Answering the skeptics: Responses to arguments that HIV does not cause AIDS.

Myth: HIV cannot be the cause of AIDS because researchers are unable to explain precisely how HIV destroys the immune system.

Fact: A great deal is known about the pathogenesis of HIV disease, even though important details remain to be elucidated. However, a complete understanding of the pathogenesis of a disease is not a prerequisite to knowing its cause. Most infectious agents have been associated with the disease they cause long before their pathogenic mechanisms have been discovered. Because research in pathogenesis is difficult when precise animal models are unavailable, the disease-causing mechanisms in many diseases, including tuberculosis and hepatitis B are poorly understood. The critics' reasoning would lead to the conclusion that tuberculosis is not the cause of tuberculosis or that hepatitis B virus is not a cause of liver disease.

Myth: Behavioral factors such as recreational drug use and multiple sexual partners account for AIDS.

Fact: The proposed behavioral causes of AIDS, such as multiple sexual partners and long-term recreational drug use, have existed for many years. The epidemic of AIDS, characterized by the occurrence of formerly rare opportunistic infections such as Pneumocystis carinii pneumonia (PCP) did not occur in this country until a previously unknown human retrovirus -- HIV -- spread through certain communities.

Compelling evidence against the hypothesis that behavioral factors cause AIDS comes from recent studies that have followed cohorts of homosexual men for long periods of time and found that only HIV-seropositive men develop AIDS.

For example, in a prospectively studied cohort in Vancouver, 715 homosexual men were followed for a median of 8.6 years. Among 365 HIV-positive individuals, 136 developed AIDS. No AIDS-defining illnesses occurred among 350 seronegative men despite the fact that these men reported appreciable use of inhalable nitrites ("poppers") and other recreational drugs, and frequent receptive anal intercourse. Other studies show that among homosexual men and injection drug users, the specific immune deficit that leads to AIDS -- a progressive and sustained loss of CD4+ T cells -- is extremely rare in the absence of other immunosuppressive conditions. In the Multicenter AIDS Cohort Study, more than 22,000 T-cell determinations in 2,713 HIV-seronegative homosexual men revealed only one individual with a CD4+ T cell count persistently lower than 300 cells/mm3, and this individual was receiving immunosuppressive therapy.

In a survey of 229 HIV-seronegative injection drug users in New York City, mean CD4+ T cell counts of the group were consistently more than 1000 cells/mm3. Only two individuals had two CD4+ T cell measurements of less than 300/mm3, one of whom died with cardiac disease and non-Hodgkin's lymphoma listed as the cause of death. In another study, HIV-seronegative, long-term heroin addicts had mean CD4+ T cell counts of 1500/mm3, while eleven healthy controls had CD4+ counts of 820 cells/mm3.

Myth: The AIDS epidemic has been compounded by immunosuppressive effects of the medication AZT.

Fact: Placebo-controlled trials have found that AZT and related anti-HIV drugs can benefit patients by prolonging, for a year or two, the onset of new AIDS-related illnesses in HIV-infected individuals. Significantly, long-term follow-up of these trials, although not showing prolonged benefit of AZT, has never indicated that the drug increases disease progression or mortality. The lack of excess AIDS cases and death in the AZT arms of these trials effectively rebuts the argument that AZT causes AIDS.

In addition, many individuals who have never taken AZT or related drugs have developed AIDS, including people in the United States prior to the availability of AZT, and in Africa today where very few people receive AZT. Several studies suggest that life expectancy of individuals with HIV disease has increased since the use of AZT became common. One cohort study found that the time from seroconversion to death, a period not influenced by variations in diagnosing AIDS, has lengthened slightly in recent years. Even taking into account the benefits of improved PCP prophylaxis and treatment, if AZT were contributing to or causing disease, one would expect a decrease in survival figures, rather than an increase that coincides with the use of AZT.

Myth: AIDS among transfusion recipients is due to underlying diseases that necessitated the transfusion, rather than to HIV.

Fact: This notion is contradicted by a report by the Transfusion Safety Study Group (TSSG), which compared HIV-negative and HIV-positive blood recipients who had been given transfusions for similar diseases.

Approximately 3 years after the transfusion, the mean CD4+ T cell count in 64 HIV-negative recipients was 850/mm3, while HIV-seropositive individuals had average CD4+ T cell count of 375/mm3. By 1993, there were 37 cases of AIDS in the HIV-infected group, but not a single AIDS-defining illness in the HIV-seronegative transfusion recipients.

Myth: Cumulative exposure to contaminants in Factor VIII leads to CD4+ depletion and AIDS in hemophiliacs.

Fact: This view is contradicted by several large studies. For example, among HIV-seronegative patients with hemophilia A enrolled in the Transfusion Safety Study, no significant differences in CD4+ T cell counts were noted between 79 patients with no or minimal factor treatment and 52 with the largest amount of lifetime treatments. Patients in both groups had CD4+ T cell counts within the normal range. In another report from the Transfusion Safety Study, no instances of AIDS-defining illnesses were seen among 402 HIV-seronegative hemophiliacs who had received factor therapy.

Myth: The distribution of AIDS cases casts doubt on HIV as the cause. Viruses are not gender-specific, yet fewer than 10 percent of people with AIDS are women.

Fact: The distribution of AIDS cases, whether in the United States or elsewhere in the world, invariably mirrors the prevalence of HIV in a population. In the United States, HIV first appeared in populations of homosexual men and injection drug users, a majority of whom are male. Because HIV is spread primarily through sex or by the exchange of HIV-contaminated needles during injection drug use, it is not surprising that a majority of U.S. AIDS cases have occurred in men. Increasingly, however, women in this country are becoming HIV-infected, usually through the exchange of HIV-contaminated needles or sex with an HIV-infected male. As the number of HIV-infected women has risen, so too has the number of female AIDS patients in the United States. AIDS is now the leading cause of death among adults aged 25 to 44 in the United States, and the fourth leading cause of death of women in that age group.

