HIV DISEASE*

Joy Volodkevich Koenig, M.D., M.S.
© 1993

Acquired Immune Deficiency Syndrome (AIDS) is the medical and legal terminology that refers to a collection of life-threatening medical conditions which develop as a result of infection with the Human Immunodeficiency Virus (HIV). HIV is a recently identified virus which destroys the human immune system by incorporating its genetic material into specific immune system cells, thereby destroying the cells designed to protect us from disease. HIV was identified by scientists in 1983, approximately 2 years after the first clusters of HIV-related diseases, Kaposi's sarcoma and Pneumocystis carinii pneumonia, were identified in Los Angeles, New York City, and San Francisco. Now, evidence of HIV infection is found on all continents and in more than 150 countries worldwide. HIV is thought to have arisen by mutation from a remarkably similar animal retrovirus, the simian T-lymphotropic virus. The introduction of HIV into the U.S. population will probably never be definitively identified. Unfortunately, those driven by anger and fear due to the fatal nature of the infection continue the circulation of unproven theories and blame for the virus's presence in our country.

The specific infections, malignancies and clinical signs which are used to classify HIV-infected individuals as having AIDS, continue to evolve as scientists learn more about the nature and treatment of this intricate infection. The psychological, social and economical devastations that occur secondary to HIV infection greatly burden the individual, our communities and the U.S. health care system. Decisions based on personal fear, morals and politics have sometimes turned AIDS into a battleground for individual's rights versus the need and desire to protect public health. As a society, we need to accept and integrate those whose sexual and drug use behaviors differ from the perceived majority, and acknowledge the variety and prevalence of these behaviors among all of us, whether we present the outward appearance of heterosexual, bisexual or gay. This will happen when we acknowledge that we cannot force people to behave in ways that make us comfortable; we each have a right to claim our individuality. Public attitude about AIDS and risk factors associated with AIDS will continue to play a crucial role in our ability to respond to this epidemic, and will therefore change the "natural history" of this epidemic in the United States.

We need to combat fear with education and the enforcement of laws to protect all of our rights. We must also begin to accept and combat the link between poverty, substance use and addiction and HIV. This chapter is intended to be a small first step towards knowledge about this devastating epidemic and who it affects, in a hope that those having this knowledge will understand, accept and help those who are infected with and affected by HIV infection.

Due to the rapidly increasing knowledge about HIV infection, some of the information contained in this chapter may already be inaccurate, particularly the medical consensus regarding treatment. Therefore, the reader is referred to Appendix A for organizations from which to obtain the most current information and assistance.

* Written for the American Civil Liberties Union publication, "The Rights of Persons Living with HIV/AIDS: A Guide for PWAs and Their Advocates"

WHAT IS HIV?

Viruses are packages of genetic material which require the protein-manufacturing abilities and resources of other cells to reproduce and survive. In many ways, viruses can be considered microscopic parasites. The Human Immunodeficiency Virus (HIV) contains a single chromosomal strand of genetic material. The chromosome is divided into approximately 10 genes which code for the structural proteins used to produce new viruses and the various proteins involved in regulating cell activity. HIV is a retrovirus, which means it encodes its genetic material in the form of a protein called ribonucleic acid (RNA). In order to affect human cells, HIV must first use a specific enzyme (reverse transcriptase) to translate its RNA into deoxyribonucleic acid (DNA), then incorporate this new DNA into the DNA of human cells using the enzyme endonuclease. The viral RNA and enzymes are surrounded by a protein layer, forming the viral core. A specific protein contained in this layer, p24, can be measured and is associated with disease progression. The outer shell of the virus contains twoglycoproteins, gp120 and gp41, which help the virus recognize and attach to the CD4 protein sites present on the surface of some types of human immune system cells, most frequently the T-lymphocyte helper cells and macrophages.

Outside of the body, HIV is very fragile because it requires living cells to survive and multiply. HIV cannot pass through unbroken skin, and is very sensitive to soap, alcohol, bleach and heat. A 1:10 dilution of household bleach rapidly inactivates HIV, and is useful in disinfecting surfaces contaminated with potentially infectious materials.

