV Infection. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, CDC, 1994.
10. Valdiserri RO, Aultman TV, Curran JW. Community planning: a national strategy to improve HIV prevention programs. J Community Health 1995;20:87-100.


REFERENCE C. History of HIV Disease
In the spring of 1981 the United States Public Health Service Centers for Disease Control (CDC) began receiving reports of cases of Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma (KS) in previously healthy young gay men in Los Angeles, New York and San Francisco The CDC is responsible for monitoring infectious diseases in the U.S. While the fungus Pneumocysitis Carinii is widespread in the lungs of U.S. residents, it does not usually cause pneumonia. PCP is usually found only in people whose immune systems are not functioning properly, such as those who lack immune response because of genetic diseases and those who are receiving cancer chemotherapy or immunosuppressive therapy for organ transplants. Kaposi's sarcoma (KS) is usually seen in older men of Mediterranean heritage, and in whom this cancer of the walls of blood vessels is not a fatal disease. It soon became apparent that these young men were also unable to mount an immune response against other viral, bacterial and parasitic infections (the opportunistic infections) and a large percentage of them were dying. In December 1981, reports in the New England Journal of Medicine demonstrated that the original individuals reported to the CDC had decreased counts of specialized white blood cells, the T lymphocytes. The initial belief was that the immune system dysfunction that permitted the development of these opportunistic infections (OIs) was somehow related to the gay lifestyle. Use of inhalant drugs, treatment for a number of sexually transmitted diseases, multiple sexual partners, and antigen overload from sperm introduced into the rectum in anal sex, were part of the history of many of the patients being seen with this new phenomenon. All of these had been shown to be immunosuppressive. This is why the term Gay Related Immune Deficiency (GRID) was the name first applied. The CDC began its epidemiological investigation. Epidemiology is the science concerned with defining and explaining the interrelationships of factors that determine disease frequency and distribution. This is based on statistical evidence, not on clinical or laboratory experimentation. In order to monitor the disease, the CDC asked in 1982 that all cases be reported.

Within a short period of time there were others, besides gay men, who were suffering from conditions associated with immune system compromise. These included :
• intravenous (IV) drug users
• recent Haitian immigrants to the U.S.
• blood transfusion recipients
• infants of mothers with the disease
• hemophiliacs,
• sexual partners of those with the disease.

Cases were also reported from Europe and Africa. At this point it became apparent that some infectious agent was involved. In early 1982 the CDC recommended that the term AIDS (Acquired Immune Deficiency Syndrome) be used to describe this disease phenomenon which appeared to be a collection of symptoms associated with an immune-system deficiency that was not inborn or imposed but somehow acquired. Initially the only two diseases recognized as an AIDS diagnosis were PCP and KS. Once it became clearly established that AIDS was caused by an infectious agent, the definition of AIDS began to be expanded to include other illnesses besides the original ones

AIDS was named before the cause and course of the disease were known.
By 1983 it was quite apparent that there were people who did not have PCP, Kaposi's sarcoma or any of the recognized opportunistic infections (or cancers associated with the syndrome) who were also showing signs of illness. These illnesses included:
• unexplained fevers
• weight loss
• lymphadenopathy (swollen glands over a long period of time)
• persistent diarrhea
• neurological impairment

The term ARC (AIDS Related Complex, or AIDS Related Conditions) began to be used to describe a multitude of conditions that were not listed by the CDC to define AIDS.

AIDS Related Complex (A.R.C.) = A set of conditions associated with HIV infection. There is impairment of health, but the condition is not recognized by the Centers for Disease Control as constituting an AIDS diagnosis. This term is used infrequently now that the term HIV infection (or HIV disease) is used.

Unfortunately, it was not only people who were diagnosed as having AIDS who were dying, but people who had ARC as well. Because only those with a diagnosis of AIDS were counted in the statistics being gathered by the CDC, those deaths due to ARC were not counted.

In 1983 the cause of AIDS was ascribed to a virus eventually named HIV. By 1984, laboratory evidence of HIV infection, the presence of antibodies in the bloodstream which are produced by the body against HIV, had been established. By the spring of 1985 a test for these antibodies had been developed and licensed. The test was designed as a method of screening the blood supply.

In 1986 the CDC introduced a "Classification of Disease" which acknowledged the existence of HIV infection or HIV Disease as a medical entity .

The official "AIDS diagnosis" still did not include people who were dying because of HIV infection, who had neurological involvement or Wasting Syndrome. It also did not reflect HIV associated illness in women, such as cervical cancer.

In 1987 the CDC defined new criteria for establishing an AIDS diagnosis. This case definition of AIDS for reporting purposes is a complicated formula based on antibody status, and presumptive or positive diagnosis of all of the illness that had previously constituted an AIDS diagnosis.

It added :
• neurological involvement
• wasting syndrome.

Even this broadening of the definition still did not adequately reflect the scope of either those infected or those who showed physiological impairment. Women's clinical manifestations were still ignored in the diagnostic criteria. In 1991 the CDC announced plans to broaden the definition of AIDS to include a CD4 count of less than 200. The initial date of instituting the diagnostic criteria was moved from January to April and then postponed from April 1992 to January 1, 1993. This new revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults corresponded closely with a change in the name of the Centers for Disease Control to the Centers for Disease Control and Prevention with "CDC" still to be used as the acronym (OCT. 27, 1992).


REFERENCE D. Clinical Manifestations;: The Main OIs, Malignancies and Other Conditions Commonly Seen in HIV Disease

Categories of Opportunistic Infections (OIs) Associated with HIV Disease
1. Protozoal Infections. Protozoa are the simplest, often one-celled, animals
OI RESULT(S) OF INFECTION VECTORS
Toxoplasmosis encephalitis, pneumonia, orchitis (inflammation of testes) cats, rodents, carnivores
Cryptosporidiosis severe diarrhea, respiratory involvement farm animals
Isosporiasis diarrhea, can be disseminated throughout the body
Microsporidium diarrhea
Acanthamoeba sinus and skin infections

2. Viral Infections. Virus = simple, minute parasitic organism that cannot reproduce outside of a living cell. They can only be seen with an electron microscope. These may also act directly to lower the immune response.


OI AREA(S) INFECTED DISEASE(S) SEEN
Herpes simplex virus I and II genitals, mucous membranes lesions
Cytomegalovirus disseminated, adrenal glands, GI tract, CNS, eyes (blindness) CMV Retinitis -sight impairment /blindness

CMV pneumonia
Epstein barr virus CNS, mouth, lungs Lymphoma, Oral hairy Leukoplakia, Lymphoid interstitial pneumonia in children
Papovaviruses
1. Human Papilloma virus (warts)
2. JC papovavirus
1. Cervix and anus
1. cancer

2. PML


3. Fungal Infections Fungus = a plantlike organism
OI AREA(S) INFECTED VECTOR(S)
Pneumocystis carinii (pneumonia)
Most common cause of death in AIDS lungs
Candidiasis (Candida albicans) mouth, esophagus, vagina, disseminated
Cryptococcosis meningitis pigeons
Histoplasmosis disseminated birds, bats
Coccidiomycosis
(San Joaquin Valley Fever) lungs, disseminated soil spores
Superficial mycoses skin
Aspergilliosis (Strawberry mold) lungs

4. Bacterial Infections (commonly found in HIV-infected children) Bacteria = microorganisms of three forms: spherical or ovoid; rod shaped; spiral.
OI AREA(S) INFECTED
Staphylococcus aureus
Hemophilus influenzae
Streptococcus pneumoniae
Salmonella (non-typhoid)
Nocardiosis pulmonary, skin and brain abscesses
Legionella pneumonophilia
Rhodococcus equii
Listeria monocytogenes

5. Mycobacteria = rod shaped, gram positive acid-fast bacteria
OI AREA(S) EFFECTED VECTOR(S)
Mycobacterium tuberculosis disseminated, pulmonary, CNS humans
Mycobacterium avium birds
Mycobacterium Kansii

6. Cancers that may be caused by an infectious organism.
CANCER CAUSATIVE AGENT
Kaposi's Sarcoma HHV-8
Lymphoma EBV
Cervical cancer HIV + HPV
Anal cancer HIV + HPV


AIDS DEMENTIA COMPLEX see Encephalopathy

ANAL CANCER see Malignancies

ASPERGILIOSIS (fungus which is commonly found on strawberries):
While common in immunocompromised patients this has been rare in HIV disease, although the number of cases is increasing. Pulmonary infection is sometimes mistaken on X-ray for tuberculosis. It usually follows corticosteroid use, neutropenia, pneumonia due to other organisms, marijuana smoking(?), or the use of broad spectrum antibiotics(?). The disease may be in the lungs and bronchi, or invasive and disseminated to other organs.
Symptoms include: breathlessness, cough, fever, night sweats, and occasionally chest pain.
Treatment includes amphotericin B and/or itroconazole.

AUTOIMMUNE DISORDERS
Rheumatological manifestations
Autoimmune hemolytic anemia

ANEMIA is a decrease in the number of circulating red blood cells available for oxygenation.
Causes
Medications such as AZT and Ganciclovir
Deficiencies in B12 and Folate
Mycobacterium avium (MAC)
HIV - Chronic disease
Occult blood loss
Signs and symptoms
Hemoglobin £ 8.0; Hematocrit £ 25, Pallor, Increased fatigue, Difficulty breathing, Weakness, Increased heart rate, Dizziness

COAGULATION DISORDERS (increased bleeding or inappropriate clotting)
a. Idiopathic Thrombocytopenic Purpura (ITP) Involves a decrease in the number of platelet cells. Platelets help blood coagulation, hemostasis and blood thrombus formation. When a small blood vessel is injured, platelets adhere to each other at the edges of the injury and form a plug which covers the area. With decreased platelets, bruisability (hemorrhages into the skin) increases. In women, menstrual flow increases. AZT use reveals a beneficial effect on the platelet count at 1,000 mg per day.

b. Thrombocytopenia is a decrease in the number of platelets available for hemostasis, thereby increasing the risk of bleeding.
Causes
Medications, Infections with bone marrow involvement (MAC)
Neoplasms (e.g., lymphoma)
Autoimmune response
Signs And Symptoms
Decreasing platelet count < 100,000 cells/mm3 with increased risk of bleeding when count falls below 50,000 cells/mm3
Bleeding gums, increased bruising, rectal bleeding, bloody stools, epistaxis

c. Increased risk of thrombosis (a blood clot within the vascular system). Endothelial cells line the blood vessels. They synthesize many substances involved in coagulation. They can express MHC class II, act as antigen-presenting cells, produce interleukin-1, and promote interleukin-2 secretion by T-cells. Endothelial cell function is impaired in HIV infection either directly by HIV (?) or perhaps by infection with CMV, or by cytokines (IL-1 of TNF-a). The effect is increased possibility of inappropriate coagulation resulting in thrombosis.

CANDIDA ALBICANS (candidiasis) This is the most common fungal infection seen in HIV disease. If in the esophagus, bronchi, trachea or lungs, it qualifies as AIDS diagnosis. Although common in HIV-infected women, severe vaginal infections do not yet qualify for an AIDS diagnosis. In the mouth it is more indicative of clinical disease progression. This is also known as thrush. Candida often survives in the vagina and around the corona of the penis. It does not necessarily cause difficulties. Disruption of the vaginal environment may cause limited infections in the vagina. Decreased immune function leads to more pronounced infection. Infants may be exposed to Candida during birth and exhibit thrush. As well as there being mucosal and skin infections, it is important to know that there can be invasive deep tissue infections, including in the gastrointestinal tract and lungs, that may go undiagnosed. Saliva of HIV-infected people has decreased ability to protect against fungal diseases in the mouth.
Symptoms
White or grayish patches in the mouth or on the tongue
Painful mouth, difficulty swallowing
Vaginal discharge, itching and discomfort with vaginal candidiasis
Skin lesions
Treatments
Fluconazole is effective against Candida infections, but there are increasing reports of resistance to fluconazole and the other azole drugs. Amphotericin B is useful.

CERVICAL CANCER see Malignancies

COCCIDIOMYCOSIS This is also known as "Valley Fever." It is a fungal infection of the lungs. In the lungs it is not an AIDS diagnosis. Found in a disseminated form in extra pulmonary sites, it constitutes an AIDS diagnosis. The spores of the organism are in soil and are inhaled, resulting in lung infection. The spore is commonly found in the soil of the San Joaquin Valley in California. The 1994 earthquake in Los Angeles apparently stirred up soil containing this fungus resulting in new cases of Coccidiomycosis in Ventura county (adjacent to LA.)

CONSTITUTIONAL DISEASE (HIV Wasting Syndrome). Defined as:
1. fever persisting for more than one month
2. involuntary weight loss greater than 10% of baseline
3. diarrhea persisting more than 30 days (2 stools a day)
4. and the absence of conditions other than HIV infection to explain the findings.
This is also referred to as "HIV Wasting Syndrome (WS) and "Slim disease." This primarily involves loss of lean body mass (muscle) as well as loss of fat.

