Proc. Natl. Acad. Sci. USA
Vol.86, pp. 755-764, February 1989
Human Immunodeficiency virus and acquired immunodeficiency
syndrome: Correlation but not causation*
PETER H. DUESBERG
Department of Molecular Biology, Stanley Hall, University
of California, Berkeley, CA 94720
Contributed by Peter H. Duesberg, June 14, 1988; revision
received October 21, 1988
ABSTRACT AIDS is an acquired immunodeficiency syndrome defined by
a severe depletion of T cells and over 20 conventional degenerative and
neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with
risk factors, such as about 8 years of promiscuous male homosexuality,
intravenous drug use, or hemophilia. Since AIDS also correlates with antibody
to a retrovirus, confirmed in about 40% of American cases, it has been
hypothesized that this virus causes AIDS by killing T cells. Consequently,
the virus was termed human immunodeficiency virus (HIV), and antibody to
HIV became part of the definition of AIDS. The hypothesis that HIV causes
AIDS is examined in terms of Koch's postulates and epi- demiological, biochemical,
genetic, and evolutionary conditions of viral pathology. HIV does not fulfill
Koch's postulates: (i) free virus is not detectable in most cases of AIDS;
(ii) virus can only be isolated by reactivating virus in vitro from a few
latently infected lymphocytes among millions of uninfected ones; (iii)
pure HIV does not cause AIDS upon experimental infection of chimpanzees
or accidental infection of health humans. Further, HIV violates classical
conditions of viral pathology. (i) Epidemiological surveys indicate that
the annual incidence of AIDS among antibody-positive persons varies from
nearly 0 to over 10%, depending critically on nonviral risk factors. (ii)
HIV is expressed in <_1 of every 10 [4th power] T cells it supposedly
kills in AIDS, whereas about 5% of all T cells are regenerated during the
2 days it takes the virus to infect a cell. (iii) If HIV were the cause
of AIDS, it would be the first virus to cause a disease only after the
onset of antiviral immunity, as detected by a positive "AIDS test."
(iv) AIDS follows the onset of antiviral immunity only after long and unpredictable
asymptomatic intervals averaging 8 years, although HIV replicates within
1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly
causes AIDS by killing T cells, although retroviruses can only replicate
in viable cells. In fact, infected T cells grown in culture continue to
divide. (vi) HIV is isogenic with all other retroviruses and does not express
a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have
a paradoxical, country-specific pathology, causing over 90% pneumocystis
pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever,
and diarrhea in Africa. (viii) It is highly improbable that within the
last few years two viruses (HIV-1 and HIV-2) that are only 40% sequence-related
would have evolved that could both cause the newly defined syndrome AIDS.
Also, viruses are improbable that kill their only natural host with efficiencies
of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient
for AIDS and that it may not even be necessary for AIDS because its activity
is just as low in symptomatic carriers as in asymptomatic carriers. The
correlation between antibody to HIV and AIDS does not prove causation,
because otherwise indistinguishable diseases are now set apart only on
the basis of this antibody. I propose that AIDS is not a contagious syndrome
caused by one conventional virus or microbe. No such virus or microbe would
require almost a decade to cause primary disease, nor could it cause the
diverse collection of AIDS diseases. Neither would its host range be as
selective as that of AIDS, nor could it survive if it were as inefficiently
transmitted as AIDS. Since AIDS is defined by new combinations of conventional
diseases, it may be caused by new combinations of conventional pathogens,
including acute viral or microbial infections and chronic drug use and
malnutrition. The long and unpredictable intervals between infection with
HIV and AIDS would then reflect the thresholds for these pathogenic factors
to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis.
The important thing is not to stop questioning.
In 1981, acquired immunodeficiency was proposed to be the common denominator
of a newly defined syndrome (AIDS) of diseases that were on the rise in
promiscuous male homosexuals and intravenous drug users, referred to as
"AIDS risk groups" (1,2). Since then, about 70,000 persons have
developed AIDS in the U.S., of whom over 90% are still from these same
risk groups (3,4). The hallmark of AIDS is a severe depletion of T cells
(3, 5-7). By definition, this immunodeficiency manifests itself in over
20 previously known degenerative and neoplastic diseases, including Kaposi
sarcoma, Burkitt and other lymphomas, Pneumocystis pneu- monia, diarrhea,
dementia, candidiasis, tuberculosis, lymphadenopathy, slim disease, fever,
herpes, and many others (5, 7-11). The frequent reference to AIDS as a
new disease (12-14), instead of a new syndrome composed of old diseases,
has inspired a search for a single new pathogen (12). However, it is debatable
whether a single pathogen can explain over 20 diseases, whether a clustering
of old diseases in risk groups that only recently became visible signals
a new pathogen, and whether an AIDS pathogen must be infectious. Indeed,
compared to conventional infectious diseases, AIDS is very difficult to
acquire and has a very selective host range, usually manifesting only in
individuals who have taken AIDS risks for an average of 8 years (see below).
The Virus-AIDS Hypothesis.
About 40% of the AIDS patients in the U.S. (5), and many of those who
are at risk for AIDS, have been confirmed to have neutralizing antibodies
to a retrovirus (3, 7) that was discovered in 1983 (15). These antibodies
are detected by the "AIDS test" (3). Less than a year later,
in 1984, this virus was adopted as the cause of AIDS by the U.S. Department
of Health and Human Services and the AIDS test was registered as a patent,
even before the first American study on the virus was published (16). The
epidemiological correlation between these antibodies and AIDS is the primary
basis for the hypothesis that AIDS is caused by this virus (3, 7, 12, 14,
17, 18). AIDS is also believed to be caused by this virus because AIDS
diseases appear in a small percentage (see below) of recipients of blood
transfusions that have antibo- dies to this virus (3, 12, 19-22). In view
of this the virus has been named human immunodeficiency virus (HIV) by
an international committee of retrovirologists (18) and antibody to HIV
became part of the definition of AIDS (3, 5, 7). If confirmed, HIV would
be the first clinically relevant retrovirus since the Virus-Cancer Program
called for viral carcinogens in 1971 (23, 24).