HOW IS AIDS DIFFERENT FROM HIV INFECTION?

AIDS is the end-stage manifestation of HIV infection. The term AIDS arose before scientists knew that HIV caused the illnesses being seen. The federal Centers for Disease Control created the term "Acquired Immunodeficiency Disease" or AIDS as a mechanism to count and track patients who were experiencing the various severe, life-threatening illnesses secondary to severely suppressed immune function. The word "acquired" was used to distinguish this group of diseases from immune system dysfunctions that are present at birth. All patients had laboratory tests indicating a failing immune system, or "Immune Deficiency". The term "Syndrome" means a collection of signs and symptoms occurring together. Through studying the blood and tissues of people who had these similar characteristics, researchers were subsequently able to identify the presence of HIV. In general, the acronym "AIDS" continues to refer to the end stage severe manifestations of HIV infection. However, in recent years the definition of AIDS has changed as the knowledge of the disease has increased, and the use of the term "AIDS" without clarification can result in confusion and misunderstanding.

WHO HAS HIV and AIDS?

HIV infection is a world-wide pandemic. The World Health Organization (WHO) and the federal Centers for Disease Control (CDC) estimate that between 9 and 11 million persons world-wide are infected with HIV, including over 1.5 million persons in the United States. Atthe beginning of 1992, there were at least 210,000 reported AIDS cases in the United States, with the second hundred thousand cases occurring in just 26 months.

The demographic distribution of HIV and AIDS varies dramatically among countries, genders, ethnicity and lifestyles and is steadily shifting. Sub-Saharan African countries have over six and a half times the number of adult HIV infections as North America. In the United States, gay and bisexual men are gradually representing a smaller proportion of cases, as rates in injecting drug users, their sexual partners and children claim an increasing percentage of HIV infection and AIDS. The prevalence of HIV acquired from heterosexual partners will increase as the prevalence of infection increases in bisexual men and their female partners. Currently, 85% of HIV-infected persons live in metropolitan areas with populations over 500,000, but rural populations are becoming increasingly affected.

Communities of color have acquired HIV at a disproportionate rate, in part due to their inequitable link to poverty, substance use and addiction, premature illness and disease (morbidity), and barriers to appropriate health care and funding. In this country, discrimination and cultural inadequacies related to data collection and prevention education have also contributed to the uneven distribution of HIV. Of particular concern is that racial/ethnic groups are claiming an increasing proportion of total AIDS cases. Currently, over 45% of reported AIDS cases have occurred among racial/ethnic minorities although they are only about 20% of our population. Almost 80% of children less than 13 years old who have AIDS are children of color.

The incidence of HIV infection continues to rise dramatically. Infection with HIV is still considered a fatal illness, although many clinical regimens have been developed to effectively treat and prevent or delay the onset of AIDS. It is this fatal aspect of AIDS that generates much of the fear and hysteria surrounding the HIV epidemic.

HOW DOES HIV CAUSE DISEASE?

The human immune system is a complicated network of checks and balances involving numerous highly specific cells, proteins and chemicals. HIV attacks and destroys immunesystem cells which contain CD4 receptor sites. T-lymphocyte helper cells are responsible for activating the immune system when an infectious agent is present by multiplying and outnumbering T-lymphocyte suppressor cells. The immune system is de-activated when T-lymphocyte suppressor cells outnumber helper cells. Since HIV selectively destroys helper but not suppressor cells, the immune system remains inactivated even in the presence of recognized infectious agents. Organisms such as yeasts, bacteria and protozoans usually kept to low numbers by healthy immune systems, can now take the opportunity to multiply unchecked and cause disease. Normally CD4 cell counts range from 800 - 1200. Persons with CD4 cell counts between 200 and 500 are moderately immune suppressed and may develop minor infections. Persons with CD4 cell counts of less than 200 are considered severely immune suppressed and are at a high risk for developing life-threatening opportunistic infections.