Reasons why individuals infected with HIV may be losing weight:
1. HIV infection of cells causes an auto-immune response
2. Tumor necrosis factor may result in cachexia.(wasting)
3. HIV may directly affect the tissue of the gastro-intestinal tissue leading to acute esophageal ulcers, malabsorptive diarrhea and inflammation of the colon (colitis). Even in very early stages of HIV disease inflammation of the intestines has been observed. As disease progresses, problems with metabolism and absorption increase while body mass decreases. There is poor absorption of sugars.
4. A number of the organisms causing the OIs result in diarrhea which leads to weight loss. (this would not be constitutional disease or wasting)
5. Kaposi's Sarcoma may invade the intestinal tract.
6. Oral manifestations of HIV disease may prevent food intake resulting in marked weight loss. Oral/esophageal lesions: (Thrush, Hairy Leukoplakia, ulcerations, K.S. lesions, Herpes Simplex lesions, gingivitis, HPV) cause discomfort associated with eating.
7. Swollen glands may cause discomfort when eating.
8. Adrenal insufficiency results in decreased stomach acids and digestion
9. Food may taste differently in HIV disease (dysgeusia)
10. Conditions associated with HIV infection may lead to malnutrition:
a. Dementia: forget or refuse to eat
b. Anxiety: person doesn't stop to eat.
c. Depression: lack of interest in food
d. Appetite may be impaired (anorexia)
e. Nausea and vomiting may be present either because of OIs, WS or drug treatments.
f. Decreased physical ability may make shopping or preparing of food difficult or impossible
g. Lack of money to buy food may be a problem
h. Weight loss may require an increase in caloric intake.
i. Malnutrition decreases immune system function.
j. Poor diet affects mood and energy levels. Poor diet can lead to depression which in turn can lead to lack of appetite.
11. Physicians receive very little nutritional education in medical school and have tended to neglect this area in medical practice, other than dealing with obesity issues. Even regarding heart disease and high cholesterol, physicians may prescribe medication rather than offer diet modification plans.

CRYPTOCOCCAL INFECTIONS (fungus) A fungal infection which affects the Central Nervous System (CNS), lungs, peritoneal cavity and skin. Outside the lungs it constitutes an AIDS diagnosis. Cryptococci are found frequently in soil, particularly where pigeons live. It may be contracted by inhalation of aerosolized droplets which become airborne. They enter the lungs and spread to other organs such as the liver, bone and skin where they cause damage. In the brain they cause meningitis. Lung infections are rare, but can be found in people whose immune systems are suppressed. No person to person transmission of this disease has ever been reported. In those with AIDS, this is most commonly found in IV drug users, African-Americans, Haitians, and geographically in New Jersey.

The most common CNS disorder is Cryptococcal meningitis. Approximately 6-12% of HIV positive individuals are diagnosed with Cryptococcal meningitis. The organism causes an inflammation of the meninges, the covering of the brain and spinal cord. It usually develops slowly over weeks or months and is accompanied by fever, headache and malaise. Stiffness of the neck and aversion to sunlight occurs in about one-third of patients. Mental state changes have been reported in 20% of cases. Diagnosis is made by analysis of cerebral spinal fluid obtained from a spinal tap. 50-75% of people respond to anti-fungal therapy.
Symptoms
Fever Headache
Photophobia Visual changes
Slurred Speech Hearing Loss
Decreased coordination Confusion/lethargy
Treatment
Amphotericin B is more effective than fluconazole for initial treatment.
Chlotrimazole used.
Fluconazole is more effective for maintenance therapy.
Itraconazole is effective in preventing disseminated cryptococcal disease

CRYPTOSPORIDIOSIS (protozoa): commonly found in farm animals. This organism causes severe long lasting diarrhea. To qualify for an AIDS diagnosis, the diarrhea must have lasted more than 30 days. Diarrhea of many quarts of fluid per day is common with this infection. Cryptosporidium oocysts are becoming more common in drinking water.
Symptoms
Severe watery diarrhea Dehydration
Bloating Fatigue
Anorexia Fever
Treatment: There are no approved treatments for cryptosporidiosis, however, Azithromycin at high doses is effective in some people. IGX may be helpful in HIV+ individuals. Letrazuril destroys the eggs but does not always alleviate symptoms of the disease. Paromycin (Humatin) is effective in continuous treatment. In areas where cryptosporidium is present in the water supply, boiling the water before drinking is advisable.

CYTOMEGALOVIRUS INFECTIONS (CMV): If in the liver, spleen or lymph nodes, CMV does not constitute an AIDS diagnosis. If elsewhere, or in the retina of the eye, it does. A member of the Herpes Virus family, CMV causes hepatitis, pneumonia, encephalitis, inflammation of the intestinal tract (colitis), adrenalitis and CMV retinitis which can result in blindness. The infection may be latent since childhood and then reactivated with immunodeficiency. In the past 20 years, 800,000 children have been infected with CMV in-utero. CMV may be involved in the effect HIV has on certain tissue and is being investigated as a co-factor in disease manifestation and progression. CMV may also help disrupt the endocrine system. For instance, the adrenal gland is infected with HIV in 33-89% of people who die of AIDS. Cytomegalovirus (CMV) is a virus that becomes reactivated. Depending on the socioeconomic condition of the population, the prevalence of antibodies ranges from 40-100% in adults.
Symptoms
Eye Disease
Floating spots before the eyes
Hazy vision
Blurred or missing areas of vision
Digestive Disease
Diarrhea Loss of appetite
Fever Blood
Stomach cramps Weight loss
Painful swallowing Pain in center of chest
Treatment
Ganciclovir, and a combination of ganciclovir and foscarnet are effective in both CMV retinitis and in CMV gastrointestinal disease. Intraocular injection of foscarnet is becoming more common and appears to be quite effective. Anti-CMV Human Immunoglobulin enhances immune response and prevents a relapse of CMV disease.

DRUG SIDE EFFECTS See Reference Section E.
Many of the drugs given to people living with HIV Disease cause severely debilitating side effects. In some cases the side effects may be worse then the symptoms of the illness.

ENCEPHALOPATHY
Neurologic disease. (A prime example of the complexity of HIV disease.)(AIDS Health Project)
Defined as one or more of the following:
1. dementia (insanity)
2. myelopathy (muscle weakness)
3. peripheral neuropathy (problems with the peripheral nerves--hands feet etc.)
4. and the absence of conditions other than HIV infection to explain the findings.

HIV associated dementia is a neurobehavioral deficit that is a common neurological complication of late-stage disease. The tissue changes in affected individuals appears to involve the white matter in the brain, the spinal cord, and subcortical gray matter with significant damage to neurons.

There are seven possible causes of the phenomenon of neurological disease.
1. AIDS Dementia Complex (ADC)
a. Direct effects of HIV infection on brain tissue
b. Indirect effects of immune system components or toxins produced by immune system cells on brain tissue.
2. Opportunistic infections of the brain associated with immune suppression.
3. Brain cancer (lymphomas) associated with immune suppression.
4. Nutritional disorders; metabolic disorders
5. Drug use. (recreational or the side effects of medication)
6. Cerebrovascular problems: infarction, hemorrhage, vasculitis
7. Psychological factors
Professionals should consider all the above for effective treatment.

1. AIDS Dementia Complex (ADC).
Direct and Indirect effects of the virus: HIV enters the brain shortly after infection. Infected macrophages are found in the brain as well, and HIV can multiply slowly within the macrophages. Both viral particles and macrophages can cross the blood brain barrier (a tightly linked group of cells which prevents many things from entering the brain) . The macrophages are described as Trojan horses carrying the virus into the brain. Several brain tissues and cells can become infected, including the glial cells. HIV is harbored in the brain in these cells. Cerebral spinal fluid (CSF) contains both infected cells and viral particles as well. HIV replication within the CNS (the brain and spinal cord) can lead to encephalitis accompanied by neuropsychiatric symptoms, brain atrophy and demyelinization of nerves. (The myelin sheath surrounds the nerve axons and speeds the transmission of the signals they carry. Destruction of the myelin sheath disrupts nerve function.)

AIDS Dementia Complex is the direct result of HIV infection and the immune response to the infection. It is one of the most insidious forms of neurological dysfunction that affects people with AIDS. The dementia complex that is related to HIV infection includes not only cognitive problems and behavioral complications (most notably withdrawal) but psycho motor retardation (essentially just a slowing down) and motor problems as well. HIV may destroy up to 38% of the brain cells of people with AIDS related dementia without inflammation. The loss appears often in the frontal lobe which helps control movement and higher mental processes, such as learning and abstract thought.

ADC Symptoms
Cognitive (cognition=to know): difficulties with concentration and memory, a general slowing of mental functioning and often personality changes; difficulty in completing daily tasks.; judgment, concentration, calculation and constructional abilities may be impaired; anosognosia (not to know that you don't know). The person may not be "Himself," or isn't as quick or witty.

Behavioral symptoms include social withdrawal and apathy; occasionally agitated and psychotic behavior may also appear. Personality changes are seen early. (A neat person may become sloppy, or neater--can't tolerate deviations.)

Motor problems can include difficulty with balance, clumsiness and leg weakness. Motor problems include unsteady gait, ataxia, peripheral neuropathies (burning of the hands and feet), probably related to neuroleukin problem &/or to neuromuscular problems. These tend to be progressive and deteriorating.
Myopathy (weak, painful, atrophied muscles) is often seen in HIV disease.

In the course of the illness more than 65% of patients exhibit overt neurological involvement and even more exhibit abnormalities on neurological tests.

At autopsy 80-90% of patients show neuropathy and brain lesions are found in at least 75% of those who have died from HIV infection.

Once clinical symptoms appear, a progressive decline in function occurs. The late stages of ADC often include: global dementia, often with little or no ability or willingness to speak. Multiple neurological abnormalities including bowel and bladder incontinence; and an overall vegetative state requiring total bed care. Consciousness is usually preserved although the patient may lie in bed, stare vacantly and have little social involvement with his or her caretakers. The same phenomenon occurs in children with them never reaching, or loss of, developmental milestones (when they roll over, sit up, crawl, stand etc.). They may develop to the point where they can lift their heads up, but then they lose that.
While the extent of ADC remains unclear, estimates are that approximately one-third of AIDS patients will develop moderate to severe dementia; one-quarter, mild dementia. As infection progresses, as many as two-thirds of AIDS patients may develop some signs of dementia, though these signs may not always be clinically apparent.

Diagnosis of ADC includes a positive HIV antibody test; negative tests for the other more common opportunistic infections; and neuropsychological tests.

Treatment of ADC
A treatment must cross the blood brain barrier to be effective--AZT does so and significantly decreases neurological symptoms.

2. Opportunistic infections
a. The most common Cryptococcal meningitis.
b. Toxoplasmosis gondii
c. Progressive Multifocal Leukoencephalopathy (PML)
d. Other infections which include: Cytomegalovirus; Herpes simplex virus I & II; Herpes zoster; Candida albicans; Histoplasma; Aspergillis; Coccdiodes; Acremonium alabamensis, Rhizopus; MAI; M. tuberculosis; M. Kansaii; Listeria; Nocardia.
e. Treponema pallidum (Neurosyphilis in Tertiary stage):

3. Cancers
a. Primary Lymphoma involve rare tumors that most commonly occur in people with suppressed immune systems.
b. There may also be metastatic systemic lymphoma.
c. There may also be Metastatic Kaposi's sarcoma.

Symptoms include disordered consciousness or cognition, hemiparesis (weakness in half the body)headaches, seizures and incontinence.

Diagnosis is made by CT scan, although the appearance of the tumors can be confused with toxoplasmosis lesions.
Treatment consists of chemotherapy and radiation therapy is the only treatment available and response to treatment is poor. The average survival time is two months.

4. Nutritional disorders
People who are not eating well or who have disruption of metabolism may also have neurological problems.

5. Drug use
a. Recreational drugs can change neurological functioning or behavior
b. Medications given for conditions associated with HIV disease or as antivirals often have side effects that alter neurological functioning, muscle activity and behavior.
6. Cerebrovascular problems may be associated with Injecting drug use and or complications of cancer and opportunistic infections.

7. Psychological effects
People dealing with HIV disease may initially respond to diagnosis of AIDS by regressing and transiently functioning at a psychologically less mature level than they might have prior to illness. They may also suffer post-traumatic stress symptoms, including periods of emotional numbing alternating with flooding of feelings. People often respond in this manner to catastrophic events.