The virus-AIDS hypothesis holds that the retrovirus HIV causes AIDS
by killing T cells in the manner of a cytocidal virus (3, 6, 7, 12, 18)
and is transmitted by sex and parenteral exposure (3, 7, 12, 19, 22). Early
evidence for a T-cell-specific HIV receptor lent support to this hypothesis
(25). Recently, however, the presumed T-cell specificity of HIV has lost
ground, as HIV is only barely detectable in T cells and often is detectable
only in monocytes (26-28) and other body cells (23, 29-32), displaying
the same lack of virulence and broad host range toward differentiated cells
as all other human and animal retroviruses (17, 23). In about 50% of those
who habitually practice risk behavior or regularly receive transfusions,
AIDS is estimated to occur after an average asymptomatic period of about
8 years from the onset of antiviral immunity, and in up to 100% after about
15 years (5-7, 20-22, 33-38). Therefore, HIV is called a "slow"
virus, or lentivirus (40). It is on the basis of the relatively high conversion
rates of these risk groups that every asymptomatic infection by HIV is
now being called "HIV disease" (7), and that some are subjected
to chemotherapy (39). Nevertheless, individual asymptomatic periods are
unpredictable, ranging from <1 to >15 years (22, 33-38). Once AIDS
is diagnosed, the mean life expectancy is about 1 year (35).
The early adoption of the virus-AIDS hypothesis by the U.S. Department
of Health and Human Services (16) and by the retrovirologists (17, 18)
is the probable reason that the hypothesis was generally accepted without
scrutiny. For instance, the virus is typically referred to as deadly by
the popular press (41, 42) and public enemy number 1 by the U.S. Department
of Health and Human Services (43). In view of this, it is surprising that
the virus has yet to cause the first AIDS case among hundreds of unvaccinated
scientists who have propagated it for the past 5 years at titers that exceed
those in AIDS patients by up to 6 orders of magnitude (see below) with
no more containment than is required for marginally pathogenic animal viruses
(44). It is also surprising that despite 2000 recorded (and probably many
more unrecorded) parenteral exposures to HIV-infected materials, unvaccinated
health care workers have exactly the same incidence of AIDS as the rest
of the U.S. labor force (19, 22, 45, 186). Further, it is difficult to
believe that a sexually transmitted virus (7, 12) would not have caused
more than 1649 sex-linked AIDS cases among the 125 million American women
in 8 years (4) -- and this number is not even corrected for the antibody-negative
women who might have developed such diseases over an 8-year period. Moreover,
it is paradoxical for a supposedly new viral epidemic (12-14) that the
estimates of infected persons in the U.S. have remained constant at 0.5
to 1.5 million (46, 47) or even declined to <1 million (7, 38) since
the "AIDS test" became available in 1985.
About 2 years ago I proposed that HIV is not likely to be the cause
of AIDS (23, 48-50, 180). This proposal has since been fiercely challenged
or defended at meetings and in publications (14, 32, 51-65, 180). Here
I respond to these challenges.
HIV Does Not Meet Koch's Postulates
HIV Cannot Account for the Loss of T Cells and the Clinical Course
The causative agent of an infectious disease is classically defined
by the postulates of Robert Koch and Jacob Henle (66, 67). They were originally
formulated a priori by Henle about 50 years before bacteria and viruses
were discovered to be pathogens(67). However, their definitive text was
formulated by Koch to distinguish causative from other bacteria at a time
when bacteriologists applying newly developed tools in the search for pathogenic
microbes found all sorts of bacteria in humans. This situation was quite
similar to our current increasing proficiency in demonstrating viruses
(68). The first of these postulates states that "the parasite must
be present in every single case of the disease, under conditions that can
account for the pathological lesions and the clinical course of the disease"
(67). However, there is no free virus in most -- and very little in some
-- persons with AIDS, or in asymptomatic carriers (69, 70). Virus titers
range from 0 to 10 infectious units per milliliter of blood (69, 70). Viral
RNA is found in a very low percentage (see below) of blood cells of 50-80%
of antibody-positive persons (71-74, 187). Further, no provirus is detectable
in blood cells of 70-100% of symptomatic or asymptomatic antibody-positive
persons, if tested by direct hybridization of cellular DNA with cloned
proviral DNA (73, 75, 187) at the limit of detection by this method (76).
Antibody to HIV is confirmed in only about 40% of the U.S. cases and in
only 7% of the AIDS cases from New York and San Francisco, which represent
one-third of all U.S. cases (5). In some cases, even the antibody to HIV
disappears, due to chronic dormancy or loss of the HIV provirus (77, 78)
-- analogous to the loss of antibody to other viruses long after infection.
Indeed, the Centers for Disease Control publishes specific guidelines for
AIDS cases in which laboratory evidence for HIV is totally negative (5).
Thus, although viral elements can be traced in many AIDS patients, and
antibody to HIV is, at least by definition, present in all of them, HIV
violates Koch's first postulate in terms of a tangible presence, of being
"under conditions that can account for" the loss of T cells,
and of the "clinical course of the disease" that lags 8 years
The absence of free virus in most AIDS cases and in antibody-positive
asymptomatic carriers explains why HIV is not casually transmitted (19,
22, 23, 35). For example, the probability of transmission of the virus
from an antibody-positive to an antibody-negative person by heterosexual
intercourse is estimated to be 1 in 500 (79, 80).
Due to Extremely Low Titers, HIV Can Be Isolated Only with Great
Difficulty from AIDS patients.
Koch further postulated that it must be possible to isolate and propagate
the etiological agent from all cases of the disease. However, virus isolation,
although possible in up to 80% of AIDS cases, is technically very difficult
and is perhaps best described as maieutic (23, 69, 70, 81-84). It depends
on reactivation of dormant proviruses from one or a few latently infected
lymphocytes among millions of uninfected lymphocytes from AIDS patients.
This is only possible by culturing these cells for several weeks in vitro,
away from the suppressive, virus-neutralizing immune system of the host
(23, 48-50). Even then success sometimes comes only after 15 (!) trials
(85). These difficulties and the often over 20% failure rate (84) in isolation
of HIV from AIDS patients are consistent with the extremely low titers
of HIV in such patients. Thus, HIV does not meet Koch's second postulate.
In vitro reactivation of latent HIV from antibody-positive persons is
exactly analogous to the in vitro reactivation of latent Epstein-Barr virus
(EBV) from healthy persons with antibody to EBV (86). As in the case of
HIV (see below), acute EBV infections occasionally cause mononucleosis
(86-88). Subsequent antiviral immunity restricts EBV to chronic latency
(86). Since latent EBV, again like latent HIV, is present in only 1 of
10 [7th power] lymphocytes, millions of these cells must be cul- tivated
in vitro to reactivate the virus (86).
HIV Does Not Reproduce AIDS When Innoculated into Animals or Humans.
Animal Infections. Koch's third postulate calls for inducing the disease
by experimental infection of a suitable hosts with pure pathogen. Chimpanzees
infected with pure HIV develop antibodies, indicating that they are susceptible
to HIV. However, all attempts to cause AIDS in chimpanzees have been unsuccessful,
even after they have been antibody-positive for 4 to 5 years (23). Thus,
Koch's third postulate has not been fulfilled in animals.