Macrophages also contain CD4 receptor sites and are susceptible to HIV attack. Macrophages are responsible for scavenging infectious agents, and are capable of crossing the blood-brain barrier. Some HIV-related diseases are caused by unintentional damage to tissues containing HIV-infected macrophages.

HOW ELSE DOES THE IMMUNE SYSTEM RESPOND TO HIV INFECTION?

When a person is exposed to an infectious agent, the body's immune system responds by producing antibodies and customizing certain lymphocytes to help arrest infection and recognize and prevent future infections with the same invader. Most persons who become infected with HIV begin with a healthy immune system, and begin to develop antibodies to HIV within a month of acquiring infection, regardless of the presence of initial signs and symptoms of illness. It takes at least 4 - 12 weeks and as long as 6 months for a sufficient quantity of antibody to develop before testing can detect the presence of anti-HIV antibodies. This time period is referred to as the "window period". In many illnesses, such as measles and mumps, antibodies serve to neutralize infection; however, in the case of HIV, antibodies serveas a marker to identify persons who have been infected with HIV, but do not ultimately prevent illness.

HOW IS HIV TRANSMITTED?

Although many routes of HIV transmission are theoretically plausible, epidemiologic evidence has supported only three mechanisms of transmission among human populations. It is important to know that exposure to the virus does not always result in infection with the virus. The virus has to be present in sufficient quantities and have direct access to the bloodstream in order to enter the body and cause infection. Certain types of behavior and conditions increase the efficiency of viral transmission, as outlined below.

Sexual contact is the most common mode of HIV transmission. For those who practice it, passive-receptive and insertive anal intercourse carry the greatest risk for both men and women, and are enhanced by rectal douching. Vaginal intercourse also confers high risk. Biologic characteristics cause male-to-female transmission to be at least 3 to 5 times more efficient than female-to-male transmission. Little is know about female-to-female transmission. Case reports of transmission from oral-genital contact have been anecdotally reported, and although this route of transmission is currently thought to be low risk, it has not been well studied.

HIV is efficiently transmitted by the transfusion of infectious blood products and transplant of infectious tissue, the inoculation of infectious blood, and through the exposure of mucus membranes and non-intact skin to infectious material. Most transfusion and transplant-related transmission occurred prior to the development of the HIV-antibody test in 1985, and only occurs rarely now. Voluntary self-exclusion criteria for potential blood and organ donors was instituted in 1983 and has recently been revised to reflect current knowledge of high-risk behaviors, and HIV antibody tests used to screen human products have been refined and are used more broadly.

Inoculation transmission continues to occur through the sharing of drug injection equipment (needles and syringes) and occupational needlestick injury. Exposure to mucus membranes and non-intact skin primarily occurs among those providing medical or first-aid services such as nurses, doctors, first responders (fire, police, and ambulance personnel), and those whose work involves exposure to human body fluids (morticians and laboratory technicians).

The third route of transmission is called vertical transmission, or the transmission of infection from an infected mother to her newborn infant. An estimated 25% of HIV infected mothers transmit their infection perinatally to their infants. The rate of transmission appears to increase with advancement of disease, and may vary with the strain of HIV carried by the mother. Although transmission through breast milk has been shown, this route of transmission appears to occur at very low frequencies in the United States.

WHAT FACTORS INFLUENCE TRANSMISSION?

An individual's risk of acquiring HIV infection is increased by several factors. Risk increases with the number of sexual or needle sharing encounters a person has with an infected person or persons. Choosing partners from among groups with a higher prevalence of HIV infection, such as prostitutes or injecting drug users is more likely to result in exposure to the virus. The presence of ulcerative lesions and irritation caused by syphilis, herpes and other sexually transmitted diseases increases HIV's access to the bloodstream.

Straightforward, scientifically accurate information about HIV infection and AIDS is the most effective deterrent to HIV transmission. This information needs to be presented in a culturally and age-appropriate manner during late childhood and/or early adolescence - before or concurrent with a child's awareness of and experimentation with sexual and drug using behaviors.