AIDS brings specific stresses. It is intimately associated with socially stigmatized behaviors: male homosexual behavior (and homosexuality in general) and IV drug use are considered "sinful" by many. Homophobia abounds in our society. Sexuality itself is not dealt with well by society in general, and people often feel guilty when contracting a sexually transmitted disease. There is also a history of viewing the ill as somehow having done something wrong. Because AIDS is infectious and, at this point, incurable, it often excites rational and irrational fears in the public. It may cost an infected person the loss of a job or housing or family. It is hard to find knowledgeable health care providers who are willing to care for someone who is infected.
Signs and Symptoms
People may exhibit some of the following behaviors.
Early issues when first diagnosed include:
a. denial
b. the need for emotional, financial and social support, possibly impairs self-esteem
c. fear of contamination, treatment issues
d. fear of rejection by family and friends
e. feelings of guilt and self blame over previous lifestyle--illness seen as retribution
f. grief over lifestyle changes (is there sex after diagnosis?).
g. excessive concern with body symptoms
Mid-stage issues include:
a. loss of hope and emotional exhaustion
b. more detailed grief work (anticipating and mourning the loss of important people and objects)
c. extent of treatment; pain control
d. unfinished business- life review; putting one's affairs in order
Terminal care concerns include:
a. adequate pain control
b. dealing with family and friends
c. seeing to it that personal wishes are respected

Depression is common when having to deal with these issues. It is the most common reason for psychiatric consultation in HIV patients at San Francisco General Hospital. It accounted for one fourth of the psychiatric hospitalizations of HIV-infected patients at San Francisco General over a 2 to 3 year period. Suicidal thoughts are common. They are often an expression of the wish to exert some control over one's fate. It may be hard to differentiate between clinical depression and other HIV associated neurological effects (many symptoms overlap). Several clinical points may be helpful. Apathy should not be mistaken for depression. People who are depressed reach out emotionally and communicate affective pain. If an interviewer find that s/he feels sad and depressed after working with a client, rather than emotionally flat, depression is a likely diagnosis. Additionally, people who are depressed often have a history of depression. Thirdly, if cognitive problems progress AIDS Dementia Complex (ADC) should be suspected. Fourthly, it is important to recognize that ADC and depression can coexist. Depression may be treated with anti-depressants. The use of support groups can be very helpful.
The use of Fluoxetine seems very effective in treating the major depression associated with HIV disease.

Note: Sleep disturbances are also common in people living with HIV Disease

ENDOCRINE SYSTEM DYSFUNCTION
The endocrine system produces hormones that are involved in most body functions. The adrenal glands, thyroid, energy metabolism, testes (women haven't been studied), calcium metabolism and pancreas may be affected. These effects may be caused by the virus, infections (CMV is often found in the adrenals and pancreas on autopsy), cancer, hemorrhage, nonspecific inflammation, cytokines, or drugs given for treatment.

EPSTEIN BARR VIRUS INFECTION causes Burkitt's lymphoma, central nervous system lymphoma, and oral hairy leukoplakia. Lymphoma is an AIDS diagnosis; hairy leukoplakia is not.

HAIRY LEUKOPLAKIA (HL)
Seen in immunocompromised individuals, after organ transplants. and in HIV infection. Most AIDS patients also have been infected by Epstein Barr virus. Hairy leukoplakia is a novel disease unique to HIV-infected individuals. The view that both the Epstein Barr and Papilloma virus cause HL has recently been challenged. Currently EBV is solely implicated. The disease manifests as white lesions on the lateral margins of the tongue. The lesions may be smooth or become so thick that hair-like projections appear. HL is one of the diseases that is highly predictive of developing AIDS.
Treatment
Acyclovir (which treats HSV) sometimes decreases EBV, resulting in decreased HL lesions. Ganciclovir, AZT, topical vitamin A, podophyllin, surgical incision and freezing will suppress the appearance of the lesions.

HERPES SIMPLEX VIRUS I AND II
Herpes usually involves recurrent outbreaks of lesions. In HIV-infected individuals the lesions do not heal as quickly. Ulcers of more than one month's duration, or bronchitis, pneumonitis or esophagitis constitute an AIDS diagnosis. Because HSV retreats along the nerves to the ganglia at the base of the spine, to be reactivated with trauma or immune suppression, there is no cure. The herpes simplex virus (HSV) is usually within the body prior to infection with HIV. When the immune system becomes weakened by HIV, the herpes simplex virus becomes active. HSV appears as tiny fluid-filled blisters and can affect the following: Lips or mouth, Eyes, Genital area, Anal Area, Buttocks, Thighs
Symptoms
Painful fluid-filled blisters and open lesions at involved site
Treatment
Acyclovir (or new similar drugs) or Foscarnet serve to diminish the severity of the lesions, and reduce the time between outbreaks, however. Acyclovir resistant strains have developed within the same individual. Substitution of foscarnet for acyclovir may decrease the resistance to acyclovir.

HISTOPLASMOSIS, DISSEMINATED (fungus) Pneumonia is often seen as well as damage to the liver and bone marrow. Outside the lungs, this constitutes an AIDS diagnosis. This is endemic in South America and the southeastern portion of the U.S.. It is found in the Caribbean islands and in Africa. Infection is acquired by inhalation of spores from the soil especially where bird and bat excretia are present. Many people have this fungus, histoplasma capulatum, in their body, but it rarely causes disease unless the host is immune compromised, especially those with CD4 cell count less than 100. Histoplasmosis is likely to infect: lungs, skin; but can spread to other organs, including: liver, abdominal wall lining, spleen, colon, heart, and adrenal glands.
Symptoms
Fever and weight loss are common along with coughing and diarrhea. Other symptoms include chills, meningitis, blood abnormalities, and enlarged liver, spleen, lymph, and nodes.
Treatment
Itraconazole is more effective than fluconazole or amphotericin B.

HUMAN HERPES VIRUS 6
May result in fever and rash. HHV-6 (originally named "Human B-lymphotropic Virus") is linked to roseola, a common childhood disease that is accompanied by very high fever and a measles-like rash. Like other Herpes viruses, HHV-6 can persist in a latent form within the host. Questions arise as to whether or not HHV-6 can reemerge in an immunocompromised person, such as someone living with HIV disease. HHV-6 may activate HIV replication. May be implicated in Chronic Fatigue Syndrome.

HUMAN PAPILLOMA VIRUS (warts)
Dry, painless warts on or near the genitals and around the anus . May be painful around anus or urethra. May grow if untreated. Removal of warts may still allow for viral DNA to be present in surrounding tissue. (implicated in cervical, penile and anal cancer)

ISOPORIASIS
Must be chronic intestinal for more than one month to qualify as an AIDS diagnosis.

KAPOSI'S SARCOMA see Malignancies

LYMPHOID INTERSTITIAL PNEUMONIA
Only constitutes an AIDS diagnosis in children. It may be related to CMV infection.

LYMPHOMA see Malignancies

MALIGNANCIES
Malignant disease in the setting of HIV infection highlights the role of impaired immunity in the development of various types of cancer.
HIV-associated malignancies include:
Kaposi's sarcoma
Non-Hodgkin's Lymphoma
Primary CNS Lymphoma
Cervical Cancer
Possible HIV association includes:
Anorectal Carcinoma
Hodgkin's Disease

KAPOSI'S SARCOMA (K.S.) (Cancer as an opportunistic infection?)
K.S. was first discovered in 1872 by M. Kaposi. It is a tumor of endothelial or spindle cell origin. The disease is characterized by swollen, purple tumors. They are created in K.S. tumor growth which involves tumor cells tapping into the surrounding blood by sprouting a thick network of blood vessels. The surrounding vessels also leak which baths the tumor in blood.
It is a disease primarily of men. Unlike most solid tumors, Kaposi's sarcoma is not characterized by a primary local growth and eventual metastases. Although the precise origin of Kaposi's sarcoma remains in doubt, cell lines suggest the tumor develops from vascular or lymphatic endothelial cells.

Four forms of K.S. are known:
1. Classic K.S. In Europe and the United States K.S. has been found in older men of Italian and Jewish heritage. In these men it takes an indolent form which takes from 10-15 years to cause death. This is the "classic" form of the disease. In these individuals death often occurs from some other illness.
2. Transplant associated K.S. is also found in immunosuppressed individuals, particularly renal transplant recipients.
3. Endemic. K.S. is endemic in Central Africa where it constitutes 10% of all cancers. It is found primarily in a 13/1 male to female ratio. In elderly men it is of an indolent nature, taking 10-15 years to cause death.
4. Epidemic. Found in HIV infection. There has been a similar occurrence in Africa in young adults (25-40) where it is highly aggressive and kills rapidly within 5-8 years. ( ???AIDS-related???.) It kills children within 2-3 years. This more aggressive form of K.S. may involve the lymph nodes and become systemic, invading the internal organs such as the lungs. This form of K.S. is related to immune suppression. It is the common form seen in AIDS, and may result in death within a matter of weeks. AIDS associated K.S. is found primarily in gay and bisexual men, suggesting that it may be an STD of the gay male population. In women, K.S. is most often found in IVDU and sexual partners of bisexual men. However, there are cases of non-HIV-infected individuals with epidemic K.S. This raised the question of involvement by another infectious organism. A member of the Herpes Virus family has been found to be involved in the development of KS. This virus has been called both KSHV (Kaposi's Sarcoma Herpes Virus) and HHV-8 (Human Herpes Virus-8). Researchers at UCSF have announced that they have isolated HHV-8. There are also questions as to whether Oral/anal contact may enhance transmission of this infectious agent.
Signs and symptoms
Depending on the stage of disability, Kaposi's sarcoma may present differently as follows:
In Early HIV Disease, initial presentation (95% of the time) is on the skin or in the mouth with classic red-purple palpable lesions, which are often asymptomatic. 10% of Kaposi's sarcoma cases present with weight loss and more than two weeks of night sweats or fever
In Late HIV Disease, may present as noted above. Previously asymptomatic clients may develop lymphedema with swelling and pain in the lower extremities, genitals or face. May develop pulmonary Kaposi's sarcoma with cough, bronchospasm, difficulty breathing.

LYMPHOMA (Non-Hodgkin's Lymphoma)
Lymphomas are solid tumors within the lymphoid system. They involve rare tumors that most commonly occur in people with suppressed immune systems. One to 15% of people with HIV infection will develop lymphoma. This percentage is increasing as people live longer with HIV disease. HIV associated lymphomas are very aggressive in nature. The majority of lymphomas are B-cell in origin, occasionally they are of T-cell origin. Lymphoma may be found anywhere in the body. Seventy five percent involve extra pulmonary sites. Brain lymphoma is an important disease entity. In one SF study, median survival for treated and untreated individuals was 4.3 months from diagnosis. NHLs are classified according to pathology and morphology and are divided into three categories: low grade, intermediate grade and high grade. NHL involves the CNS, gastrointestinal tract, bone marrow, and liver. Other sites can be affected.
Symptoms: (include)
seizures hemiparesis (weakness in half the body)
headaches disordered consciousness or cognition
night sweats persistent enlarged lymph nodes
weight loss bony pain or tenderness
perirectal pain GI bleeding
fever incontinence (inability to control urinary and bowel functions).
jaundice
Diagnosis is made by CT scan, although the appearance of the tumors can be confused with toxoplasmosis lesions.
Treatment is by chemotherapy (vinblastine; bleomycin; adriamycin; vincristine; etoposide) followed by radiation therapy. Recently, radioimmunotherapy with anti-B1 (anti CD20) mouse monoclonal antibody was given to B cell lymphoma patients with good results. HTLV-I is implicated in some cases of Non-Hodgkin's Lymphoma. Usually HTLV-I is related to the development of leukemia. HHV-8 has been found in some lymphomas. As discussed earlier, HIV appears to be able to selectively insert itself next to an oncogene which can cause lymphoma

PRIMARY CNS LYMPHOMA
In approximately 25% of persons with NHL, the lymphoma is confined to the central nervous system (CNS).
Signs and symptoms:
Confusion Headache
Lethargy Hemiparesis
Cognitive or focal deficits Palsies
Seizures Aphasia

CERVICAL CANCER
Cervical cancer in young women has increased over the past 20 years. Cervical cancer is correlated with onset of sexual relations before the age of 17 (the average age of first sexual intercourse in the U.S. is 16); multiple partners (21% of high school students in one survey said they had already engaged in sexual intercourse with four or more partners); presence of HPV, HSV and HIV cervical infections; smoking; and being the daughter of a woman who took DES, a powerful synthetic estrogen prescribed for morning sickness. Women at risk for cervical cancer and/or HIV infection should be screened regularly by "pap" smears. Women with HIV infection should have a "pap" smear every six months and colposcopy if cervical abnormalities are present. Colposcopy is a visual examination using a special microscope and bright light (colposcope) which magnifies the cervical cells 40x.
An AIDS diagnosis is based on the cancer being invasive which can be determined on a "Pap" smear. Women infected with HIV have a high incidence of cervical dysplasia, placing them at risk for developing cervical cancer. The progression of dysplasia to invasive cancer in HIV infected women is fairly rapid and less responsive to standard treatment.
Signs and symptoms:
Usually discovered by Pap smears since client is asymptomatic
Abnormal Pap test results, which is five to eight times higher than normal
Blood tinged vaginal discharge; Abdominal, pelvic, back or leg pain

ANAL CANCER.
Anal cancer may occur for the same reasons that cervical cancer is seen in HIV disease. Both men and women who are engaging in anal intercourse should have a Pap Smear of the anus annually

MYCOBACTERIUM AVIUM-INTRACELLULARE COMPLEX (MAC/MAI)
A bacterium, related to the tuberculosis bacillus, that is found in birds. It is very rare except in AIDS. For an AIDS diagnosis it must be disseminated in some part of the body other than the lungs. Reported cases of M. avian complex are increasing. This is due to the increased availability of mycobacterial blood cultures which have made it easier to diagnose. This complex appears late in HIV infection. With increased use of antivirals, prophylaxis and treatment of other OIs, people are living longer. This permits increased likelihood of infection with MAI and expression of disease. There is considerable evidence that MAI infections in HIV disease are not reinfections, but rather primary infections via aerosols, standing water or food sources. Typically, MAC/MAI infection involves many sites throughout the body such as:
Lungs Lymph nodes
GI Tract Bone marrow
Liver Blood
Spleen Intestines
Symptoms
Fever/Night sweats Diarrhea
Nausea/Vomiting Abdominal pain
Fatigue Weight loss
Treatment
Clarithromycin (Blaxin) has been approved to treat MAC in conjunction with one other drug. Rifabutin has been approved for MAC prevention.