Accidental human infections. Due to the extremely low titers of HIV
in all antibody-positive materials, very few infections have occurred.
Four women who received infected donor semen in 1984 developed antibody
to HIV. Yet none of them developed AIDS or transmitted the virus to their
husbands, although insufficient time has elapsed for the average latent
period that the virus is thought to require to cause AIDS (see below).
Moreover, three of these women subsequently became pregnant and gave birth
to healthy infants (89). Further, 15 to 20 accidental infections of health
care workers and scientists propagating HIV were identified during the
last 4 years on the basis of antiviral antibodies, and none of these people
have developed AIDS (19, 22, 23, 45, 85, 90, 186).
Recently, a single conversion to AIDS of such an antibody-positive health
care worker was reported anonymously without data on gender, latent period,
or AIDS symptoms (45). This case was claimed to prove Koch's third postulate
(14). However, 2586 health care workers got AIDS without occupational infection.
About 95% of these fall into the conventional risk groups and 5% are without
verifiable AIDS risks (4,45) -- which are notoriously difficult to verify
(91, 92). From the 135 (5% of 2586) health care workers who developed AIDS
without verifiable risks, the one who contracted an occupational infection
was selected to prove that such infections, rather than other risks, caused
AIDS. It is arbitrary to base a hypothesis on 1 case when 134 cases do
not support the hypothesis. To prove the hypothesis, it is necessary to
show that the percentage of health care workers with AIDS who do not belong
to the known risk groups exceeds that of the rest of the population and
reflects their sexual distribution. However, the incidence and even the
sexual distribution of AIDS cases among health care workers are exactly
the same as that of AIDS in the general population (4), namely 92% males,
although 75% of the health care workers are female (45). Moreover, a subsequent
study (186) that included this case described only transient, mononucleosis-like
symptoms but not one AIDS case among occupationally infected health care
Blood transfusions are another source of iatrogenic infections. The
best-documented cases are the 10,000 to 14,000 U.S. hemophiliacs with antibody
to HIV (19, 38, 47, 93, 94), of whom only 646 developed symptoms of AIDS
between 1981 and August 1988 (4). During the year that ended in August
1988, 290 developed AIDS, whereas 178 developed AIDS in the previous year
(4). This corresponds to annual conversion rates of about 1-3%. Higher
rates, of up to 25%, have been observed in certain groups of hemophiliacs
(20, 21, 35, 36, 38). However, the view that AIDS in recipients of transfusions
is due to HIV transmission is
presumptive on several grounds. (i) Blood transfusion does not distinguish
between HIV and other undetected viruses, microbes, and blood-borne toxins.
This is particularly true since HIV-positive blood was never knowingly
transfused. (ii) It is presumed that the recipients had no AIDS risks other
than HIV during the average of 8 years between HIV infection and AIDS symptoms
(20, 21). The transfusion evidence would be more convincing if AIDS appeared
in step with virus replication (see below) soon after a singular transfusion.
(iii) Transfusion-related AIDS cases occur primarily in persons with other
health risks, such as hemophilia, that are not representative of healthy
individuals. (iv) Above all, the transfusion cases are all anecdotal (95,
96). There are no controlled studies to show that recipients of transfusions
with antibody to HIV have more of the diseases now called AIDS than those
without antibody to HIV.
The assertion that HIV causes AIDS is also contained in the erroneous
claims that new cases of transfusion AIDS have virtually ceased appearing
since the AIDS test became available in 1985 (12, 14), due to a factor-of-40
reduction of transfusions with antibody-positive blood (95). In fact, adult
transfusion AIDS cases have doubled and pediatric cases have tripled in
the year ending August 8, compared to the previous year (4, 49). The increase
in adult cases could be expected if one were to accept the assumptions
that HIV requires 8 years to cause AIDS (see below) and that there was
a rapid increase in unconfirmed HIV transfusions 8 years ago, which stopped
3 years ago. However, the increase in pediatric cases in the face of a
40-fold reduction of antibody-positive transfusions argues directly against
HIV as the cause of AIDS, because the average latent period in children
is only 2 years (21, 36).
HIV Does Not Meet Established Epidemiological, Biochemical, Genetic,
and Evolutionary Criteria of a Viral Pathogen
Epidemiologies of AIDS and HIV Are Not Consistent.
Epidemiology has been proposed as adequate to identify causative agents,
particularly in human diseases where Koch's postulates are difficult to
meet (67), as in the case of HIV (12, 14, 32). Nevertheless, even a consistent
correlation with virus -- not with antibody -- would fulfill only the first
postulate. However, the epidemiologies of AIDS and HIV are not consistent
in different risk groups and countries.
About 10% of the 30 million people in Zaire have been reported since
1985 to be antibody-positive (46, 98, 184). How- ever, only 335 AIDS cases
have been reported in Zaire as of 1988 (97, 99). This corresponds to an
annual conversion rate of 0.004%. Also, since 1985, 6% of the 6 million
Haitians have been reported to be antibody-positive (46, 100), but only
912 had developed AIDS by 1988 (97). This corresponds to an annual conversion
rate of 0.1%. Of 0.5 to 1.5 million antibody-positive Americans, about
29,000 (including 9,000 who meet only the 1987 definition for AIDS (5))
developed AIDS in the year ending August 1988, and, according to earlier
definitions, 16,000 to 17,000 developed AIDS in each of the previous 2
years (4). This corresponds to an annual conversion rate of about 1.5%
for the average antibody-positive American. Thus, the AIDS risk of an antibody-positive
person varies with the country of residence. These calculations all assume
that the pools of short- and long-term HIV carriers in each of these countries
are comparable. This assumption is based on the claims that HIV was newly
introduced into all countries with AIDS about 10 to 20 years ago (3, 7,
Moreover, the AIDS risk of an antibody-positive American varies a great
deal with his or her risk group. For example, 3-25% of antibody-positive
Americans who habitually practice risk behavior or are hemophiliacs develop
AIDS annually (7, 21, 22, 33-38). Thus, the 1.5% annual conversion rate
of antibody-positive Americans is an average of minorities with high conversion
rates of 3-25% and a majority with a conversion rate close to 0%.
Since the incidence of AIDS among antibody-positive persons varies from
0 to over 10% depending on factors defined by lifestyle, health, and country
of residence (35), it follows that HIV is not sufficient to cause AIDS.
AIDS Occurs Despite Minimal Viral Activity.
During replication, viruses are biochemically very active in the host
cell. If they replicate in more cells than the host can spare or regenerate,
they typically cause a disease (48, 86).
Paradoxically, HIV is very inactive even when it is said to cause fatal
immunodeficiency. Viral RNA synthesis is detectable in only 1 of 10 [4th
power] to 10 [6th power] mononuclear lymphocytes, including T cells (71-74).