In Africa, HIV was first recognized in sexually active heterosexuals, and AIDS cases in Africa have occurred at least as frequently in women as in men. Overall, the worldwide distribution of HIV infection and AIDS between men and women is approximately 1 to 1.

Myth: HIV cannot be the cause of AIDS because the body develops a vigorous antibody response to the virus.

Fact: This reasoning ignores numerous examples of viruses other than HIV that can be pathogenic after evidence of immunity appears. Measles virus may persist for years in brain cells, eventually causing a chronic neurologic disease despite the presence of antibodies. Viruses such as cytomegalovirus, herpes simplex and varicella zoster may be activated after years of latency even in the presence of abundant antibodies. In animals, viral relatives of HIV with long and variable latency periods, such as visna virus in sheep, cause central nervous system damage even after the production of antibodies.Also, HIV is well recognized as being able to mutate to avoid the ongoing immune response of the host.

Myth: Only a small number of CD4+ T cells are infected by HIV, not enough to damage the immune system.

Fact: New techniques such as the polymerase chain reaction have enabled scientists to demonstrate that a much larger proportion of CD4+ T cells are infected than previously realized, particularly in lymphoid tissues. Macrophages and other cell types are also infected with HIV and serve as reservoirs for the virus.

One group has reported that 25 percent of CD4+ T cells in the lymph nodes of HIV-infected individuals harbor HIV DNA early in the course of disease; other data suggest that HIV infection is sustained by a dynamic process involving continuous rounds of new viral infection and rapid turnover of an estimated 2 billion CD4+ T cells daily.

Myth: HIV is not the cause of AIDS because many individuals with HIV have not developed AIDS.

Fact: HIV disease has a prolonged and variable course. The median period of time between infection with HIV and the onset of clinically apparent disease is approximately 10 years, according to prospective studies of homosexual men in which dates of seroconversion are known. Similar estimates of asymptomatic periods have been made for HIV-infected blood-transfusion recipients, injection drug users and adult hemophiliacs. As with many diseases, a number of factors can influence the course of HIV disease. Factors such as age or genetic differences between individuals, the level of virulence of the individual strain of virus, as well as exogenous influences such as co-infection with other microbes may determine the rate and severity of HIV disease expression. Similarly, some people infected with hepatitis B, for example, show no symptoms or only jaundice and clear their infection, while others suffer disease ranging from chronic liver inflammation to cirrhosis and hepatocellular carcinoma. Co-factors probably also determine why some smokers develop lung cancer, while others do not.

Myth: Some people have many symptoms associated with AIDS but do not have HIV infection.

Fact: Most AIDS symptoms result from the development of opportunistic infections and cancers associated with severe immunosuppression secondary to HIV.

However, immunosuppression has many other potential causes. Individuals who take glucocorticoids and/or immunosuppressive drugs to prevent transplant rejection or for autoimmune diseases can have increased susceptibility to unusual infections, as do individuals with certain genetic conditions, severe malnutrition and certain kinds of cancers. There is no evidence suggesting that the numbers of such cases have risen, while abundant epidemiologic evidence shows a staggering rise in cases of immunosuppression among individuals who share one characteristic: HIV infection.

Myth: HIV does not fulfill Koch's postulates as the cause of AIDS.

Fact: Koch's postulates, formulated before the discovery of viruses, stipulate that an infectious agent must be found in all cases of the disease, the agent must be isolated from the host's body, the agent must cause disease when injected into healthy hosts, and the same agent must once again be isolated from the newly diseased host.

Koch's postulates have been fulfilled with laboratory workers and health care workers accidentally exposed to HIV, and in cases of AIDS developing after HIV seroconversion in blood transfusion cases. The postulates have also been fulfilled in baboons inoculated with HIV-2 and in macaques exposed to SIV.

Myth: AIDS is not exploding into the population, as one would expect if caused by HIV, a new virus.

Fact: HIV is spread by certain types of risk behavior and not by casual contact and is therefore not epidemic in the same way as influenza or the common cold. The more relevant issue is whether the spread of HIV and the appearance of AIDS correlate, and they do.

Myth: The spectrum of AIDS-related infections seen in different populations proves that AIDS is actually many diseases not caused by HIV.

Fact: The diseases associated with AIDS, such as PCP and Mycobacterium avium complex (MAC) are not caused by HIV but rather result from the immunosuppression caused by HIV disease. As the immune system of an HIV-infected individual weakens, he or she becomes susceptible to the particular viral, fungal and bacterial infections common in the community. For example, HIV-infected people in certain midwestern and mid-Atlantic regions are much more likely than people in New York City to develop histoplasmosis, which is caused by a fungus. A person in Africa is exposed to different pathogens than is an individual in an American city. Children may be exposed to different infectious agents than adults.

Myth: There is no AIDS in Africa. AIDS is nothing more than a new name for old diseases.

Fact: The diseases that have come to be associated with AIDS in Africa -- such as wasting syndrome, diarrheal diseases and TB -- have long been severe burdens there. However, high rates of mortality from these diseases, formerly confined to the elderly and malnourished, are now common among HIV-infected young and middle-aged people. In a recent study in rural Uganda, adolescents and young adults testing positive for HIV antibodies were 60 times more likely to die during the subsequent two-year observation period than otherwise similar persons who tested negative. In a study in Zaire, infants with HIV infection had an 11-fold increased risk of death from diarrhea compared with uninfected children. Elsewhere in Africa findings are similar.