MYCOBACTERIUM KANASII
Endemic in California, Texas, Louisiana, Illinois and Florida. Affects lungs and may be disseminated throughout the body. Constitutes an AIDS diagnosis if outside the lungs or disseminated.
Symptoms include coughing, weight loss, fever, dyspnea (difficulty in breathing, sputum production, and night sweats).
Treatment isoniazid, rifampin, ethambutol and streptomycin.

NEUTROPENIA
A decrease in the number of circulating neutrophils, which are referred to as the first line of immune defense. The risk of developing an infection increases as neutropenia persists and the absolute neutrophil count (ANC) decreases.
Causes
Medications (AZT, Ganciclovir, Bactrim, Amphotericin B)
Chronic HIV
Radiation Therapy
Tumor Invasion
Signs and symptoms
Absolute neutrophil count (ANC) < 1,000

PELVIC INFLAMMATORY DISEASE (PID)
Most often caused by chlamydia or gonorrhea. These organisms cause infection of the female reproductive tract including the vagina, endometrium, fallopian tubes and abdominal cavity. The endometrium of HIV-infected women tend to have fewer CD4 cells and more leukocytes than non-infected women. This lower local immunity could lead to increased likelihood of PID occurring. The presence of gonorrhea or chlamydia (as well as trichomonas, or candida) increases the likelihood of HIV transmission. The presence of lesions such as genital wart, syphilis chancre, herpes lesions etc. constitute Genital Ulcer Disease which allows entrance of HIV into the body .

PNEUMOCYSTIS CARINII (PCP) (Fungus)
Pneumocystis carinii pneumonia (PCP) is caused by a tiny parasite which infects most individuals during childhood. The parasite is usually dormant, but causes serious illness in people with weakened immune systems. The organisms invade the alveoli of the lungs, preventing them from expanding and causing irritation to the surrounding alveoli. This is the most common infection in people with AIDS in the U.S. and Europe. PCP is not as common in Africa and South America. Pneumocystis is found in the lungs of about 50% of the U.S. population. An intact immune system usually keeps it under control. In the U.S., PCP is the leading cause of fatal opportunistic infection in AIDS. Individuals are at high risk for PCP infection if CD4 cells are less than 200. However, preventative therapy is highly effective. Even with preventative therapy PCP is one of the most common opportunistic illnesses. Pneumocystis carinii infects the lungs.
Symptoms
Fever, persistent dry (non-productive) cough accompanied by shortness of breath, chest pain, and fatigue particularly upon exertion, difficulty in breathing, weight loss, and night sweats.
Diagnostic procedures
Chest x-ray, sputum induction and culture, gallium scan, bronchoscopy
Prevention
In individuals with a CD4 count of > 200, Trimethoprim-sulfamethoxazole (Bactrim;Septra),. This is the most effective but has side effects. Dapsone, fewer side effects than TMP-SMX, aerosolized pentamadine, or atovaquone which is in clinical trials.
Treatment
Systemic treatment preferred. Pentamadine (IV); trimethoprim-sulfamethoxazole (Septra, Bactrim, co-trimoxazole) most effective.; Dapsone or trimethoprim-dapsone; Trimetrexate (in clinical trials); 566C80 (in clinical trials with limited expanded access). Primaquine with clindamycin (cleosin, Aralen) Atovaquone (Mepron) appears to be as effective as IV pentamidine with fewer adverse side effects, and is equally effective as TMP-SMX (Berlin). Eflornithine. Corticsteroids may be used in conjunction with any of these medications in moderate to severe cases. Pentamadine can impair kidney function or cause a drop in blood sugar; co-trimoxazole can produce severe nausea, skin rashes, fevers, decreased white blood cell count, decreased platelets and liver inflammation.

PERSISTENT GENERALIZED LYMPHADENOPATHY (PGL)
This involves lymph node enlargement of 1 cm or greater at two or more extra inguinal sites persisting for more than three months in the absence of a concurrent illness or condition other than HIV infection to explain the findings). While PGL is not indicative of progression to AIDS, HIV can destroy the integrity of the lymph node. PGL may decrease prior to an AIDS diagnosis, which may be indicative of immune system failure. In AIDS the lymph nodes regress and may be difficult to detect clinically. On autopsy they have atrophied.

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
PML is a progressive central nervous system disease caused by the papovavirus. (JC virus). JC stands for the initials of the patient from whose brain the virus was obtained). JC virus destroys the myelin sheath which is involved in nerve message transfer. Multiple lesions develop in white matter of the cerebrum, and sometimes in the brain stem or cerebellum, resulting in focal neurologic deficits. PML is most often seen in people with certain cancerous conditions of the blood, or conditions in which cell-mediated immunity is impaired. It is found throughout the U.S. The onset of PML is gradual in people with HIV infection. The disease progresses rapidly, often leads to dementia, blindness and paralysis. In most cases, death results within one year.
Signs and Symptoms
Focal neurological signs are common, including impairment of vision and speech, mental deterioration, sensory abnormalities and ataxia (unsteady, wide-based gait). The patient rarely has headaches and fever.
Diagnosis
Diagnosis is made on clinical symptoms and CT scan.
Treatment
Brain biopsy is not done because of the invasiveness of the procedure and the fact that no treatment is available. Death usually occurs within one year.

PSEUDOMONAS (Bacteremia)
Treatment
ceftazidime and ciprofloxacin

RECURRENT PNEUMONIA (more than one episode within a year)

SALMONELLA SEPTICEMIA RECURRENT
Non-typhoid Salmonella: Primary bacteremia (bacteria in the blood), meningitis.
Treatment
ampicillin, gentamicin; ceftazidine, chloramphenicol, trimethoprim-sulfamethoxazole

STRONGYLOIDES STERCOLIS (parasitic round worm)
Not usually found in humans. In HIV disease, it is found in the intestines and lungs. Outside the intestines it constitutes an AIDS diagnosis. Geographically it is found most often in subtropical regions. In the U.S., it is found in the rural south.
Treatment
thiabendazole

SYPHILIS
Caused by the spirochete Treponema pallidum.
Four stages:
1. Primary stage: appearance of a single painless sore (chancre) 10-90 days after contact, at site of contact (where spirochete entered the body), e.g. on the penis, cervix, vagina, mouth, anus, lips, finger, breast. This heals within 2-6 weeks. This is a highly contagious stage.
2. Secondary stage: begins anywhere from 1-6 weeks after the chancre heals (if no treatment is given). Characterized by pale red or pinkish rash (often on palms and soles of feet), sore throat, fever, headache, swollen glands, pain in joints, hair loss, poor appetite, weight loss. Moist sores (condyloma lata) may appear on genitals and anus and are highly infectious. In 60% of individuals the symptoms are mild and may be overlooked. This stage lasts three to six months and can come and go periodically. This stage is contagious.
3. Latent stage: No symptoms. In 1/3 of people the disease will not progress further. Not contagious except to fetus. The spirochete, however, burrows its way into deeper tissue.
4. Tertiary stage: The spirochete has invaded all tissue of the body. It can cause tumor-like sores (gummas), heart disease, paralysis, psychosis, eye problems, and death. Not contagious during this stage except to fetus.

Congenital syphilis: The spirochete can cross the placenta and infect the fetus at any stage. This is why tests for syphilis are done on all pregnant women, (a woman may be unaware that she has the disease). Fetus can develop bone and teeth deformities, kidney problems, etc. Treat before 16th week of pregnancy.

Diagnosis
VDRL, FTA-ABS tests most common RPR. Examine blood for antibodies.
Occasionally there are false positive results.
Physical exam, including pelvic to look for chancre on cervix or vagina.
Treatment
Penicillin, doxycycline, tetracycline, erythromycin. An acute fever may occur after treatment. In pregnant women early labor may occur.

Syphilis, which has also been called "the great imitator," may also be found in a latent form. One-third of those with syphilis do not progress to the tertiary stage, the stage in which neurosyphilis is seen. The assumption is that the immune system has dealt effectively with the infection, perhaps controlling it so there is no further disease progression unless the immune system is compromised.. Like TB, antibody tests are not effective methods of diagnosis in people with AIDS. After a twenty year decline in the number of syphilis cases in the U.S., 1986 saw a sharp increase syphilis cases. There is a connection with AIDS that is quite similar to the connection previously discussed concerning TB.

TOXOPLASMOSIS GONDII (Toxo) (Protozoa)
An intracellular parasite found in about 40-50% of Americans. Once acquired it is a lifelong infection. An intact immune system keeps it under control. It infects the brain, heart or lungs. In the brain it qualifies as an AIDS diagnosis. This parasite is in the feces of cats, rodents, birds and carnivores. Ingestion of the oocysts usually found in undercooked meat (beef, lamb or pork), or ingestion of the sporocysts which are commonly found in feces (oral-fecal route) can cause infection in immunocompromised humans. With immune system depression, previously acquired infections grow to clinical disease. Those with past exposures have about a 30% chance of developing brain toxoplasmosis. About 50% of brain damage in AIDS is due to toxoplasmosis.

Signs and Symptoms
Clinical manifestations include malaise, fever, headaches, and seizures. The most common presentation includes some focal neurologic symptom, such as specific muscle weakness, or the presence of abnormal findings on a neurological exam. Mental status changes, including confusion and disorientation are also common.
Diagnosis
Infection tends to occur when the CD4 cell count is less than 100. Approximately 5-45% of the United States population has been infected, depending on geographic location. Toxoplasmosis commonly affects the brain and signs and symptoms occur gradually and progressively. Diagnosis is most often made by CT (computerized tomography) or MRI (magnetic resonance imaging scan, a better technique than the CAT scan). Other scans include SPECT (a nuclear scanner costing $300,000 dollars) and the PET scanner which costs $3 million. These show characteristic lesions throughout the brain. Brain biopsy can also be done, but this is a very invasive procedure. Another method is to initiate treatment and monitor improvement. About three-fourths of those infected will respond to treatment.
Treatment
Prophylaxis: the oral agents used in the prevention and treatment of PCP also protect against toxoplasmosis. (Septra, Bactrim, dapsone, atovaquone) Treatment will need to be lifelong. Reports in early October 1993 indicate that Pyrimethamine (anti-malarial) and clindamycin (antibiotic) in combination appear to be very effective in combating brain toxoplasmosis.

TUBERCULOSIS (Mycobacterium Tuberculosis)
Most often found in the lungs, and can be disseminated throughout the body (extrapulmonary). It is found in the lungs of 74-100% of people with TB and HIV. Seventy percent of patients with TB and HIV disease show extrapulmonary TB. Extra pulmonary sites include: lymph nodes, blood, and central nervous system (TB meningitis is becoming more common).