Frequently, virus can only be found in monocytes, and not in T cells (26-28).
Virus expression recorded in monocyte-macrophages is at the same low levels
as in other lymphocytes (72). Thus, there is as yet no experimental proof
for the suggestion, based on experiments in cell culture, that monocyte-macrophages
may be the reservoirs of the virus in vivo (6, 12, 28). Also, very few
lung and brain cells ever express HIV (101, 102, 187). At this level of
infiltration HIV cannot account by any known mechanism for the loss of
T cells that is the hallmark of AIDS (3, 5, 6, 12), even if all actively
infected T cells died. During the 2 days it takes for a retrovirus to replicate,
the body regenerates about 5% of T cells (23, 103), more than enough to
compensate for presumptive losses due to the virus. Hence, HIV cannot be
sufficient to cause AIDS.
Although there is virtually no free virus, and HIV RNA synthesis is
extremely low, both in AIDS patients and in asymptomatic carriers (71-74),
it has been argued that the viral core protein p24 is produced at higher
levels in AIDS patients than in asymptomatic carriers (83, 84, 104-108,
183). However, all studies on p24 report AIDS cases that occur without
p24 antigenemia, indicating that p24 is not necessary for AIDS (83, 84,
104-108, 183). They also report antigenemia without AIDS, indicating that
p24 is not sufficient for AIDS (72, 84, 104-108, 183). Moreover, antigenemic
carriers are not viremic because they always maintain an excess of virus-neutralizing
antibodies directed against the viral envelope, a positive AIDS test (72,
83, 84, 104-108, 183). In addition, the colorimetric antibody test used
to measure p24 protein raises unresolved questions. Reportedly, the assay's
detection limit is 50 pg/ml, and up to 100 times more p24 than that is
found in some HIV carriers (83, 84, 104-109). Five hundred picograms of
p24 is the protein equivalent of 10 [6th power] HIV particles, given 10
[-3rd power] pg per retrovirus, half of which is core protein (110). Yet
such high concentrations of p24 cannot be reconciled with the extremely
low numbers of cells in AIDS patients that are engaged in viral RNA synthesis
(6, 71-74, 101, 102), nor can the failure to isolate virus from 20-50%
of p24-antigenemic patients (83, 84). Based on my 24-year experience with
retroviruses, only large numbers of infected cells growing in the absence
of antiviral immunity in vivo or in vitro produce such high titers of virus
or viral protein. Thus, the assertions that HIV becomes activated during
AIDS or that p24 antigenemia is necessary for the syndrome (6, 7, 12, 31,
35) are without experimental support.
AIDS Occurs Despite Antiviral Immunity.
Viruses typically cause disease before virus-neutralizing antibodies
and cellular immunity appear. Antiviral antibodies signal a successful
rejection of the virus and a lasting protection (vaccination) against diseases
by the same or related viruses. Immunity is the only weapon against viral
Paradoxically, HIV is said to cause AIDS, by definition, only years
after inducing very active antiviral immunity (3, 5). If this assertion
were correct, HIV would be the first disease
to cause a disease only after antiviral immunity. Yet the effectiveness
of this immunity is the reason that provirus remains dormant and that free
HIV cannot be found in AIDS patients (69). In view of this, vaccination
of antibody-positive persons would appear to be completely superfluous,
even if HIV were the cause of AIDS (3, 7, 12, 111-113). The claims of some
scientists that antiviral antibodies fail to neutralize HIV (3, 32, 55,
56, 59, 113-115) are incompatible with the efficient immunity in vivo and
with experimental evidence for virus-neutralizing activity in vitro (23,
Although most viruses are eliminated by immunity, some, such as the
retroviruses and the herpesviruses, may persist -- severely restricted
by antiviral immunity -- as latent infections (23, 86, 87). Such viruses
can again become pathogenic, but only when they are reactivated. For example,
upon reactivation,, the herpesviruses cause fever blisters or zoster even
in the presence of serum antibody (120). Reactivation may follow a decline
of cellular immunity in response to other parasitic infections, radiation,
or immunosuppressive therapy (23, 86). Further, it has been claimed that
8 years after primary infection and immunity, latent measles virus may
cause subacute sclerosing panencephalitis (121) in about 1 case per million
(86) and that another latent paramyxovirus may cause multiple sclerosis
(121). However, these viruses could be isolated from each system in only
2 of 8 cases after cultivating millions of patient cells in vitro (121).
Moreover, multiple sclerosis has since been suggested to be caused by a
latent retrovirus closely related to HIV (122) and subacute encephalitis
by HIV (28, 187). Thus, there is no proven precedent for the hypothesis
that HIV causes AIDS only years after the onset of antiviral immunity and
yet remains as inactive as it is in asymptomatic infections.
It has been proposed that pathogenic HIV mutants arise during the long
intervals between infection and AIDS and that these mutants might escape
antiviral immunity by losing specific epitopes (28, 31, 82, 90, 112, 113,
123, 124) or even by changing their host range from T cells to microphages
(44). However, there is no report of a mutant HIV present at high titer
in AIDS. Further, it is very unlikely that a mutant could escape an existing
immunity, because it would share most variable and, of necessity, all constant
determinants with the parent virus. Even though all retroviruses, including
HIV (125-128), mutate at a frequency of 1 in 10 [4th power] nucleotides
per replicative cycle, they have never been observed to escape an existing
antiviral immunity. It has also been proposed that HIV escapes immunity
by spreading via cell-to-cell transmission (28, 32, 115, 117, 129). However,
consistent with the syncytium-blocking function of natural antibodies (23,
115, 119), there is no spread of HIV in vivo.
Intervals of 2 to 15 Years Between Infection and AIDS Are Incompatible
with HIV Replication.
If cytocidal viruses or retroviruses cause disease, they do so within
1 to 2 months of infection (23, 86). By that time, the host's immune system
either eliminates the virus or restricts it to latency, or the virus overcomes
the immune system and kills the host. Indeed, clinicians have reported
that, in rare cases, HIV causes a disease like mononucleosis prior to immunity,
presumably due to an acute infection (23, 69, 130, 186). Since this disease
correlates with viral activity (69) and disappears within weeks as the
body develops antiviral immunity, it may reflect the true pathogenic potential
Considering that HIV replicates within 2 days in tissue culture and
induces antiviral immunity within 1 to 2 months (19, 23, 69, 130), the
inevitably long and seemingly unpredictable intervals, ranging from 1 to
15 years (20, 35, 37), between the onset of antiviral immunity and AIDS
are bizarre. The average latent period is reported to be 8 years in adults
(21, 33-38) and 2 years in children (21, 36). Indeed, at least 2 years
of immunity is required before AIDS appears in adults (7, 38). If one accepts
that 50-100% of antibody-positive Americans eventually develop AIDS (7,
20-22, 33-37), the average 1.5% annual conversion corresponds to grotesque
viral latent periods of 30 to 65 years. These intervals between HIV infection
and AIDS clearly indicate that HIV by itself is not sufficient to initiate
AIDS. Because all genes of HIV are expressed during the early immunogenic
phase of the infection, AIDS should occur at that time, rather than years
later when it is latent (23).