Sexual abstinence, refraining from injecting drug use, and avoiding the receipt of infectious human products reduce or eliminate risk, but are not always realistic, obtainable or desired options. Practicing safer sex (always correctly using latex condoms and dental dams with water-based lubricants, engaging in lower risk sexual behaviors, choosing partners without high-risk behaviors), not sharing equipment used for injecting drugs or bleaching syringes and needles when sharing injecting drug works, and adhering to universal precautions in work settings all effectively reduce but do not eliminate the risk of transmission.

Certain options do not decrease individual risk, including douching, diaphragms, birth control pills, IUDs, penile withdrawal before ejaculation, and unilateral monogamy.

HOW IS HIV NOT TRANSMITTED?

Fear of lethal illnesses creates an unrealistic request for absolute certainty and feeds public concerns that science may be wrong or that government officials are hiding critical information. Sufficient quantity and concentration of live virus and an opportunity to enter the bloodstream are necessary for infection to occur; therefore, many routes which seem possible in theory cannot occur in practice because of these necessary co-factors.

HIV is not transmitted through the air or by casual or non-sexual contacts such as hugging, cuddling, body massage, hand shaking, dry kissing, coughing, sneezing, sharing food, glasses, dishes and utensils, changing diapers, touching doorknobs, sharing telephones, bed linens, towels, toilets, furniture, or using swimming pools and hot tubs. Mosquitoes and other bugs are incapable of transmitting HIV, and HIV transmission has never been associated with donating blood or food handling. Even though very small amounts of the virus can be present in saliva, behaviors such as biting, scratching and spitting may appear possible in theory but have never been shown to transmit HIV.

WHAT IS THE NATURAL HISTORY OF HIV INFECTION?

HIV disease includes a wide spectrum of symptoms and illnesses. Symptoms of initial infection are non-specific (low grade fever, rash, irritability, muscle and joint pain, lymph node enlargement and cramping diarrhea) and occur within weeks of exposure to the virus. About 80% of infected persons report having this initial illness. Initial infection is usually followed by a prolonged latency period during which the person experiences no HIV-related symptoms but is capable of transmitting the infection to others. Most HIV infected persons are currently in this symptom-free stage, which typically lasts between 2 and 10 years. Some infected persons will subsequently develop a persistent enlargement of lymph nodes (persistent generalized lymphadenopathy) before the development of other HIV-related diseases such as cancers (Kaposi's sarcoma, non-Hodgkin's B-Cell lymphoma, Hodgkin's disease, primary central nervous system lymphoma), dementia, nutritional wasting syndromes, and a wide rangeof mild to life-threatening bacterial, fungal and viral infections. Although many infected persons will follow this progression from asymptomatic to opportunistic infections or cancer and death, some HIV-infected persons progress directly from asymptomatic infection to life-threatening illness, and others have lived symptom-free for more than 10 years.

Survival after diagnosis has increased two-fold in industrialized countries, and appears to be related to the use of antiviral and prophylactic (preventive) drugs as well as access to overall health care. However, HIV disease remains an incurable and fatal illness. About half of untreated HIV infected persons will progress to AIDS within 10 years. Over half of all people diagnosed with AIDS die within two years of their diagnosis. The latent (symptom-free) period of HIV infection may vary depending on the infectious "dose" received, the virulence (strength) of the strain, rate of viral replication, and access to adequate health care and nutrition.

WHAT ARE THE COMMON HIV-RELATED OPPORTUNISTIC INFECTIONS?

