http://www.cappbc.org/index.cfm?fuseaction=pages.EvidenceHIVcausesAIDS%20&
Evidence that HIV causes AIDS

   Acquired immunodeficiency syndrome (AIDS) was first recognized in
1981 and has since become a major worldwide epidemic. AIDS is caused
by the human immunodeficiency virus (HIV). By leading to the
destruction and/or functional impairment of cells of the immune
system, notably CD4+ T cells, HIV progressively destroys the body's
ability to fight infections and certain cancers.

   This document summarizes the abundant evidence that HIV causes
AIDS. Questions and answers further on in this document address the
specific claims of those who assert that HIV is not the cause of AIDS.

   The below information was taken from the NIAID Fact Sheet
   "The Evidence That HIV Causes AIDS"
   National Institute of Allergy and Infectious Diseases
   National Institutes of Health

   Definition of AIDS

   The Centers for Disease Control (CDC) currently defines AIDS in an
adult or adolescent age 13 years or older as the presence of one of 26
conditions indicative of severe immunosuppression associated with HIV
infection, such as Pneumocystis carinii pneumonia (PCP), a condition
extraordinarily rare in people without HIV infection. These conditions
are commonly referred to as 'opportunistic infections'. Most other
AIDS-defining conditions are also 'opportunistic infections' which
rarely cause harm in healthy individuals. A diagnosis of AIDS is also
given to HIV-infected individuals with a CD4+ T cell count less than
200 cells per cubic millimeter (mm3) of blood. In children younger
than 13 years, the definition of AIDS is similar to that in
adolescents and adults, except that lymphoid interstitial pneumonitis
and recurrent bacterial infections are included in the list of
AIDS-defining conditions.

   The designation "AIDS" is a surveillance tool. Surveillance
definitions of AIDS have proven useful epidemiologically to track and
quantify the recent epidemic of HIV-mediated immunosuppression and its
manifestations. However, AIDS represents only the end stage of a
continuous, progressive pathogenic process, beginning with primary
infection with HIV, continuing with a chronic phase that is usually
asymptomatic, and leading to progressively severe symptoms and,
ultimately, profound immunodeficiency and opportunistic infections and
cancers.

   Evidence That HIV Causes AIDS

   Before the appearance of HIV, AIDS-related diseases such as PCP,
Kaposi's Sarcoma (KS) and Mycobacterium avium complex (MAC) were rare
in developed countries; today, they are common in HIV-infected
individuals.

   Prior to the appearance of HIV, AIDS-related conditions such as
PCP, KS and disseminated infection with MAC were extraordinarily rare
in the United States. In a 1967 survey, only 107 cases of PCP in this
country had been described in the medical literature, virtually all
among individuals with underlying immunosuppressive conditions. Before
the AIDS epidemic, the annual incidence of Kaposi's sarcoma in the
United States was 0.2 to 0.6 per million population, and only 32
individuals with disseminated MAC disease had been described in the
medical literature.

   By the end of 1999, CDC had received reports of 166,368
HIV-infected patients in the United States with definitive diagnoses
of PCP, 46,684 with definite diagnoses of KS, and 41,873 with
definitive diagnoses of disseminated MAC.

   AIDS and HIV infection are invariably linked in time, place and
population group.

   Historically, the occurrence of AIDS in human populations has
closely followed the appearance of HIV. In the United States, the
first cases of AIDS were reported in 1981 among homosexual men in New
York and California and retrospective examination of frozen blood
samples from a cohort of gay men showed the presence of HIV antibodies
as early as 1978 but not before then. Subsequently, in every country
and city where AIDS has appeared, evidence of HIV infection has
preceded AIDS by just a few years.

   Many studies agree that only a single factor, HIV, predicts
whether a person will develop AIDS.

   Other viral infections, bacterial infections, sexual behavior
patterns and drug abuse patterns do not predict who develops AIDS.
Individuals from diverse backgrounds, including heterosexual men and
women, homosexual men and women, hemophiliacs, sexual partners of
hemophiliacs and transfusion recipients, injection-drug users and
infants have all developed AIDS, with the only common denominator
being their infection with HIV.

   Numerous serosurveys show that AIDS is common in populations where
many individuals have HIV antibodies. Conversely, in populations with
low seroprevalence of HIV antibodies, AIDS is extremely rare.

   Foe example, in the southern African country of Zimbabwe
(population 11.4 million), more than 25 percent of adults ages 15 to
49 are estimated to be HIV-positive, based on numerous studies. As of
November 1999, 74, 000 cases of AIDS were reported to the World Health
Organization (WHO). In contrast, Madagascar, an island country off the
southeast coast of Africa (population 15.1 million) with a very low
seroprevalence rate, reported only 37 cases of AIDS to WHO through
November 1999.