In an effort to rationalize the long intervals between infection and
AIDS, HIV has been classified as a slow virus, or lentivirus (40), a type
of retrovirus that is thought to cause disease only after long incubation
periods (129). Yet there are no "slow" viruses. Since viral nucleic
acids and proteins are synthesized by the cell, viruses must replicate
as fast or faster than cells (i.e., within hours or days) to survive (86,
Nevertheless, as pathogens, viruses may be (i) fast in acute infections
that involve many actively infected cells, (ii) slow in subacute infections
that involve moderate numbers of actively infected cells, or (iii) asymptomatic
and latent. Retroviruses provide examples of each different pathogenic
role. Acute infections with the "slow" Visna/Maedi retrovirus
of sheep, a lentivirus, rapidly cause pneumonia (131), and those with equine
anemia lentivirus cause fever and anemia within days or weeks of infection
(132). Such infections typically generate titers of 10 [4th power] to 10
[5th power] infectious units per milliliter or gram of tissue (132, 133).
The caprine arthritis-encephalitis lentivirus is also pathogenic within
2 months of inoculation (134). Acute infections with other retroviruses
also rapidly cause debilitating diseases or cancers (23). This includes
retrovirus infections that are now considered to be animal models of AIDS,
termed simian or feline AIDS (12, 23, 30, 111, 135). Unlike HIV in AIDS,
these viruses are all very active when they cause diseases, and the respective
diseases appear shortly after infection (23). In rare cases, when antiviral
immunity fails to restrict Visna/Maedi or other retroviruses, they persist
as subacute symptomatic infections (3, 86, 129, 133). Under these conditions,
Visna/Maedi virus causes a slow, progressive pulmonary disease (129, 133,
136) by chronically infecting a moderate number of cells that produce moderate
titers of 10 [2nd power] to 10 [5th power] virus particles per gram of
tissue (136). However, in over 99% of all Visna/Maedi or caprine arthritis-encephalitis
virus infections, and in most equine anemia virus infections, the retrovirus
is either eliminated or restricted to latency by immunity, and hence asymptomatic,
exactly like almost all other retroviruses in mice, chickens, cats, and
other animals (23). For instance, 30-50% of all healthy sheep in the U.S.,
Holland, and Germany have asymptomatic Visna/Maedi virus infections (129,
137, 138), and 80% of healthy goats in the U.S. have asymptomatic caprine
arthritis-encephalitis virus infections (133) in the presence of antiviral
Thus, the progressive diseases induced by active retroviruses depend
on relative tolerance to the virus due to rare native or acquired immunodeficiency
or congenital infection prior to immune competence. Since tolerance to
HIV that would result in active chronic infection has never been observed
and is certainly not to be expected for 50-100% of infections (the percentage
of infections said to develop into AIDS (ref. 7 and above)), the rare retrovirus
infections of animals that cause slow, progressive diseases are not models
for how HIV might cause AIDS. Indeed, not one acute retrovirus infection
has ever been described in humans (23).
The Paradox of How HIV, a Noncytocidal Retrovirus, Is To Cause the
Degenerative Disease AIDS.
Unlike cytocidal viruses, which replicate by killing cells, retroviruses
need viable cells for replication (139). During retroviral infection, proviral
DNA becomes the cellular gene as it is integrated into the DNA of the cell.
Such a mechanism is superfluous for a cytocidal virus. Virus reproduction
from then on is essentially gene expression in viable cells, often stimu-
lating hyperplastic growth (17, 23). Alternatively, retroviruses survive
as latent proviruses, like latent cellular genes. The very distinction
of not killing the host cell is the reason that scientists have for so
long considered retroviruses to be the most plausible viral carcinogens
(17, 23, 140).
Yet HIV, a retrovirus, is said to behave like a cytocidal virus, causing
AIDS by killing billions of T cells (3, 5, 6, 12, 31). This is said even
though some infected T-cell lines remain immortal (12, 23), and primary
umbilical-cord blood cells may continue to divide in culture while propagating
up to 10 [6th power] infectious units per milliliter (82), much more than
in AIDS patients. Also, there are no cytopathic changes or cell death in
cultures of HIV-infected monocytes and macrophages (28, 141-146) and B
cells (17, 23, 147). As is typical of retroviruses, HIV does not kill its
The cytocidal effects that are occasionally observed in HIV-infected
cultures (but as yet, never in humans) soon after infection do not break
this rule (23). These early effects result from fusions of HIV-infected
and uninfected cells that depend on virus isolates and cell culture conditions
(23, 82, 146, 147), and are completely inhibited by antiviral antibody
(23, 115, 119). They are not HIV-specific, because many animal and human
retroviruses show conditional, but never absolute, cytocidal effects in
cell culture (23). Thus, the fusion effect in culture might be relevant
for the mononucleosis observed in some patients soon after infection, when
free virus (but no fusion-inhibitory antibody) is present. However, the
effect can- not be irrelevant to AIDS because there is plenty of fusion-inhibitory
antibody and because the virus isolates from some patients fuse, and those
from others don't (23, 82, 146, 147). Thus, HIV is not sufficient to kill
even the few T cells it infects in AIDS.
HIV Is a Conventional Retrovirus, Without an AIDS Gene.
The virus-AIDS hypothesis proposes that HIV is an unorthodox retrovirus
(6, 12, 14, 31, 32) containing specific suppressor and activator genes
that control the 2- to 15-year intervals between infection and AIDS (12,
17, 188). However, the two known HIVs (see below) are profoundly conventional
retroviruses. They have the same genetic complexity of about 9150 nucleotides,
the same genetic structure, including the three major essential retrovirus
genes linked in the order gag-pol-env, the same mechanism of replication,
and the same mutation frequency (3, 7, 17, 90, 125, 126, 148) as all other
retroviruses (17, 127, 128, 149, 150). Humans carry between 50 and 100
such retroviruses in their germ line, mostly as latent proviruses (151).