Most HIV-related disease results from compromise of the immune system. Pneumocystis carinii pneumonia (PCP) is a lung disease caused by a common yeast carried since childhood by most North American adults, but kept under control by healthy immune systems. Candidiasis is caused by the overgrowth of a yeast commonly found in the gastrointestinal tract and the vaginal tract. It can cause lesions of the tongue, mouth, throat, and intestinal and vaginal tracts, and may cause symptoms of chest pain and burning if the esophagus is involved. Cryptococcus meningitis is an infection of the fluid surrounding the brain and spinal cord caused by a yeast, and producing meningitis with symptoms of fever, headache and neck stiffness. Cryptospiridial diarrhea results from colonization of the intestinal tract with a protozoan, producing severe watery diarrhea, abdominal cramps, malnutrition and weight loss. Toxoplasmosis is a protozoal disease which effects many body systems, but most importantly can form pockets of infection (abscesses) in the brain, producing a variety of neurologic symptoms dependant on what area of the brain is effected. This protozoan can be found in cat droppings and contaminated meat, and sometimes producesdisease in individuals with normal immune systems. Cytomegalovirus is a viral infection which can cause initial or re-activated disease, most commonly lung infection and blindness.

While not considered opportunistic, several diseases such as tuberculosis (TB), salmonella, herpes varicella zoster (chicken pox and shingles), vaginal candidiasis, pelvic inflammatory disease (PID), human papilloma virus, and certain ulcerative sexually transmitted diseases including syphilis and genital herpes, appear to manifest differently and may take a more aggressive course in HIV-infected persons.

WHICH OF THESE OPPORTUNISTIC DISEASES ARE CONTAGIOUS TO PEOPLE WITH NORMAL IMMUNE SYSTEMS?

Most organisms that cause opportunistic infections in HIV-infected persons are ubiquitously present and do not cause disease in people with normal immune function. However, salmonella, tuberculosis, herpes simplex, and herpes varicella zoster may be transmitted to and cause disease in persons with normal immune function. Tuberculosis has become an increasing concern for several reasons. Several strains have recently developed that are resistant to most if not all the drugs currently available to treat TB, and persons with TB are often in prolonged close contact with other HIV-infected persons through hospitalization, incarceration or aggregating in homeless shelters.

WHAT OTHER DISEASES ARE ASSOCIATED WITH HIV INFECTION?

HIV-related nervous system illnesses and symptoms such as dementia, inability to concentrate and behavior changes are believed to result from the immune system's release of toxic chemicals targeting HIV-infected macrophages. Macrophages are found in blood and lymph fluids and can cross the blood-brain barrier by moving through capillary pores. HIV only crosses the blood-brain barrier if contained within a macrophage. HIV can also effect the spinal cord resulting in muscle weakness, paralysis and spasticity of the limbs, and loss ofbowel and bladder control. If nerves outside of the central nervous system are effected (peripheral nerves), limbs can become weak or painfully overly sensitive.

HIV can also cause gastrointestinal problems such as malnutrition and diarrhea by inducing anatomical changes in the lining of the small intestine and interference with the production of digestive enzymes. Food becomes only partially digested and poorly absorbed leading to diarrhea and a profound fatal weight loss. This manifestation of HIV infection is referred to as "slim disease" or "wasting syndrome".

HIV-associated cancers are similar to those cancers seen in other acquired and congenital immune deficiency diseases. However, recent scientific evidence suggests that mechanisms other than the loss of immune function are involved, and that concurrent infection with other agents may be required for the development of some of these cancers. These malignancies include Kaposi's sarcoma (proliferation of cells lining blood and lymphatic vessels), primary central nervous system lymphoma, specific types of non- Hodgkin's lymphoma, and atypical presentations of Hodgkin's disease. Cervical cancer in HIV infected women may be more difficult to identify through Pap testing and the course of disease may by influenced by HIV infection.

HIV is also associated with certain heart diseases, kidney abnormalities, liver failure, night sweats, and anemia.

DOES THE PRESENTATION AND PROGRESSION OF HIV DIFFER?

Several conditions alter the presentation and progression of HIV disease. Progression is related to age at time of infection. Infants and those over age 50 tend to progress more rapidly. Progression is also related to viral strain. This virus has an uncanny ability to rapidly and constantly redesign its surface, even after initial infection. Some of these strains are more virulent than others, causing quicker progression. For similar reasons, persons acquiring their infection from someone with more advanced disease are more likely to have a faster progression of symptoms.