In the majority of cases, the OIs associated with HIV infection are not a problem to those whose immune systems are intact. An exception to this is tuberculosis. Between 1953 and 1984 there was a steady decline in reported TB (6% decline per year) in the U.S. There has been a sharp increase in the number of cases of tuberculosis in the past few years. It is estimated that, currently, 10-15 million Americans are infected by TB. Beginning in the 1960s outpatient settings supplanted specialized hospitals, and funding for research was reduced. Immigration from areas where TB was endemic increased in the 1980s. Another factor is related to coexisting HIV infection which increases the risk of TB infection. DNA Studies from San Francisco and New York show that 33% of the TB cases are new infections not recurrences. From 1984 to 1986, in New York, the reported TB cases increased 36% (from 1,630 cases to 2,223 cases). This compares to a 2% increase nation-wide (from 22,255 to 22,768). The increase in NY cases was concentrated in 80% of all NYC AIDS patients. Since 1985 there has been a 16% increase in the reported annual cases of TB. It is estimated that there are more than ten million TB-infected people in the U.S., compared to one million infected with HIV.

There are two possible mechanisms by which the immunodeficiency caused by HIV infection may increase the risk of TB. HIV-related immunodeficiency could increase susceptibility to new infection and permit the infection to progress rapidly to clinically apparent disease, and/or it may allow a previously latent tuberculosis infection to progress to clinically apparent disease. There is a clustering of TB diagnoses around the time of AIDS diagnosis in studies of patients with HIV infection. This suggests that TB in patients with AIDS often results from reactivation of a previously acquired latent infection. The present risk of new TB infections in the U.S. is too low to account for the high incidence of TB among AIDS patients. There is also a high correlation between IV drug use and TB/AIDS. 57% of TB/AIDS patients in one study were IV drug users. It is recommended that IV drug users be tested for, and if positive, be treated for TB. The most common test is a DTH skin test. If delayed type hypersensitivity reactions are affected by immune suppression (anergy), the diagnosis may be difficult. X-rays may not allow for a definitive diagnosis, and cultures require a minimum of two to four weeks for primary isolation. This failure to diagnose TB rapidly results in higher mortality rates as well as transmission to other individuals. Incidence of TB in the homeless continues to rise. There is also an increase in hospital (nosocomial) infections. Cough-inducing procedures such as sputum induction, aerosolized pentamadine and brochoscopy require strict isolation or infection control procedures which are not always carried out. HIV infection may also interfere with the effectiveness of anti-tuberculosis chemotherapy.

There has also been an increase in drug resistant cases of TB. In a recent CDC survey, only 61% of all cultures for TB were tested for drug susceptibility. This can result in patients being treated with ineffective drugs, and thus continuing to transmit infection. Also, drug use, dementia, etc. may result in noncompliance in taking medications. Transmission of the drug resistant strains of TB is of tremendous concern. Ninety percent of the cases of drug resistant TB have occurred in HIV-infected people. There have been at least 6 outbreaks of multiple drug-resistant TB in the two years from 1990-1992. Some strains are resistant to the best and most common anti-tuberculosis drugs (isoniazid and rifampin.) Others are resistant to as many as seven of the current drugs. There is also concern about some drugs not currently available (streptomycin & para aminosalicylic), and others such as isoniazid, cyclosterine, and ethionamide are not consistently available in the U.S. The CDC has recently formed a federal Tuberculosis Task Force to promote collaboration among the Federal agencies, like the CDC, National Institutes of Health (NIH), and the Food and Drug Administration (FDA). Federal funding for TB research, prevention and treatment has not increased significantly. In fact the U.S. Public Health hospital in San Francisco was closed a few years ago. State funding for medical problems in general is affected by the current recession as well. In California in 1990, the cost of treating ten cases of drug-resistant TB was $950,000.
Treatment
1. 81-86% effective; four drug regimen: Isoniazid, rifampin, ethambutol and pyrazinamide; recommended by Mount Sinai school of medicine.
2. 86-89% effective; five drug regimen that adds ethionamide.
3. 91-100% effective; six drug regimen adds either ciprofloaxin, cycloserine, capreomycin or ethinamide.
4. >95% effective; seven drug regimen includes 3 of the previous additions. This regimen is the only one effective against multi-drug-resistant active TB.

VARICELLA ZOSTER VIRUS
Causes retinitis, encephalitis, shingles. Shingles is reemergence of chicken pox along the localized dermatomes of the body (such as the shoulder, around the waist, etc.) Dermatomes are areas of skin that are innervated by various spinal cord segments. Shingles is extremely painful.

WASTING SYNDROME see Constitutional Disease

CLINICAL MANIFESTATIONS IN WOMEN
Women with HIV disease may have lower genital tract infections. Genital warts (HPV), genital herpes, candidiasis, and pelvic inflammatory disease (PID) (infection in the uterus, fallopian tubes and perhaps into the abdominal cavity) are of particular concern. These infections tend to be more aggressive and recurring. There is an increase in the number of CD8+ lymphocytes but a decrease in their cytolytic ability. They may lack the ability to respond to viral infection. This may explain why HIV+ women are more susceptible to viral and fungal infections.
Urinary tract infections also are common. Only 3% of women have K.S. It usually develops when the women are more immune deficient. Women with K.S. have a shorter survival time than men. Lymphoma is much more common in women. Neoplasia of the genital tract is a serious problem for women. Thirty-five to eighty percent of HIV positive women have cervical intraepithelial neoplasia (CIN). Reports indicate an increase in CIN, more severe dysplasia and rapidly progressing invasive cervical cancer lesions, and death from cervical neoplasms with increasing immune suppression. There is a decrease in the proportion of immunocompetent cells in the cervix.
Cancers of the vulva and perianal region are also common. Women have a lower incidence of PCP as the AIDS defining illness. Esophageal candidiasis and wasting syndrome are common. Recurrent and severe vaginal candidiasis is common but does not qualify as an AIDS defining disease. It is unclear what effect HIV infection has on an individual pregnancy. Loss of endocrine function has not been studied as it has in men. Thrombocytopenia is less apt to occur in women than men, while anemia is more apt to occur in women. Women with clotting disorders tend to bleed excessively during menstrual periods. There is also a high fetal loss in HIV+ women who are pregnant

CLINICAL MANIFESTATIONS IN CHILDREN
HIV-infected infants show failure to thrive as well as failure to achieve the developmental milestones. Language ability is delayed. The clinical manifestations in children are somewhat different from those in adults. They are more apt to have severe bacterial infections and lymphoid interstitial pneumonia and candida esophagitis. Encephalopathy and wasting syndrome are common, as are recurrent viral infections, such as HSV infections. Unexplained cardiac abnormalities are seen, and those children with impaired neural development seem more likely to suffer life-threatening heart attacks. Hyperdynamic left ventricular function (HLVF in which the heart beats too powerfully) occurs in one half of HIV-infected children. This appears to be related to abnormalities in the autonomic nervous system.


REFERENCE E. Drug Side Effects ;-- by Sharon Ochoa and Elisa Hernandez

Table 1.6 Treatment regimens for HIV Disease

SYSTEM/Problem DRUG COMMON SIDE EFFECTS
GENERAL

Anti-retroviral Zidovudine (AZT, Retrovir) Headache, anorexia, nausea, bone marrow suppression, malaise, hypertension

Didanosine (DDI, Videx) Pancreatitis, peripheral neuropathy, nausea, diarrhea, increase frequency of oral ulcerations

Zalcitabine (ddC, HIVID) Pancreatitis, peripheral neuropathy, mouth ulcers, congestive heart failure

Veramune (Nevirapine) Rash most common, incidence of a lethal inflammation of the skin or mucous membrane was less common

Lamivudine(3TC) Well tolerated with few side effects, Nausea and vomiting reported in 15 - 26% of clinical trials. Headaches in 9%, when used with AZT. At higher doses (3TC caused deficiencies in white blood cells specifically neutrophils, which can cause increased risk of infection

Non-nucleoside Antiviral Inhibitors Delevirdine
Nevirapine
Atevirdine
Loviride Experimental Antiviral compounds although they are structurally different they work in a similar manner. Greater focus on these compounds comes from the observation that they can inhibit reverse transcription without the exhibiting the non-specific toxicities o f the nucleoside analogs like AZT.

Stavudine (d4T) Peripheral neuropathy, anemia

Weight Loss Megesterol (Megace) Nausea, vomiting, edema, depression , diarrhea, impotence, increased blood pressure, insomnia, nausea

Dronabinol (Marinol) CNS problems, elation, easy laughing, dizziness, confusion, drowsiness
(MAC) Clarithromycin (Biaxin) Nausea, vomiting, abdominal pain rash, abnormal, taste

Ethambutol (Myambutol) decrease in visual acuity,, rashes, joint pain, changes in appetite, nausea, vomiting, upset stomach, abdominal pain, fever, malaise, headache , dizziness, confusion

Clofazimine (Lamprene) Purple-reddish skin discoloration, GI distress, dizziness, diarrhea, nausea, vomiting

Ciprofloxacin (Cipro) Most frequently reported effects headache, nausea, restlessness, rash,. Less frequently reported are convulsions, and pressure in the brain by some people

Rifampin (Rifadin) Flu-like symptoms, heart burn, upset stomach, loss of appetite, nausea, vomiting, gas, cramps, diarrhea, drowsiness, headache, menstrual irregularities, dizziness, fever, pain in the extremities, blurred vision, and allergic reactions

Rifabutin (Mycobutin) Discoloration of urine and sweat, stomach upset and rashes

Amikacin Ototoxicity, kidney toxicity, less frequent vertigo. Sustained use: hearing loss, loss of balance, rarely acute muscle paralysis.

(MAC/TB) Mycobacterium Isoniazid (INH) Most common effect, peripheral neuropathy, skin rash, tuberculosis (TB) fever, liver dysfunction. Severe fatal non-infectious hepatitis in some people

Rifampin flu-like symptoms, heart burn, upset stomach, loss of appetite, nausea, vomiting, gas, cramps, diarrhea, drowsiness, headache, menstrual irregularities, dizziness, fever, pain in the extremities, blurred vision, and allergic reaction

Pyrazinamide (PZA) Vomiting, joint pain, liver damage, reduced Blood cell and platelet count

Ethambutol flu-like symptoms, heart burn, upset stomach, loss of appetite, nausea, vomiting, gas, cramps, diarrhea, drowsiness, headache, menstrual irregularities, dizziness, fever, pain in the extremities, blurred vision, and allergic reaction

Histoplasmosis Amphotericin B Fevers, chills, headache, nausea, vomiting, diarrhea, bone marrow suppression, abnormal renal function, phlebitis , kidney toxicity, anemia

Itraconazole (Sporanox) Diarrhea, headache, stomach pain, loss of appetite, rashes, swelling, increased blood pressure, fatigue

SKIN/MUCO-CUTANEOUS

Kaposi's sarcoma Local radiation treatment Skin redness or oral lesions in head and neck regions
Systemic chemotherapy Varies according to chemotherapy agent administered
Alpha-Interferon Most common to CNS is dizziness, flu-like symptoms, muscle weakness, headache, chills, fatigue, myalgia, decreased platelets, decreased white blood cells, bone pain, loss of appetite, nausea, diarrhea

Herpes simplex Acyclovir (Zovirax) Nausea, vomiting, diarrhea, dizziness, headache

Foscarnet Headache, appetite loss, nausea, electrolyte imbalance which may lead to seizures, anemia,, fatigue, fever, muscle weakness to a lesser degree.



OPHTHALMOLOGIC

Cytomegalovirus Ganciclovir (Cytovene) Most frequent; reduction of number of neutrophils and platelets , kidney damage. Less frequent; bone marrow suppression, nausea, diarrhea, muscle aches, headache, phlebitis rash

Foscarnet Headache, appetite loss, nausea, electrolyte imbalance which may lead to seizures, anemia,, fatigue, fever, muscle weakness to a lesser degree.
ORAL CAVITY

Candida Ketoconazole (Nizoral) Primary effects; vomiting, nausea, abdominal pain, itching, insomnia, rarely, liver toxicity, rash,

Fluconazole (Diflucan) Nausea, abdominal pain, headache
skin rash, diarrhea

Clotrimazole (Mycelex) Very few have nausea and vomiting,
Most common effects involve skin irritations, redness and peeling

Mystatin (Mycostatin) Rarely causes side effects,. Occasionally,;diarrhea, nausea, vomiting

Amphotericin-B Fevers, chills, headache, nausea, vomiting, diarrhea, bone marrow suppression, abnormal renal function, phlebitis , kidney toxicity, anemia

GASTROINTESTINAL

Nausea/Diarrhea Compazine Drowsiness, dizziness, CNS reactions, blurred vision, skin reactions . Tardive dyskinesia - involuntary muscle movements which involve the tongue, face, mouth lips , jaw, torso and extremities. In some people neuroleptic syndrome.

Reglan Drowsiness, dizziness, CNS reactions, blurred vision, skin reactions . Tardive dyskinesia - involuntary muscle movements which involve the tongue, face, mouth lips , jaw, torso and extremities. In some people neuroleptic syndrome.