The presumably specific genes of the HIVs (12, 188) are alternative reading
frames of essential genes shared by all retroviruses (3, 7, 12, 23, 90,
148). Their apparent novelty is more likely to reflect new techniques of
gene analysis than to represent HIV-specific retroviral functions. Indeed,
analogous genes have recently been found in other retroviruses, including
one bovine and at least three other human retroviruses that do not cause
AIDS (23, 152, 188). Because HIV and all other retroviruses are isogenic,
the newly discovered genes cannot be AIDS-specific. Moreover, it is unlikely
that these genes even control virus replication. In vivo, HIV lies chronically
dormant, although the presumed suppressor genes are not expressed. In vitro,
HIV is propagated at titers of about 10 [6th power] per ml in the same
human cells in which it is dormant in vivo, although the presumed suppressor
genes are highly expressed (23, 188). Therefore, I propose that antiviral
immunity rather than viral genes suppress HIV in vivo, as is the case with
essentially all retroviruses in wild animals (23). Further, I propose that
the multiplicity of AIDS diseases are caused by a multiplicity of risk
factors (see below), rather than by one or a few viral activator genes,
since viral gene expression in AIDS is just as low as in asymptomatic carriers.
Also, the extremely low genetic complexity of HIV can hardly be sufficient
to control the inevitably long times between infection and AIDS, and the
great diversity of AIDS diseases. Thus, there is neither biochemical nor
genetic evidence that HIV genes initiate or maintain AIDS.
The Paradoxes of an AIDS Virus with Country- and Risk-Specific Pathologies
and Host Ranges.
It is yet another paradox of the virus-AIDS hypothesis that HIV is said
to cause very different diseases in different risk groups and countries.
For example, in the U.S. over 90% of AIDS patients have Pneumocystis pneumonia
or Kaposi sarcoma. However, Kaposi sarcoma is found almost exclusively
in homosexuals (8, 191). By contrast, in Africa over 90% of the AIDS cases
are manifested by slim disease, fever, and diarrhea (9, 10, 64). Moreover,
it is paradoxical that the prevalence of Kaposi sarcoma among U.S. AIDS
cases has shifted down from 35% in 1983 (156) to 6% in 1988 (4) (see below
and refs. 190 and 191), and Pneumo-cystis pneumonia has shifted up from
42% to 64% (8), while the alleged cause, HIV, has remained the same.
One explanation of these facts is that HIV is not sufficient to cause
AIDS but depends critically on country- and risk-specific cofactors. However,
the simplest explanation proposes that HIV is a harmless, idle retrovirus
that is not the cause of AIDS.
In view of the claims that AIDS is a sexually transmitted viral syndrome
(3, 7, 12), it is surprising (47, 64, 65, 91, 92, 154, 155) that, in the
U.S., about 90% of all HIV carriers and AIDS patients are male (4, 7, 22,
38, 47). Even if one assumes that the virus was originally introduced into
the U.S. through homosexual men (7), this epidemiology is hard to reconcile
with the spread of a sexually transmitted virus 8 years later. In order
to survive, a virus must infect new hosts, which it does most readily when
it is at the highest titer (153). In the case of HIV, this would be before
antiviral immunity, or 1 to 2 months after infection (69). Thus, the 8
years of AIDS in the U.S. represent about 50 to 100 human passages of HIV,
enough time for the virus to equilibrate between the sexes. By contrast,
the uniform sexual distribution of HIV in Africa appears consistent with
a sexually transmissible virus, underscoring the paradox of the U.S. epidemiology,
particularly since the viruses (12) and the epidemics (12-14, 90, 113)
of both countries are thought to be equally new.
A solution of the paradox is that HIV is not new but is endemic in Africa
and, like most retroviruses (23), is transmitted perinatally rather than
sexually. Accordingly, 10% of healthy Zairians are antibody-positive (46,
98, 184), and not more than 30% of the Kaposi sarcoma patients in Africa
are infected with HIV (157, 158). Indeed, perinatal transmission between
mother and child occurs with an efficiency of 30-50% (7, 22, 39), while
sexual transmission is extremely inefficient (65, 79, 80, 154, 155). Since
the virus is not endemic in the U.S., it is transmitted more often by parenteral
exposures associated with risk behavior (see below) than perinatally.
Evolutionary Arguments Against AIDS Viruses.
It is now claimed that there are at least two new retroviruses capable
of causing AIDS, HIV-1 and HIV-2 (3, 7, 12-14), which differ about 60%
in their nucleic acid sequences (148). Both allegedly evolved only 20 to
<100 years ago (12). Since viruses, like cells, are the products of
gradual evolution, the proposition that, within a very short evolutionary
time, two different viruses capable of causing AIDS would have evolved
or crossed over from another species is highly improbable (56, 64, 159).
It is also improbable that viruses evolved that kill their only natural
host with efficiencies of 50-100% as is claimed for the HIVs (7, 33-38).
Conclusions and Perspectives
It is concluded that HIV is not sufficient to cause AIDS because HIV
meets neither Koch's postulates nor established epidemiological, biochemical,
genetic, and evolutionary criteria of a viral pathogen. Further, it is
concluded that HIV may not even be necessary for AIDS because there is
neither biochemical nor genetic evidence that it initiates or maintains
AIDS. HIV infiltration and activity are just as low in symptomatic carriers
as in asymptomatic carriers, and HIV lacks an AIDS gene. The association
between AIDS and antibody to HIV -- now part of the definition of AIDS
-- does not prove causation because otherwise indistinguishable diseases
are now set apart only on the basis of this antibody. According to this
view, HIV is an ordinary harmless retrovirus that, in rare acute infections,
may cause a mononucleosis-like disease before immunity.
Antibody to HIV Is a Surrogate Marker for Risk of AIDS.
Although HIV does not appear to cause AIDS, it may serve in the U.S.
and Europe as a surrogate marker for the risk of AIDS for the following
reasons. (i) In these countries, HIV is not widespread but is one of the
most specific occupational infections of persons at risk for AIDS (3, 7,
38, 47, 61, 94, 160). (ii) Since HIV is extremely difficult to transmit,
like all latent viruses, it would specifically identify those who habitually
receive transfusions or intravenous drugs or are promiscuous. Indeed, the
probability of being antibody-positive correlates directly with the frequency
of drug use (38, 47, 160), transfusions (94, 161), and male homosexual
activity (38, 160). (iii) Since HIV is not cytocidal, it persists as a
minimally active virus in a small number of cells, which will chronically
boost antiviral immunity to produce a positive AIDS test. Latent EBV, cytomegalovirus,
or other herpes-virus infections will likewise maintain a chronic immunity
(86, 120), although less specific for AIDS risk. By contrast, antibodies
against viruses and microbes, which cannot persist at subclinical levels,
tend to disappear after primary infection.