HIV disease presents and progress differently in homosexual men, heterosexual men and women, children, adolescents and substance users. Substance users often have poor nutrition and limited access to substance abuse treatment and health care. Women who abuse substances may fear removal of their children from the home, an effective barrier to seeking health care. Crack houses and homelessness may increase exposure to diseases such as tuberculosis and salmonella, exposing addicts to a higher risk for acquiring secondary infections. Infants and young children have immature and developing immune systems, accelerating the progression of HIV. Adolescents often see themselves as invincible and immune to acquiring HIV, and often progress to advanced disease before denial of risk can be overcome. Persons who acquire infection through an inoculation of a large viral dose, such as hemophiliacs and drug users, tend to progress more rapidly.

Although women now comprise over 11% of reported AIDS cases in the United States, little is known about the progression and treatment of HIV disease among women, partly because studies on the natural history of HIV disease and clinical trials have often excluded female patients. Parenting and caretaking responsibilities can serve more often as barriers to health care for women than men. It is not certain whether women and men have the same rates of specific opportunistic infections, whether gender-specific death rates are different, and whether progression of disease is faster among women. If so, are differences attributable to true biologic or physiologic differences, a differential access to health care, or differences in how the virus was acquired? Twenty-five percent of gay men and only 3% of women present with Kaposi's sarcoma as their initial serious illness. We do not know the reason for this gender difference.

Several clinical signs can predict the progression of HIV infection. CD4 counts predictably decline as HIV infection progresses. Since an individual test values can be temporarily low during new infections, care needs to be taken in interpreting an individual test result. A CD4 count of less than 200 cells/mm³ is associated with a 30% chance of developing AIDS in one year and an almost 90% chance of developing AIDS in 3 years. Measurements of p24 antigen, the protein in the viral core, are not widely available, but are useful in predicting progression. A positive p24 antigen indicates a fourfold increased risk of AIDSdeveloping within 3 years. Another protein, Beta-2-microglobulin, increases with the impending onset of AIDS.

HOW IS HIV INFECTION DIAGNOSED?

A diagnosis of HIV infection can often be made based on clinical signs and symptoms of HIV-related diseases and infections. In those persons with less specific manifestations, such as dementia or wasting syndrome, and in asymptomatic persons who suspect infection based on potential exposure, diagnosis needs to be confirmed through pairing the medical and social history with a blood test detecting the presence of antibodies to HIV. Testing must be accompanied by appropriate counseling before and after testing, and must be performed confidentially or anonymously.

No laboratory test is 100% accurate, whether for diabetes, kidney disease or HIV. All tests have a sensitivity (probability that the test will be positive if disease is present) and a specificity (probability that a test will be negative if no disease is present) less than 100%. Laboratories will use more than one test in parallel or sequence to improve the accuracy of testing, but false-positive and false-negative determinations occur infrequently. HIV is usually tested for sequentially, using an enzyme-linked immunoabsorbent assay (ELISA), repeated and followed by and a Western blot test. The ability of the tests to accurately identify truly infected persons depends on the reliability and accuracy of laboratory methods, the amount of antibody present in the persons bloodstream, and the persons individual risk for having acquiring infection. Laboratories should only use FDA-approved and regulated products, and the test should be done with awareness of the window period, when infection is present but antibodies levels are too low to be detected. If a person at low risk of HIV infection has a positive determination, testing should be repeated four to eight weeks later to rule out the possibility the test was falsely positive. For many reasons, mass screening of the general population under any label (pre-marital, pre-natal, pre-employment, high-risk employment) is unlikely to be useful. Most are unaware that the rate of false positive test results increase when used in lower-risk populations, and that negative test results for persons who are infected but in the window period can give a false sense of safety to these individuals. Importantly, there is still great potential for inappropriate and misuse of HIV test results.

WHO SHOULD BE COUNSELED AND TESTED?

The HIV antibody test is the only way to tell whether HIV infection is present in asymptomatic persons. Persons who have engaged in behavior with a high risk of HIV transmission should consider counseling and testing to learn how to reduce transmission of infection to others and to appropriately access preventive health care if infected. Persons are more likely to appropriately seek counseling and testing if fear of discrimination doesn't exist. It is important for counseling to be age and culturally appropriate. Before testing is done, it is important to consider the individual's unique situation regarding recovery from substance addiction and the availability of an effective social support system.