   In cohort studies, severe immunosuppression and AIDS-defining
illnesses occur exclusively in individuals who are HIV-infected.

   Conversely, matched controls, individuals with similar lifestyles
but without HIV infection, virtually never suffer these symptoms.

   For example, in one cohort in Vancouver, investigators followed
715 homosexual men for a median of 8.6 years. Every case of AIDS in
this cohort occurred in individuals who were positive for HIV
antibodies. No AIDS-defining illnesses occurred in men who remained
negative for HIV antibodies, despite the fact that these men had
appreciable patterns of illicit drug use and receptive anal
intercourse.

   In some studies conducted, it has been shown that death rates are
markedly higher among HIV-seropositive individuals than among
HIV-seronegative individuals.

   Excess mortality among HIV-seropositive people also has been
repeatedly observed in studies in developed countries, perhaps most
dramatically among hemophiliacs. For example, 6,278 hemophiliacs where
studied in the United Kingdom during the period 1977-91. Among 2,448
with severe hemophilia, the annual death rate was stable at 8 per
1,000 during 1977-84. While deaths rates remained stable at 8 per
1,000 from 1985-92 among HIV-negative persons with severe hemophilia,
deaths rose steeply among those who had become HIV-positive following
HIV-tainted transfusions during 1979-1986, reaching 81 per 1,000.

   The specific immunologic profile that typifies AIDS—a persistently
low CD4+ T cell count—is extraordinarily rare in the absence of HIV
infection or other known cause of immunosuppression.

   For example, in the MACS study, 22,643 CD4+ T-cell counts were
carried out, related to 2,713 HIV-negative men. There was only one
individual with a CD4 + T-cell count persistently lower than 300
cells/mm3. This individual was taking other drugs that would have had
an affect on his CD4 count.

   Nearly everone with AIDS has antibodies to HIV.

   A survey of 230,179 AIDS patients in the United States revealed
only 299 HIV-seronegative individuals. An evaluation of 172 of these
299 patients found 131 actually to be seropositive; an additional 34
died before their serostatus could be confirmed.

   HIV can be detected in virtually everyone with AIDS.

   Recently developed sensitive testing methods, including the
polymerase chain reaction (PCR) and improved culture techniques, have
enabled researchers to find HIV in patients with AIDS with few
exceptions. HIV has been repeatedly isolated from the blood, semen and
vaginal secretions of patients with AIDS, findings consistent with the
epidemiologic data demonstrating AIDS transmission via sexual activity
and contact with infected blood.

   The HIV-infected twin develops AIDS while the uninfected twin does
not.

   Researchers have documented cases of HIV-infected mothers who have
given birth to twins, one of whom is HIV-infected and the other not.
The HIV-infected children developed AIDS, while the other children
remained clinically and immunologically normal.

   Studies of transfusion-acquired AIDS cases have repeatedly led to
the discovery of HIV in the patient as well as in the blood donor.

   Numerous studies have shown an almost perfect correlation between
the occurrence of AIDS in a blood recipient and donor, and evidence of
similar HIV strains in both the recipient and the donor.

   HIV causes the death of CD4+ T lymphocytes in vitro and in vivo.

   CD4+ T cells are the cells depleted in people with AIDS. Although
the loss of CD4+ T cells is not the only immune defect seen in people
with AIDS, the observation that HIV also infects and damages these
cells in vitro establishes an obvious link between HIV and AIDS.

   Among HIV-infected patients who receive anti-HIV therapy, those
whose viral loads are driven to low levels are much less likely to
develop AIDS or die than patients who do not respond to therapy. Such
an effect would not be seen if HIV did not have a central role in
causing AIDS.

   Clinical trials in both HIV-infected children and adults have
demonstrated a link between a good virologic response to therapy i.e.
a reduced risk of developing AIDS or dying.

   This effect has also been seen in routine clinical practice. For
example, in an analysis of 2,674 HIV-infected patients who started
highly active antiretroviral therapy (HAART) in 1995-1998, 6.6 percent
of patients who achieved and maintained undetectable viral loads
developed AIDS or died within 30 months, compared with 20.1 percent of
patients who never achieved undetectable concentrations.

   HIV fulfills Koch's postulates as the cause of AIDS

   Koch's postulates of disease causation stipulate: 1) the suspected
cause must be strongly associated with the disease, 2) the suspected
agent can be isolated and propagated outside the host, and 3) that the
transfer of the agent to an uninfected host, man or animal, produces
the disease in that host.

   With regard to postulate 1), numerous studies from around the
world show that virtually all AIDS patients are HIV-seropositive: that
is they carry antibodies that indicate HIV-infection. With regard to
postulate 2), modern techniques have allowed the isolation of HIV in
virtually all AIDS patients, as well as in almost all HIV seropositive
individuals with both early-and late-stage disease. Postulate 3) has
been fulfilled in incidents involving three laboratory workers with no
other risk factors who developed AIDS or severe immunosuppression
after accidental exposure to concentrated, cloned HIV in the
laboratory. In all three cases, HIV was isolated from the infected
individual, sequenced and shown to be the infecting strain of virus.