Epidemiology is Not Sufficient to Prove Etiology.
It has been argued that Koch's postulates can be abandoned as proof
for etiology in favor of epidemiological correlations (67, 68, 162), most
recently in the case of HIV (14, 32). How- ever, adherence to this epidemiological
concept (68, 162) as a substitute for biochemical and genetic proof of
etiology has resulted in some of the most spectacular misdiagnoses in virology.
(a) Based on epidemiological correlations, EBV was thought to be the cause
of Burkitt pneumonia -- until Burkitt lymphomas free of the virus were
discovered (163). (It is ironic that HIV is currently a proposed cause
of Burkitt lymphoma (5).) (b) Also on the basis of seroepidemiological
evidence, retroviruses were thought to cause human and bovine leukemias
after bizarre latent periods of up to 40 years in humans (164), until the
discovery of these viruses in billions of normal cells of millions of asymptomatic
carriers cast doubt on this hypothesis (23). It is scarcely surprising
that the particular T cell from which a rare clonal leukemia originated
was also infected. It is consistent with this view that these tumors are
clonal and not contagious, like virus-negative leukemias, and that the
presumably causative viruses are biochemically inactive in the human and
bovine leukemias (23). Instead of viruses, the only specific markers of
such tumors are clonal chromosomal abnormalities (23). (c) Likewise, slow
viruses have gained acceptance as causes for such diseases as kuru, Creutzfeld-Jacob
disease, and Alzheimer disease on the basis of epidemiological evidence
(165), although these viruses have never been detected.
Proof of Etiology Depends on Evidence for Activity.
Regrettably, the hasty acceptance of the virus as the cause of AIDS
(16), signaled by naming it HIV (18), has created an orthodoxy whose adherents
prefer to discuss "how" rather than "whether" HIV causes
AIDS. They argue that it is not necessary to understand HIV pathology,
or how a latent virus kills, in order to claim etiology (7, 14, 32, 51).
Therefore, many different mechanisms, including ones in which HIV is said
to depend on cofactors to cause AIDS, have been discussed (6, 12, 31, 32,
35, 61, 91) to explain how the virus supposedly kills at least 10 [4th
power] times more T cells than it actively infects (26-28, 71-74). Yet
all speculations that HIV causes AIDS through cofactors cast doubt on HIV
as a cause of AIDS, until such factors are proven to depend on HIV.
In contrast to what is claimed for HIV, there is unambiguous genetic
evidence that biochemical activity in or on more cells than the body can
spare or regenerate is absolutely necessary for viral or microbial pathogenicity.
Examples are transformation-defective mutants of Rous sarcoma virus (166)
and replication-defective mutants of cytocidal viruses (87). If latent
viruses or microbes were pathogenic at the level of activity of HIV, most
of us would have Pneumocystis pneumonia (80-100%) (167), cytomegalovirus
disease (50%) (88), mononucleosis from EBV (50-100%) (see above; ref. 88),
and herpes (25-50%) (88) all at once, and 5-10% also would have tuberculosis
(168), because the respective pathologens are latent, immunosuppressed
passengers in the U.S. population at the percentages indicated. Since we
can now, through molecularly cloned radioactive probes, detect latent viruses
or microbes at concentrations that are far below those required for clinical
detectability and relevance, it is necessary to reexamine the claims that
HIV is the cause of AIDS.
In response to this, it has been argued that a biochemically inactive
HIV may cause AIDS indirectly by a mechanism(s) involving new biological
phenomena (12, 14, 31, 32). This is argued even though HIV is like numerous
other retroviruses studied under the Virus-Cancer Program during the past
20 years (17, 140), which are only pathogenic when they are biochemically
active (23). Nevertheless, some retroviruses (23) and DNA viruses (e.g.,
hepatitis virus in hepatomas (169)) are thought to cause tumors indirectly
by converting, by means of site-specific integration, a specific gene of
a rare infected cell to a cancer gene. Such a cell would then grow autonomously
to form a monoclonal tumor, in which the virus may be inactive and often
defective (17, 23, 140, 169). However, such highly specific, and hence
rare, virus-cell interactions cannot explain the loss of billions of cells
during a degenerative disease like AIDS. It is also hard to accept that
HIV could cause AIDS through a T-cell autoimmunity (12, 31, 32, 170), because
it reaches far too few cells to function as a direct immunogen and because
it is unlikely to function as an indirect immunogen since it is not homologous
with human cells (73, 75, 77). Further, it is extremely unlikely that any
virus could induce autoimmunity, which is a rare consequence of viral infection,
as efficiently as HIV is thought to cause AIDS, namely in 50-100% of all
Not All AIDS Diseases Can Be Explained by Immunodeficiency.
Clearly, immunodeficiency is a plausible explanation for the microbial
and viral AIDS diseases (5) and Pneumocystis pneumonia. However, the effective
immunity against HIV, which defines AIDS, together with those against cytomegalovirus,
herpes simplex virus, hepatitis virus, and other viruses (3, 23, 61, 94),
is hard to reconcile with acquired immunodeficiency. One would have to
argue that T-cell depletion in AIDS is highly selective in order to allow
Pneumocystis but not HIV or other viruses to become active. If HIV were
able to induce T-cell immunodeficiency against itself, its titer during
AIDS should be as high as it is in cultures of infected human monocytes
-- namely, up to 10 [6th power] infectious units per milliliter (see above),
just as high as the titers of all other retroviruses when they are pathogenic
in animals (23).
Moreover, immunodeficiency does not explain AIDS neoplasias such as
lymphomas or Kaposi sarcoma, which may be a hyperplasia (175, 178). The
hypothesis that cancers reflect a defective immune system, the immune-surveillance
hypothesis (176), has been disproven through athymic (nude) mice, which
develop no more cancers than other laboratory mice (177). In fact, no immunodeficiency
was observed in HIV-infected African patients who had Kaposi sarcomas (157,
158). In addition, Kaposi sarcoma tissue does not contain any HIV (23,
178, 179). Immunodeficiency also cannot explain dementia; nor can dementia
be explained by HIV infection of neurons, because retroviruses are dependent
on mitosis for infection (17, 23, 139, 140) and neurons do not divide (169).
HIV would indeed by a mysterious virus (31) to kill T cells and neurons
that are not infected and, at the same time, to induce hyperplastic or
neoplastic growth of other cells that are also not infected.
HIV Is Not a Rational Basis for AIDS Therapy.
Since there is no proven mechanism of HIV pathogenesis, HIV is not a
rational basis for the control of AIDS. Thus the treatment of symptomatic
and even asymptomatic HIV carriers with azidothymidine (AZT) (7, 39) cannot
be justified in terms of its original design, which is to inhibit HIV DNA
synthesis by chain termination (171). Even if HIV were to cause AIDS, it
would hardly be a legitimate target for AZT therapy, because in 70-100%
of antibody-positive persons proviral DNA is not detectable (73, 75, 187)
without amplification (77), and its biosynthesis has never been observed.