HOW IS HIV TREATED?

HIV infection highlights the necessity of practicing medicine as both an art and a science. The relationship between clinician and patient works best as a partnership, and requires a non-judgmental attitude toward sexual behavior, drug use, and often requires a willingness to accommodate cultural and ethnic customs, non-Western medical treatments and reproductive decisions that might be different from the clinician's. Providers need to encourage patients to maintain and develop supportive relationships with other providers, family members and friends. Care-takers need to be sensitive to hope and how "news" is given to persons living with HIV infection, in order convey that help is being given to live with the disease rather than die from it, yet be prepared to address issues of death and dying. Health care providers need to admit when answers are unsure or unknown, and allow the patient some control over treatment decisions. Providers need to remember that although some patients may have contributed to their illness through behavior, they aren't responsible for having an illness, and that often behaviors relating to sexual orientation and addiction are not driven by free choice. Persons providing care for HIV-infected patients need to be knowledgeable of the clinical trial and drug development systems, and need to know how togain access to service provider information networks which assist with appropriate referrals within the heath care system.

There are many avenues by which drugs can prevent or treat HIV infection and related diseases. The Pharmaceutical Manufacturers Association's 1991 survey reports at least 88 HIV-related drugs currently in testing. These drugs fall into several categories. Antivirals are drugs designed to reduce or prevent viral replication. They can act by preventing attachment of HIV to the CD4 receptor site, or by interfering with the enzymes needed for gene copying. FDA has approved 3 drugs in this category: azidothymidine (AZT), also known as zidovudine (approximately one-third of patients are intolerant to the severe toxic side-effects of this drug), didanosine (ddI) and the combination of dideoxycitidine (ddC) and AZT. Drugs which boost the immune system are called immunomodulators and include 2 FDA-approved products, interferon alfa-2a and interferon alfa-2b. These drugs are used in the treatment of Kaposi's sarcoma. Anti-infectives (which include antibiotics) are designed to combat or prevent the specific opportunistic infections that are frequently associated with HIV infection. Medications are usually required long term for suppressive treatment, and are needed to treat multiple and concurrent infections. Most FDA-approved drugs fall into this category, including pentamidine and trimethoprim sulfamethoxazole used to treat and prevent PCP, fluconazole used to treat cryptococcus and candidiasis, ganciclovir and foscarnet used to treat cytomegalovirus retinitis, and pyrimethamine used to treat toxoplasmosis. Epoetin alfa is an FDA-approved drug to treat the anemia secondary to bone marrow suppression, a side effect of AZT therapy. A detailed description of dosing and side-effects is beyond the scope of this chapter; however, Appendix B contains a listing of many current treatment alternatives.

Eight pre- and post-exposure vaccines are currently being studied in small clinical trials for their safety and their ability to produce antibodies to HIV. Pre-exposure vaccines are designed to prevent infection, while post-exposure vaccines help boost the immune system to stop or delay the progression of disease after infection. Vaccines need to provide effective protection against free virus in the bloodstream as well as cells that are already infected with HIV.

WHAT ARE CLINICAL TRIALS?

Clinical trials are research studies designed to determine whether a promising treatment is safe and effective. Carefully conducted clinical trials are the fastest and safest way to learn which treatments work. For most diseases, being part of a clinical trial is an adjunct to standard medical treatment and care. However, in the cases of cancer, HIV infection and other diseases for which there are few proven therapies, clinical trials are usually synonymous with care. Unfortunately, conflict occurs because of the differing goals of treatment and research. To ensure scientific validity, trials must follow strict protocols, often restricting who is eligible to participate and the study may not always provide the best treatment for the individual, and may even be harmful. In addition, insurance and medicaid may not cover the costs of research-related treatment.