Ativan Sedation, dizziness, unsteadiness, antegrade amnesia

Imodium Abdominal cramps, nausea, dizziness, drowsiness, vomiting , constipation, dry mouth

Lomotil Nausea, vomiting, abdominal discomfort, numbness, euphoria, depression

Octreotide (Sandostatin) Nausea, pain at injection site

Paregoric Altered mental status, side effects similar to narcotic analgesics, cold symptoms, bruising, swelling, flushing, blurred vision and hair loss

Cyptosporidium Humatin Few people report nausea, vomiting, epigastric pain, diarrhea, abdominal cramps. Rarely reported kidney toxicity and hearing loss

PULMONARY

PCP Dapsone Most serious, anemia's with shortened red blood cell life span, rise in abnormal hemoglobin, Peripheral neuropathy. Less common; nausea, vomiting, bone marrow, suppression

(PCP) Pentamidine (aerosolized) Minimal side effects in inhalant form; cough and bronchospasm, decreased appetite, dizziness, rashes, nausea, congestion, and night sweats

Mepron Rash, drug fever, headache, nausea, diarrhea,

CENTRAL NERVOUS SYSTEM

Toxoplasmosis Clindamycin Nausea, vomiting, diarrhea, rash, liver toxicity, severe colitis, allergic reactions , jaundice

Leucovorin (folinic acid) Relatively well tolerated, some people may become allergic to it

Pyrimethamine Nausea, vomiting, bone marrow suppression, reduced red blood cell and platelet count. Allergic reactions when used with sulfa drugs.

Sulfadiazine Fever, chills, rash, decreased platelets, decreased white blood cells, allergic reactions, anaphylactic shock, light sensitivity

Trimethoprim-sulfa (Bactrim, Septra) Nausea, vomiting, fever, chills, loss of appetite , rash, decreased platelets and white blood cell count, vomiting and bone marrow suppression rash, decreased platelets, decreased white blood cells

Cryptococcal meningitis Amphotericin-B Fevers, chills, headache, nausea, vomiting, diarrhea, bone marrow suppression, abnormal renal function, phlebitis , kidney toxicity, anemia

Fluconazole (Diflucan) Nausea, abdominal pain, headache, skin rash, diarrhea

Treatment of mental depression Amitriptyline (Elavil) Drowsiness, sleepiness, disorientation, confusion, hallucinations, seizures, orthostatic hypotension

Peripheral neuropathy Mexiletine (Mexitil) Nausea, vomiting, dizziness, tremors, rapid heart beat, chest pains, loss of coordination


REFERENCE F. Clinical Manifestations by Organ System

Infection with HIV leads to a complex multisystem disease. Opportunistic infections and malignancies, resulting from progressive immunological impairment, may involve any organ system. The following HIV-related disorders are listed by organ system to provide a better understanding of the physical impact that occurs with various conditions.

Clinical Manifestations: A systems approach
Deborah Royal R.N., A.N.P., M.S.N.


Blood Disorders
Anemia (low red blood cells)
Blood clotting problems
Lymphoma
Neutropenia (low white blood cells

Cardiovascular Disorders
Endocarditis (heart infection)
Myocardial (heart muscle) disease

Constitutional Syndrome:
Fever
Wasting

Dermatalogic Problems
Bacillary angiomatosis
Candida
Dermatophyte
Folliculitis (fungal, bacterial, scabies)
Herpes simplex virus I and II
Human papilloma virus (warts)
Kaposi's Sarcoma (KS)
Molluscum contagiosum (virus)
Psoriasis
Seborrheic dermatitis
Varicella zoster (virus ) (shingles)
Xeraderma (dry skin)

Endocrine
Adrenal insufficiency
Decrease testosterone levels in men

Female Gynecological
Candida
Cervical dysplasia/cancer
Herpes
HIV
HPV
PID
Syphilis
Urinary tract infections
Gastrointestinal Tract
Oral
Bacterial gingivitis
Candida
Esophagitis
Hairy leukoplakia
Herpes
KS
Xerostomia
Upper GI
Candida
CMV
Herpes
Idiopathic ulcers
KS
Abdomen
Amoebic liver abscess
CMV
Constipation/obstruction
Cryptosporidium
Hepatitis
KS
Lymphoma
MAC/MAI
Reflux
Ulcer disease
Colon:
Bacterial:
Campylobacter
Infectious diarrhea
MAC
Salmonella
Shigella
Parasitic
Cryptosporidium
Cyclospora
Entamoeba histolytica
Giardia
Isopora
Microsporidia
Viral -- CMV
Hematologic Manifestations
Anemia
Neutropenia
Thrombocytopenia

Liver
Biliary obstruction
ETOH
Hepatitis
HIV-related gallbladder disease
HIV-related liver disease
Infiltrative liver disease

Male Genito/Urinary
Candida
Herpes
HPV
Orchitis
Proctitis
Syphilis

Malignancies
Anal cancer
Cervical cancer
KS
Non-hodgkin's lymphoma
Musculoskelatal Diseases
Arthralgia
Arthritis
Muscle wasting and weakness
Myopathy
Psoriatic arthritis
Reiter's syndrome

Neurological Syndrome
AIDS Dementia Complex (ADC or HADC --Human ADC)
aseptic (caused by cytokines)
bacterial
Depression; anxiety
Encephalitis
Hearing loss
Lymphoma
Meningitis (inflammation of meninges)
Peripheral Nervous System Syndrome
Progressive Multifocal Leukoencephalopathy (PML)
Progressive polyradiculotherapy (etiology unknown)
Sensory neuropathy (etiology unknown)
Syphillis
TB
Toxoplasmosis

Pulmonary Syndromes (lungs)
Bacterial pneumonia
Blastomycosis (fungal)
Coccidiomycosis (Valley fever)
Cryptococcus neoformans (fungus)
Cytomegalovirus (CMV)
Histoplasmosis
Kaposi's sarcoma
Lymphoid interstitial pheumonia (AIDS diagnosis in children)
M. avium complex (MAC) (mycobacterium)
M. Tuberculosis
Pneumocysits carinii Pneumonia (PCP) (fungus--has been known as a protozoan)
Pulmonary K.S.

Rectal
Chlamydia
CMV
Gonorrhea
Herpes
HIV
HPV
Syphilis

Renal Disorders
HIV-associated kidney disease

Retinal Syndromes
AIDS-associated retinopathy
Candida
Cryptococcus
Cytomegalovirus (CMV) retinitis
Herpes
Pneumocystis
Toxoplasmosis



REFERENCE G. Monitoring The HIV-Infected Individual
On the average, HIV infected individuals develop AIDS between 10-12 years after infection. However, it is important to remember that 13% of HIV infected individuals have remained healthy for over 17 years! While it is not possible to predict who will develop AIDS and how quickly they will develop it, scientists are trying to compile as much information as possible on various serological events to see if this type of information can be used to predict with some degree of accuracy the likelihood of progression into symptoms of AIDS (surrogate markers). The CD4 T cells counts, although widely used clinically, are only a crude predictor of progression. There are many people with low CD4 counts who are healthy, and many with high CD4 counts who have shown disease progression.

Following HIV infection a sequence of serological events occur that can be used to diagnose HIV infection and to predict disease progression, culminating in an AIDS diagnosis. Following infection the virus appears to replicate actively and the viral core protein p24 can be detected in blood serum. The p24 antigen is detectable in the serum for only a few weeks following infection and then disappears as the antibody response (seroconversion) develops. In most cases the time between infection and seroconversion is 6 weeks, but in some individuals the lag period has lasted for more than 4 years.

At seroconversion antibody to HIV antigens can be detected. This antibody is specific for many of the viral structural proteins including gp160, gp120, gp41, p24 and p17. The appearance of antibody to the p24 core protein has been particularly useful as its presence correlates with at least a somewhat effective immune system response, with up to 10 billion viral particles being produced and destroyed daily. When the antibody to p24 begins to decline, there is a corresponding increase in the appearance of p24 antigen in the serum which is indicative of increased viral replication and viral load. The number of copies of RNA/ml increase as viral replication increases (viral load). Despite the production of up to 2 billion CD4+ cells daily this is associated with a decline in the CD4 count and percentage. These three changes are associated with disease progression. The decline in CD4 count or percentage, plus increase in p24 antigen have been used to predict progression to AIDS more reliably. In HIV-infected individuals with CD4+ T cell counts above 400, about 45% will progress to AIDS within 3 years if they are also positive for p24 antigen. If the CD4+ T cell count is below 400 and the individual is also positive for p24, then the likelihood is 80% that the individual will progress to AIDS within 3 years.

More recently, high plasma levels of HIV RNA (viral load) have been shown to be a strong predictor of rapid disease progression. This is independent of the CD4 count. In 42 gay men followed between 3 to 11 years, CD4 counts, HIV-RNA level and p24 increase all predicted disease progression. In addition these, serum levels of several other cellular products of activated lymphocytes have also been shown to serve as prognostic indicators of progression to AIDS. Among these immune activation markers are: b2-microglobulin, neopterin, soluble CD8, and soluble IL-2 receptor. b2-microglobulin is released with destructionof HIV-infected cells. Neopterin is a metabolite produced by active macrophages Soluble CD8 and soluble IL-2 receptor are both T cell membrane molecules that are released from activated T cells.


REFERENCE H. Risk Reduction
AIDS will require a worldwide effort to stop it. There are many difficulties to overcome in the development of a vaccine to prevent HIV, and it will take a long time to do so. Whether the numbers of infected individuals and AIDS cases grow depends on efforts to educate people on how to avoid contracting the virus.

Risk Of HIV Transmission Via Sexual Behavior
Safe Behaviors: No sharing of blood, semen, or vaginal secretions
Fantasy/talking about sex
Dry kissing (social)
Body massage, hugging, fondling
Body to body rubbing (no open sores)
Kissing or licking the body: clean skin, no open sores, no contact of mouth with genitals
Light S & M activities (no bruising or bleeding)
Masturbation (with or without one's own sex toys) alone or in the presence of another person
Mutual genital pleasuring using latex gloves, finger cots or latex condom over fingers
Showering, bathing, hot tubbing
Manual or oral stimulation of female breasts (no breaks in the skin or milk production)
Abstinence


Probably safe;: Probably no sharing of blood, semen, or vaginal fluids
French kissing with no cuts, sores, or bleeding gums in either person's mouth
Fellatio with condom
Cunnilingus with latex or plastic wrap between vulva and tongue
Manual stimulation of male and/or female genitalia with no protection and no breaks in the skin (cuts, rashes sores, irritation)
Oral-anal contact using latex between tongue and anus


Risky behaviors;: involve likelihood of sharing blood, semen, or vaginal fluids
Unprotected fellatio
Unprotected cunnilingus
Unprotected manual stimulation of prostate, anus or vagina by partner (fisting =fingers in vagina or anus, if more than fingers inserted, this is a high risk behavior)
Oral manipulation of breasts if milk is being produced, or if there are breaks in the skin
Any activity that allows blood, semen or vaginal fluid contact with other mucous membrane (the mouth, throat, eyes), or with broken skin


Highest Risk behaviors;: involve sharing of blood, semen. or vaginal fluids
Receptive anal intercourse without a condom (highest risk)
Insertive anal intercourse without a condom
Receptive vaginal intercourse without a condom
Insertive vaginal intercourse without a condom
Sharing objects put in the vagina or anus
Cunnilingus during menstruation
Unprotected oral-anal contact (transmission of pathogenic organisms)

Risk May Be Reduced By;:
Use of latex condom in anal intercourse. Risk further reduced with use of nonoxynol-9
Use of latex condom in vaginal intercourse. Risk further reduced with use of nonoxynol-9
Use of condom on the penis during fellatio
Use of latex or plastic wrap between mouth and female genitalia during cunnilingus
Use of latex gloves, finger cots or condom over fingers for vaginal or anal fisting

Contributing factors
How vigorous is the activity/ Biting-nibbling during oral sex/ Is blood present?
Are condoms used correctly and every time/Check for allergy to nonoxynol-9 (use 6% N9 or less)
Other considerations
Body fluids such as saliva, sweat, tears, sputum, nasal secretions, urine, feces, have not been shown to transmit HIV. They are not considered risky unless they blood visible.

HIV/AIDS is not spread by casual contact. You have to work at it.
HIV/AIDS is not the only sexually transmitted disease that can be prevented.

Safer Sex Guidelines For Lesbian Women
The San Francisco Public Health Department (1993) study showed that lesbian women were three times more likely to be HIV-infected than non-lesbian women.

Lesbians At The Highest Risk for HIV Disease/AIDS
1. Lesbians who share needles or any other paraphernalia (spoons, works, syringes) when using Injecting drugs. This is the single most important risk factor for lesbians. 95% of cases of AIDS in lesbians are from sharing drug needles.