   In addition, through December 1999, the CDC had received reports
of 56 health care workers in the United States with documented,
occupationally acquired infection, of whom 25 have developed AIDS in
the absence of other risk factors. The development of AIDS following
known HIV seroconversion has also been repeatedly observed in
pediatric and adult blood transfusion cases, in mother-to-child
transmission, and in studies of hemophilia, injecting drug use and
sexual transmission in which seroconversion can be documented using
serial blood samples.

   Answering the skeptics, responses to arguments that HIV does not
cause AIDS

   Myth: HIV antibody testing is unreliable
   Fact: Diagnosis of infection using antibody testing is one of the
best-established concepts in medicine. HIV antibody tests exceed the
performance of most other infectious disease tests in both sensitivity
(the ability of the screening test to give a positive finding when the
person tested truly has the disease) and specificity (the ability of
the test to give a negative finding when the subjects tested are free
of the disease under study). Current HIV antibody tests have
sensitivity and specificity in excess of 98% and are therefore
extremely reliable.

   Progress in testing methodology has also enabled detection of
viral genetic material, antigens and the virus itself in body fluids
and cells. While not widely used for routine testing due to high cost
and requirements in laboratory equipment, these direct testing
techniques have confirmed the validity of the antibody tests.

   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 Tuberculosis
(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.

   For example, in a study in Cote d'Ivoire, HIV-seropositive
individuals with pulmonary tuberculosis (TB) were 17 times more likely
to die within six months than HIV-seronegative individuals with
pulmonary TB. In Malawi, mortality over three years among children who
had received recommended childhood immunizations and who survived the
first year of life was 9.5 times higher among HIV-seropositive
children than among HIV-seronegative children. The leading causes of
death were wasting syndrome and respiratory conditions. Elsewhere in
Africa, findings are similar.

   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 M. tuberculosis is not the cause of
tuberculosis or that hepatitis B virus is not a cause of liver
disease.

   Myth: AZT and other antiretroviral drugs, not HIV, cause AIDS.
   Fact: The vast majority of people with AIDS never received
antiretroviral drugs, including those in developed countries prior to
the licensure of AZT in 1987, and people in developing countries today
where very few individuals have access to these medications. As with
medications for any serious diseases, antiretroviral drugs can have
toxic side effects. However, there is no evidence that antiretroviral
drugs cause the severe immunosuppression that typifies AIDS, and
abundant evidence that antiretroviral therapy, when used according to
the established guidelines, can improve the length and quality of life
of HIV-infected individuals.

   In the 1980s, clinical trials enrolling patients with AIDS found
that AZT given as single-drug therapy conferred a modest (and
short-lived) survival advantage compared to placebo. Among
HIV-infected patients who had not yet developed AIDS,
placebo-controlled trials found that AZT given as single-drug therapy
delayed, for a year or two, the onset of AIDS-related illness.
Significantly, long-term follow-up of these trails did not show a
prolonged benefit of AZT, but also never indicated that the drug
increased disease progression or mortality. The lack of excess AIDS
cases and death in the AZT arms of these placebo-controlled trials
effectively counters the argument that AZT causes AIDS.

   Subsequent clinical trials found that patients receiving two-drug
combinations had up to 50 percent increases in time to progression to
AIDS and in survival when compared to people receiving single-drug
therapy. In more recent years, three-drug combination therapies have
produced another 50 percent to 80 percent improvements in progression
to AIDS and in survival when compared to two-drug regimens in clinical
trials. Use of potent anti-HIV combination therapies has contributed
to dramatic reductions in the incidence of AIDS and AIDS-related
deaths in populations where these drugs are widely available, an
effect which clearly would not be seen if antiretroviral drugs caused
AIDS.

   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 the United States 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: 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 111 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: High usage of clotting factor, not HIV, leads to CD4+ T-cell
reduction 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 only a small proportion of
AIDS cases are among 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. The CDC estimates that 30 percent of
new HIV infections in the United States in 1998 were in women. As the
number of HIV-infected women has risen, so too has the number of
female AIDS patients in the U.S. In 1998, approximately 23% of
adult/adolescent AIDS cases in the United States were among women. In
the same year, AIDS was the fifth leading cause of death among women
aged 25 to 44 in the U.S.

   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
(shingles) 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. Although the fraction
of CD4+ T cells that is infected with HIV at any given time is never
extremely high (only a small subset of activated cells serve as ideal
targets of infection), several groups have shown that rapid cycles of
death of infected cells and infection of new target cells occur
throughout the course of disease.

   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: 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 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.