Clinical trials are offered at many large medical centers and hospitals, through community health centers, private physicians and clinics, and at specialized research centers such as the National Institutes of Health. The federal government has several programs related to clinical trials including the AIDS Clinical Trials Group (ACTG), a cooperative network of university-based research hospitals, the Division of AIDS Treatment Research Initiative, with a focus on safety (Phase I) studies and the Community-Based Clinical Trials Network, comprised of treatment research programs in cities using community providers and health center consortia. The American Foundation for AIDS Research (AmFAR) publishes a quarterly publication on available clinical trials in addition to providing funding for AIDS-related research. Clinical trials are also sponsored by private research institutes and pharmaceutical companies. Since many persons cannot meet the strict requirements for enrollment in many of these studies, alternate mechanisms for access to these experimental treatments have been evolved, only some of which are FDA-approved. Many of these are detailed in later chapters. Open label studies or compassionate use protocols involve the release of an investigational new drug to individual patients before efficacy has been established. Parallel tract involves monitored access to investigational new drugs for persons unable to participate in controlled trials. Buyer's clubs are organizations which distributeexperimental and FDA-approved drugs, often through mail-order. Sources for clinical trials and treatment information are listed in appendix C.

WHAT NON-DRUG THERAPIES ARE AVAILABLE FOR HIV-RELATED DISEASE?

Appropriate nutritional support is critical in the therapy of HIV-related disease, both in prevention and treatment of illness. Psychotherapy and stress reduction therapies including relaxation therapy, creative visualization, massage therapy, aroma therapy, and pet therapy can be useful adjuncts to traditional medical care. Although scientific evidence is scant or lacking for treatments such as acupuncture, herbal products and many holistic health practices, many of these do no harm and may be helpful. Persons with HIV infection should be wary of treatments which make definitive medical claims without scientific documentation. Health fraud is a common among AIDS-related treatments. Some advertised and foreign therapies are extremely costly and may be harmful rather than helpful, especially if used in place of accepted treatments. All therapeutic modalities should be discussed with a reputable health care provider, especially to prevent the possibility of unexpected life-threatening interactions from combining incompatible therapies.

CLAIMING THE RIGHT TO GOOD HEALTH

Everyone has the right to good health, but many people don't realize that this right has to be actively claimed in order to be exercised. Our actual physical health can be modified by our mental, emotional, and spiritual well-being. People living with HIV need to claim their right to good health by accessing the resources to which they are entitled, nurturing their self-esteem, and by building effective relationships with caring providers, family, friends and neighbors. Stepping out of a victim role and into the role of self-advocacy is a necessary and sometimes difficult first step. Friends and family can often help with advocacy and learning self-advocacy. Community activism can serve as an effective method of self-advocacy, and is an outlet which has greatly increased the availability of national and local resources for HIV-infected persons.

Advocates for persons infected with HIV need to help combat discrimination against persons with HIV, and need to open the door to resources. This needs to be done on both an individual and community level. Using gentle correction to educate neighbors and co-workers about overt or subconscious discriminatory remarks or behaviors can have a major impact on how a person with HIV is accepted in a community. Individuals can raise the awareness of unmet needs to business and community leaders through encouraging work place educational programs and fund raising efforts for HIV. There are endless ways to make a personal difference in the life of someone who has HIV, such as providing respite care, delivering groceries, preparing meals, helping with laundry and housekeeping, and providing transportation to appointments. Most importantly, we can give persons with HIV our moral support. People are social beings, and thrive on both giving and receiving. Something as simple as a handful of dandelions can bring a message of caring that has a measurable effect on the well-being of both the giver and receiver. Numerous organizations have programs which reach people with HIV disease. Existing programs include those which advocate for fair housing and loans, protect employment, provide educational, medical and social support, and raise funds. Business and individual volunteers are almost always the cornerstones of such organizations.

Through the advances of medicine and science, HIV disease will most likely become a chronic, treatable illness, and may someday be largely preventable. Until that time, we each have a responsibility to give persons at risk for and infected with HIV our understanding, compassion, and acceptance. We need to advocate for those who cannot advocate for themselves, and acknowledge that each person has a right to individuality and a right to good health.