2. Lesbians who have had sexual contact with:
*men who have engaged in same sex sexual behavior
*people of either sex whose sexual histories are unknown
*people who use injecting drugs
*people who are hemophiliac, or who have received blood transfusions between 1979-1985

3. Lesbians who have received blood transfusions or blood products between 1979 and 1985

Lesbians At Lowest Risk for HIV disease/AIDS
1. Lesbians who have been in a mutually monogamous relationship since 1979
2. Lesbians who have been celibate and have received no blood transfusions or blood products since 1979
3. Lesbians whose sexual partners have not been at risk since 1979

Until there is more concrete evidence about women, AIDS and transmission, AIDS experts are advising lesbians to follow safe sex guidelines.

Safe Sex Lesbian Practices: massage, tribadism , frottage, social kissing, voyeurism, masturbation, sex toys that are not shared or are cleaned and dried thoroughly between each partner's use, S & M activities that do not involve blood, vaginal fluids or breast milk, and virtually any other contact that does not involve sharing or contact with blood, vaginal fluids or breast milk.
Possibly Safe Sex Lesbian Practices: cunnilingus with a latex barrier (such as dental dams (a thin square of latex ), genital or anal contact with hands or fingers while wearing surgical latex gloves, finger cots or a condom over the fingers, genital or anal contact with hands or fingers when neither partner has cuts, scratches, or sores on their hands or genitals; French kissing, and external water sports.
Unsafe Sex Lesbian Practices: unprotected cunnilingus (especially during menstruation, because menstrual blood is considered to be the same as any other type of blood) any type blood exchange, oral/anal contact, unprotected hand/vagina or hand/anal contact, urine or feces in the mouth or vagina, and sharing sex toys that come in contact with blood, vaginal fluids or breast milk.

GUIDELINES FOR SAFER ORAL SEX(California Department of Public Health)
1. Avoid alcohol or drug use before and during oral sex
2. Cover your partner's penis, vagina, or anus with a protective barrier before any mouth contact.
3. Use only water-based lubricants
4. Avoid oral sex when sexually transmitted diseases or other medical conditions affecting the genitals, mouth and/or throat are present or suspected (such as when experiencing any pain, irritation, bleeding, blisters, lesions, sores, or discharge.
5. Avoid rough or vigorous oral sex and check for breaks or cuts in the skin periodically.
6. Be cautious with sharp objects
7. Take a moment before and after oral sex to wash the penis, vagina or anal area with mild soap, and towel dry.
8. Don't brush or floss your teeth before or after oral sex.

METHODS FOR REDUCING THE RISK OF CONTRACTING STDS:
Be informed
Be observant
Be selective
Be honest
Be cautious
Communicate with partner about risk reduction behavior BEFORE beginning sexual behavior.
Set limits before you begin.
Limit the use of alcohol and other drugs, especially before and during sex. You may find that these substances act as disinhibitors, and you may not follow through with the limits you set.
Keep condoms, spermicides and toys ready and within easy reach. You are more apt to use them if they are handy.
Use latex gloves for activities that may expose you to blood, semen or vaginal fluids, if there are breaks in the skin on your hands.
Make sure that you are not allergic to nonoxynol-9 products before using them. An allergic reaction can cause irritation or breaks in the mucous membrane that enhance the likelihood of infection occurring. Use of products that contain a high percentage of nonoxynol-9 can also destroy the normal vaginal bacteria which can also increase the likelihood of vaginitis.
Be tested and treated promptly (partner also) for disease that have treatments, remembering that there is no cure for either HIV or other viral infections. When treatments are given for STDs, make sure you abstain from sexual contact until the treatment is completed.
Be honest with your partner

Try to develop a healthy attitude about sex, be clear about your sexual values, so that you feel free to make clear decisions about your sexual behavior so that you don't have any "accidents".

Sex isn't dirty but it does require a sense of responsibility


REFERENCE I. Glossary

Abbreviations
APC: Antigen Presenting Cell
ARC: AIDS related complex
ARV: AIDS Related virus: Name given by Jay Levy before the HIV name was standardized.
CAF: Cellular antiviral factor
CD4: A molecule found on T cells, dendritic cells, macrophages etc. (TH cells express the highest level of CD4 molecules )
CDC: Center for Disease Control and Prevention
CTLs: Cytotoxic T-lymphocytes
DTH: Delayed type hypersensitivity
Dx: Diagnosis
EPO: Erythropoietin
GRID: Gay Related Immune Deficiency
HIV-2: A strain of HIV that is believed to be less pathogenic than HIV-1. Mainly found in West Africa. Has a lower binding affinity for CD4 cells which may account for lower pathogenicity compared to HIV 1.
HTLV III: Human T cell Lymphotropic Virus III. Name given by Robert Gallo before the HIV name was standardized.
KS: Kaposi’s sarcoma
LAV: Lymphadenopathy virus. Name given by Luc Montagnier’s group before the HIV name was standardized.
MHC: Major histocompatibility complex
Mx: Maintenance
PCP: Pneumocystis carinii pneumonia
PCR: Polymerase chain reaction
PGL: Persistent generalized lymphadenopathy
PLWA: Person/People living with AIDS
PML: Progressive multifocal leukoencephalopathy
Px: Prophylaxis; prevention
RT: Reverse transcriptase.
SIV: Simian Immunodeficiency virus
TC: T cytotoxic cells
TDTH: Delayed type hypersensitivity T-cell
TH: T helper cell

Definitions
b2-Microglobulin: A protein associated with all class I MHC molecules on the surface of cells. Its serum levels may serve as prognostic indicator of progression to AIDS.

Acquired Immune Deficiency Syndrome (AIDS): A manifestation of infection with the human immunodeficiency virus (HIV) characterized by the presence of one or more illnesses/diseases as defined by the Centers for Disease Control (CDC).

Acute Infection: Describes the body response following entrance of HIV into the body. Symptoms may involve a mononucleosis or flu type syndrome which lasts for 2-6 weeks with fever, fatigue, vomiting, sweating, sore throat, lymphadenopathy, diarrhea, encephalopathy, peripheral neuropathy, occasionally pneumonia of undetermined origin and a red, blotchy rash on the truck. This period is associated with high levels of virus in the blood.

Anemia: A lower than normal number of red blood cells.

Antibody: Antibody functions as an effector molecule of the humoral response by binding to foreign antigen neutralizing it or facilitating its elimination.

Antigen: Molecules that are identifying characteristics of cells. Foreign antigens entering the body may evoke an immune response.

Antigen Presenting Cell (APC): Cells that express a particular type of membrane molecule called class II MHC and are able to deliver a co-stimulatory signal that is necessary for TH activation. These cells internalize antigen, and then re-express a part of that antigen, together with the MHC molecule, on their membrane. When a TH cell encounters an APC with class II MHC, it sends a partial activating signal called signal 1. When the co-stimulatory signal 2 is delivered, the TH cell becomes activated and begins to proliferate and secrete cytokines. APCs include macrophages, B cells, and dendritic cells (including Langerhans cells).

Antiretroviral drug: A drug that reduces the replication rate of HIV and is used to treat HIV-infected persons. The most commonly used are zidovudine, didanosine, and zalcitabine.

Asymptomatic Infection (Early to Middle Stage Infection): The period of infection following the acute infection phase where there is an absence of clinical manifestations of HIV infection. This is the clinically latent phase of disease and theoretically a person could remain in this state either because lytic infection is not induced, or the infecting strain of HIV is non-pathogenic in nature. During this period HIV is usually replicating and the immune system is responding to it.

Bacteria: Microscopic organisms that may cause disease in humans.

B-Lymphocyte: A type of white blood cell which is a component of the humoral immune system. B lymphocytes proliferate under stimulation from factors released by TH lymphocytes. When a B-cell encounters the foreign antigen for which it is membrane antibody specific, the cell will divide rapidly and its progeny will differentiate into memory B-cells and plasma cells. (see also Memory B-Cells, Plasma Cells, and Humoral Immunity). Plasma cells produce antibody molecules.

CD4 Molecule: A molecule displayed on several types of T-lymphocytes ( expressed in the highest concentration on the T helper cell) . It is the CD4 cells that are destroyed in HIV disease. CD4 serves as the major receptor for gp120 in HIV binding to host cells.

CD8 molecule: A molecule displayed on a subset of T lymphocytes. CD8+ T lymphocytes when activated are responsible for destroying altered self cells such as viral infected cells or cancer cells.

Cell Mediated Immunity: The branch of the immune system which defends the body against foreign organisms that live parasitically inside human cells, and cells that are foreign to the body such as cancer cells, virally infected cells and grafted cells. It is made up of T-lymphocytes. This type of immunity is especially important in host defense against intracellular bacteria and altered self cells. Both TH and TC cells can serve as the effector cells in response to antigen. This kind of immunity can only be transferred by immune T-cells. Cytokines secreted by TH (TDTH cells) can activate various phagocytic cells enabling them to more effectively phagocytize and kill microorganisms. As TC cells are activated by cytokines released by the TH cell, they become cytotoxic T-lymphocytes (CTLs) which are able to kill altered self cells. These cells play an important role in killing cells infected with viruses and tumor cells. Cell-mediated response recognizes epitopes displayed together with molecules of class II MHC on self cells. The recognition of an antigen/MHC combination by a specific T lymphocyte induces clonal proliferation into various T cells with effector functions, such as T helper and T cytotoxic cells and into T memory cells. Other types of cells contributing to the cell mediated immune response include specific cells - CD4+T lymphocyte subsets and CD8+T lymphocytes, and non-specific cells - macrophages, neutrophils, eosinophils and natural killer cells, all of which are dependent on high localized concentration of various cytokines.

Central Nervous System (CNS): The brain, spinal cord, and its covering (meninges).

Centers for Disease Control and Prevention (CDC): A branch of the U.S. Public Health Service that is responsible for monitoring the HIV/AIDS epidemic and carrying out efforts to prevent HIV infection.

Cellular Antiviral Factor (CAF): A cellular product produced by certain activated CD8 cells involved in the suppression of HIV replication without cell killing. These activated CD8 cells increase in HIV infected individuals. These cells seem to be predominate in long term non-progressors.

Class I MHC: A molecule found on all nucleated body cells. This is presented with antigen from an organism such as HIV that has infected a human cell. When these are found on the membrane of a cell, CD8+TC cells will recognize this antigen+class I MHC and kill the altered-self cell.

Class II MHC: A molecule found only on antigen presenting cells. This is presented with antigen from a foreign organism on the membrane of the antigen presenting cell. The CD4+TH cell recognizes this antigen+class II MHC and this leads to activation of the TH cell and The TH cell begins to divide and to secrete cytokines.

Co-Factor: A specific substance necessary for or which increases the probability of the development of disease in the presence of the basic etiologic agent of that disease. In HIV disease, some factors are clear, while others are suspected to increase the likelihood of disease progression.

Cytokines: Growth factors secreted from activated T-helper cells which play an important role in activating the immune response. Changes in the pattern of cytokine production can result in qualitative changes in the type of immune response that develops. In HIV disease they may create problems.

Cytopathic retroviruses: Members of the family of Lentiviruses that induce damage or death to cells. HIV may be grouped into this category. (see also Transforming Retroviruses)

Cytotoxic T-lymphocyte (CTL): Cells of the cell mediated branch of the immune system An activated form of a CD8+T lymphocyte (TC) that responds to altered self cells (such as HIV infected cells or tumor cells).

Delayed Type Hypersensitivity: A localized inflammatory reaction induced by cytokines secreted from activated TH cells. Onset of the reaction is delayed and there is often extensive tissue damage to the area. TDTH lymphocyte is one of the primary coordinators of delayed type hypersensitivity. It is specialized in defending the host against parasites and bacteria that live intracellulary in macrophages. The functional state of sensitized TDTH cells is assessed by doing a skin test. In patients with AIDS, the skin test reactivity towards a variety of common pathogens completely disappears and one way of monitoring immune decline in HIV infected individuals is to do periodic skin tests and look for a decline in positive reactions. It is these types of cells that is depleted with HIV. Many of the OIs seen in HIV disease are caused by intracellular parasites normally controlled by TDTH cells.

Dementia: Chronic intellectual impairment or loss of mental capacity.

Dendritic Cells: Antigen presenting cells with long membrane processes; some dendritic cells are found in the lymph nodes. Langerhans cells are dendritic cells found in the skin.

Diversity: The diversity of the immune system enables it to recognize billions of uniquely different structures on foreign antigens. Diversity enables the immune system to respond to foreign molecules that it has never even seen. It is estimated the immune system is capable of responding to 1011-1018 different antigens.

DNA polymerase: An enzyme that copies the single stranded DNA copy into double-stranded DNA.

Early HIV infection: The stage of HIV infection following the acute phase during which no major physical health symptoms are yet present, though psychological symptoms may be present and disruption of the immune system may be occurring.

Effector Cell: an activated T or B cell; effector B cells produce antibodies, effector T cells are CTLs

Envelope: The outermost layer surrounding the nucleocapsid and viral genome of HIV acquired from the infected host cell by a process called budding.

Enzymes: Body proteins that catalyze (initiate or speed up) specific chemical reactions but are NOT consumed in the process. Humans possess more than 7,000 different kinds of enzymes in each cell of the body.

Epidemic: Appearance of an infectious disease or condition which attacks many people at the same time, in the same geographical location, or more than the usual number of cases of a disease.

Epidemiology: The science concerned with defining and explaining the interrelationships of factors that determine disease frequency and distribution.

Erythropoietin (EPO): A hormone produced by the kidney that stimulates red blood cell production.

Fungus: A general term used to denote a plant-like class of microbes including mushrooms, yeasts and molds.

gp120: Glycoprotein 120. In HIV a combination of sugar and proteins which extend beyond the viral membrane and is associated with gp41. Plays an important role in HIV binding and entering host cells.

gp41: Glycoprotein 41. In HIV a transmembrane protein associated with sugar molecules, associated with gp120. Plays an important role in HIV binding and entering host cells.

Hematopoiesis: Refers to the formation and development of the red and white blood cells from stem cells. This process occurs in the bone marrow. Cytokines stimulate the proliferation and/or differentiation of various hematopoietic cells.

HIV-0: HIV-0 was recently identified from Cameroon and appears to be genetically 1/2 way between HIV-1 and HIV-2.

HIV-1: Is endemic in Central Africa, the Americas, Europe Asia and Haiti. It infects both humans and chimps but causes immune suppression only in humans.

HIV-2: A strain of HIV that is believed to be less pathogenic than HIV I. Mainly found in Western Africa. Has a lower affinity for CD4 cells and may account for the lower pathogenicity than HIV-1. Has a broader host range, infecting humans, chimps, macaques, and baboons.

Hospice: A health facility in which medical and mental health care are provided to a terminally ill client. The hospice philosophy emphasizes alleviating the client's discomfort and supporting the family in the grieving process.

Human Immunodeficiency Virus (HIV): The virus that causes AIDS.

Humoral Immunity: The branch of the immune system which produces antibodies. Derives its name in reference to the fact that immunity can be transferred from an immune individual to a non-immune individual by the transfer of serum antibody.

Iatrogenic: Adverse effect of prescription by physician. (physician caused)

Immune deficiency: A breakdown or inability of certain parts of the immune system to function, thus making a person susceptible to certain diseases which they would not ordinary develop.

Immune system: The mechanism of the body that recognizes foreign agents or substances, neutralizes them, and recalls the response later when confronted with the same challenge.

Inflammatory response: The sequence of events that take place when there is tissue damage caused by a wound or by invasion of pathogenic microorganisms.

Integrase: A viral enzyme that mediates the process of integration of the HIV DNA into the host cell genome.

Interferons : Anti-viral agents synthesized by activated T cells that have various roles in regulating immune functions. They binds to receptors on the membrane of other cells and induces synthesis of several cellular proteins which may inhibit viral replication in the uninfected cell.

Langerhans Cells: They are the immature form of dendritic cells of the monocyte/macrophage line and can be infected by HIV directly through mucous membrane and broken skin. It is also an antigen presenting cell.

Lesion: An area of altered tissue; the infected area or sore in a skin disease.

Leukopenia: A decrease in white blood cell count.

Lymph Nodes: Act as filters and are found at the junctions of lymphatic vessels. They contain a high concentration of lymphocytes, macrophages and dendritic cells. As an antigen is carried into the node by the lymph fluid, it is trapped, processed and presented together with class II MHC molecules, resulting in TH cell activation.

Lymphatic System: A physiological system that consists of an extensive network of thin vessels that resemble veins and parallels the circulatory system. The system also includes various organs to carry out its functions - bone marrow, thymus, spleen and lymph nodes. Its function is to filter and return interstitial fluid back to the circulatory system. Lymph fluid contains protein and a high concentration of lymphocytes.

Lymphocytes; A type of white blood cell produced in the bone marrow during hematopoiesis. They leave the bone marrow, circulate in the blood and lymph system and reside in various lymphoid organs. The features of specific/acquired immunity is mediated by lymphocytes. They have membrane receptors to recognize antigens. (see also Specific Immunity, B lymphocytes, T lymphocytes)

Macrophage: A non-specific phagocytic cell which displays a low level of CD4 molecules on its surface membrane. It does not die rapidly in the course of HIV infection and can harbor the virus protecting it from the immune system and serving as a reservoir from which the virus can be transmitted throughout the body, from one individual to another, or from one cell to another. This cell can also cross the blood-brain barrier making direct infection of brain cells possible.

Memory B-Cells: From the humoral branch of the immune system, memory B-cells are a type of B-lymphocyte that can have a long lifespan and continues to express the same membrane antibody with the same specificity as the original parent cell.

Memory: Special cells in the immune system have the job of remembering all the various antigens the host has ever encountered. The second time the immune system encounters the antigen, it will respond much more vigorously - much faster and much more intense.

Nucleoside Analogs: Antiviral drugs (e.g.. AZT) that try to mimic the building blocks of DNA or RNA to prevent viral replication by inhibiting DNA or RNA chain elongation. (At the same time, the analogs may also block DNA synthesis in normal cell division-especially in rapidly forming cells like RBCs and WBCs- potentially leading to anemia) .
Neopterin: A metabolite produced by macrophages following activation by gamma-interferon. Its levels in the blood stream reflects increased immune cell (macrophages and lymphocytes) activity and may serve as prognostic indicator of progression to AIDS.

Non-specific Immunity: Refers to basic resistance to disease that a species possesses. Includes anatomical barriers (e.g., skin, mucous membranes) and physiological barriers (e.g., pH, temperature, oxygen tension and various soluble factors.) as well as endocytic and phagocytic barriers.

Nosocomial: Hospital acquired disease.

Opportunistic infections (OIs): Illnesses caused by organisms that do not usually cause disease in a person with a healthy immune system. When an individual's immune system is compromised, such organisms may cause serious, life-threatening illness.

p24: A structural protein of the HIV nucleocapsid. The appearance of antibodies to p24 correlates with at least a somewhat effective immune response. When the antibody to p24 begins to decline, there is a corresponding increase in the appearance of p24 antigen in the serum which is indicative of increased viral replication and viral load.

Pathogen: A microorganism, or other substance capable of causing disease.

Persistent Generalized Lymphadenopathy (PGL): Is defined as lymph node enlargement of 1 cm or greater at two or more extra inguinal sites persisting for more than three months in the absence of a concurrent illness or condition other than HIV infection to explain the findings. Probably due to : normal swelling of the nodes in the filtration process during infection, hyperactivity of the B-cells (which are chronically activated for antibody production), direct destruction of the nodes’ germinal centers by infection with HIV, or the immune system response that damages the node.

Plasma Cells: From the humoral branch of the immune system, plasma B cells secrete antibody against a specific antigen. They live for only a few days but secrete more than 2,000 molecules of antibody per second.

Platelets: A component of blood responsible for blood clotting and sealing off wounds.

Primary Lymphoid Organs: Sites in the lymphatic system where B and T cells mature and acquire antigen specific receptors for antigen. Includes the bone marrow and thymus.

Protease Inhibitors: Very promising drugs which inhibit the activity of viral protease enzyme making it unable to cleave precursor proteins into viable viral proteins.

Protease: An enzyme which cleaves precursor polyproteins into individual, active proteins.

Provirus: The term given to a host cell that has HIV viral DNA incorporated into its own genome. It may remain in a latent state or be activated and transcribed into mRNA then translated into viral proteins. Normal cell division will result in 2 daughter cells with proviral DNA.

Reverse Transcriptase: An enzyme that reverse transcribes HIV RNA into DNA in order to integrate into the host genome.

Secondary Lymphoid Organs: Sites in the lymphatic system that trap antigens that have gained entrance into the body and provides a site for lymphocytes to interact with that antigen. Organs include lymph nodes, tonsils, adenoids, appendix, and interstitial Peyer’s patches.
Self/Non-Self Recognition: Refers to the fact the immune system can distinguish self from non-self. The immune system will attack only what is not self. This is essential because failure to do so can lead to fatal autoimmune disease.

Seroconversion: When a person's antibody status changes from negative to positive.

Specific Immunity: The acquired immune response that is capable of specifically recognizing and selectively eliminating foreign microorganisms or antigens. It differs from non-specific immunity in that it displays four important features: Specificity, Diversity, Memory and Self/Non-self Recognition).

Specificity: The ability for the acquired immune system to distinguish subtle chemical differences among foreign antigens. The immune system will recognize each of the proteins of HIV.

Spleen: This organ of the lymphoid system filters the blood and traps blood borne and antigens. It responds to systemic infections and contains macrophages, dendritic cells, T cells and B cells.

Stomatitis: Any of numerous inflammatory diseases of the mouth.

Syndrome: A group of signs or symptoms that characterize a particular disease.

T Cytotoxic Cells: TC. A type of T-lymphocyte (with CD8 molecules on its membrane surface) that recognizes antigen together with MHC molecules and (under the influence of TH derived cytokines) the T cytotoxic cell (TC) proliferates and differentiates into cytotoxic T-lymphocytes - (CTL) (see also Cytotoxic T-lymphocytes)

T lymphocyte: A white blood cell of the humoral and cell-mediated branch of immunity.

T-Helper Cells: A type of T-lymphocyte that displays the characteristic CD4 molecule on its membrane surface. It functions both as a part of the TDTH response, and as the activator of both the humoral and cell mediated immune responses. The T helper cell orchestrates the total immune response.

Transforming retroviruses: Viruses that induce changes in cell growth that may lead to cancer. HIV may be grouped into this category. (see also Cytopathic Retroviruses.)

Virus: A small microscopic organism that can only be seen with an electron microscope. Viruses cannot reproduce outside a living host cell.

Viral Load: The amount of free virus particles in the blood stream. This term is now used to describe the number of RNA copies/ml. of blood This number is used as a measure of viral activity and disease progression.


REFERENCES

Aboulafia, D.M. (1994). Human immunodeficiency virus-associated neoplasms. Cancer Practice 2(4), 297-306.

Auleb, A. , Kuby, J. (1997) AIDS: The Biology of a Modern Epidemic. San Francisco State University

Cohen PT, Sande MA, Volberding PA. The AIDS Knowledge Base, 2nd Edition. Little, Brown, 1994.

Flaskerud, P.J. Ungvarski (Eds.) HIV/AIDS: A guide to nursing care (3rd ed.), Ch.4 Philadelphia: W.B. Saunders.

Goldschmidt, R.H. & Dong, B.J. (1994). Current report - HIV treatment of AIDS and HIV-Related conditions 1994. Journal of American Board of Family Practice, 7-2, 155-178.

Grief, J. & Golden, B.A. (Eds.)(1994). AIDS care at home. New York: Wiley & Sons, Inc.

Kuby, J. Immunology, 2nd Edition. W.H. Freeman and Company, New York, 1991.

McCaffrey, M. & Beebe, A. (1989). Pain: Clinical manual for nursing practice. St. Louis: C.V. Mosby Co.

Project Inform. The HIV Drug Book. Pocket Books, 1995.

Sande MA, Volberding PA. The Medical Management of AIDS, 5th Edition. W.B. Saunders Company, 1997

U.S. Department of Health and Human Services (1994). Evaluation and management of early HIV infection. Clinical practice guideline. AHCPR Publication, No. 94-0572

U.S. Department of Health and Human Services (1994). Management of cancer pain. Clinical practice guideline. AHCPR Publication, No. 94-0592.

Ungvarski, P.J. & Stasts, J.A. (1995). Clinical manifestations of AIDS in adults. In J.H.

Walent, R.J. (1992). AIDS nursing: Patient care issues in the hospital setting. Oncology, 2-92, 131-137.


Index of Figures and Tables

Figure 1.1 Death Rates in U.S.
Figure 1.2 U.S. Statistics of HIV
Figure 1.3 Ethnic Distribution
Figure 1.4 HIV Virus
Figure 1.5 HIV Lifecycle
Figure 1.6 HIV Transmission methods
Figure 1.7 Immune System Overview
Figure 1.8 Typical Path of HIV
Figure 1.9 Direct Effects of the Virus
Figure 1.10 Estimated Global Distribution
Figure 1.11 Death Rates for Men
Figure 1.12 Death Rates for Women
Table 1.1 Cancers and Causative Agents
Table 1.2 1993 Revised Classification System for HIV Infection
Table 1.3 AIDS diagnosis based on percentage of CD4
Table 1.4 Clinical appearance of diseases
Table 1.5 KARNOFSKY PERFORMANCE STATUS CRITERIA
Table 1.6 Treatment regimens for HIV Disease


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