Nevertheless, AZT has been claimed to have beneficial effects for AIDS
patients on the basis of a 16- to 24-week double-blind trial (194). However,
AZT, originally developed for chemotherapy by terminating cellular DNA
synthesis, efficiently kills dividing blood cells and other cells (39,
84, 172-174, 189, 193, 195) and is thus directly immunosuppressive. Moreover,
the immediate toxicity of AZT (174, 189, 193, 195) suggests that this trial
could hardly have been double-blind and hence unbiased.
What Are the Causes of AIDS?
I propose that AIDS is not a contagious syndrome caused by one conventional
virus or microbe, because no such virus or microbe would average 8 years
to cause a primary disease, or would selectively affect only those who
habitually practice risk behavior, or would be able to cause the diverse
collection of over 20 degenerative and neoplastic AIDS diseases. Neither
could a conventional virus or microbe survive if it were as inefficiently
transmitted as AIDS, and killed its host in the process. Conventional viruses
either are highly pathogenic and easy to transmit or are nonpathogenic
and latent and hence very difficult to transmit (153). Conventional viruses
or microbes also exist that cause secondary -- or even primary -- diseases
long after infection, but only when they are activated from dormancy by
rare acquired deficiencies of the immune system (86). Such opportunistic
infections are the consequence rather than the cause of immunodeficiency.
Since AIDS is defined by new combinations of conventional diseases,
it may be caused by new combinations of conventional pathogenic factors.
The habitual administration of factor VIII or blood transfusions (94, 161)
or of drugs (47, 64, 160, 190-192), chronic promiscuous male homosexual
activity that is associated with drugs (64, 160, 191), numerous acute parasitic
infections, and chronic malnutrition (159, 160) -- each for an average
of 8 years -- are factors that appear to provide biochemically more tangible
and plausible bases for AIDS than an idle retrovirus. Indeed, the correlation
between AIDS and such factors is 95% (4, 5). Among these factors, EBV,
cytomegalovirus, herpes simplex virus, and administration of blood components
and factor VIII have all been identified as causes of immunodeficiency
not only in HIV-positive, but also in HIV-negative, hemophiliacs (11, 61,
94, 161). In fact, the dose of factor VIII received was found to be directly
proportional to subsequent immunodeficiencies (94, 161). The habitual admission
of narcotic toxins appears to play a major immunosuppressive role in the
U.S. and Europe (11, 64). About 30% of the American AIDS patients are confirmed
users of injected drugs (4, 47). Because of the difficulties in assessing
drug data (47, 91, 92), it is probable that the percentage who use injected
and/or noninjected drugs is even higher (64, 155, 185, 190-192). For example,
nine different drugs were used in combination by a cohort of antibody-positive
homosexuals in San Francisco (160). Again there are quantitative drug-AIDS
correlations. For example, the decreased use of nitrite inhalants was shown
to correlate with the decreased incidence of Kaposi sarcoma in homosexuals
(190, 191). Moreover, that the Kaposi sarcoma cases decreased exactly with
the use of nitrites, rather than lagging behind it by 8 years as would
be expected from the presumed 8-year latent period of HIV, argues directly
against a role of HIV in Kaposi sarcoma. Further, it has been documented
that protein malnutrition and parasitic infections are the most common
causes of T-cell immunodeficiency world-wide, particularly in developing
countries (181). Unlike HIV, the specifics of these risk factors provide
a plausible explanation for the risk specificity of AIDS diseases. The
long and unpredictable intervals between the appearance of antibody to
HIV and the onset of AIDS would then reflect the thresholds for these factors
to cause AIDS diseases, rather than an unlikely mechanism of HIV pathogenesis.
In response to this view it is often pointed out that AIDS risks have
existed for a long time (55, 59), whereas AIDS is said to be a new syndrome
(3, 7, 12-14). However, this argument fails to consider that the major
risk groups -- male homosexuals and intravenous drug users -- have only
become visible and acceptable in the U.S. and in Europe during the last
10 to 15 years, about the same time that AIDS became visible. Acceptability
facilitated and probably enhanced risk behavior, and thus the incidence
of the many diseases now called AIDS. Increased consumption of drugs was
reported to have increased the number of drug-related deaths, although
unconfirmed HIV infections were the preferred interpretation (190, 192).
Moreover, the particular permissiveness toward these risk groups in metropolitan
centers encouraged the clustering of cases that was necessary to detect
AIDS. Further, it has been pointed out that slim disease, fever, and diarrhea
in Africa are not a new epidemic, but old diseases under a new name, caused
by previously known infectious agents and malnutrition (11, 64, 98, 182).
This analysis offers several benefits. It ends the fear of infection
by HIV, and particularly of immunity to HIV, because it proves that HIV
alone is not sufficient to cause AIDS. To determine whether HIV is necessary
for AIDS, controlled, randomized analyses (196) either of risk takers who
differ only by the presence of antibody to HIV or of antibody-positive
individuals who differ only in taking AIDS risks must be carried out. Moreover,
assessment of a pathogenic potential of HIV would depend on evidence that
the life-span of antibody-positive risk takers is shorter than that of
antibody-free controls. In addition, it should be determined whether, prior
to 1981, AIDS-risk takers ever developed what are now called AIDS diseases.
This analysis also suggests studies on how the nature, frequency, and duration
of AIDS risks generate risk-specific diseases. This analysis also suggests
studies on how the nature, frequency, and duration of AIDS risks generate
risk-specific diseases. Such studies should include persons treated with
AZT before or after AIDS symptoms to assess the AIDS risks of AZT. To this
end, diseases should be reported by their original names (8-10), rather
than as AIDS (4) because of their association with antibody to HIV. Finally,
this analysis suggests that AIDS prevention efforts be concentrated on
AIDS risks rather than on transmission of HIV (43).
This article is dedicated to the memory of Charlotte Friend.
I am very grateful to Klaus Cichutek, Dawn Davidson, Thelma Dunnebacke-Dixon,
David Goodrich, Steve Martin, Seth Roberts, Harry Rubin, Russell Schoch,
Gunther Stent, and Ren-Ping Zhou (Berkeley); Jad Adams and Mike Verney-Elliott
(London); Ruediger Hehlmann (Munich); George Miller (New Haven); Nicholas
Regush (Montreal); and Harvey Bialy, Celia Farber, John Lauritsen, Nathaniel
Lehrman, Katie Leishman, Anthony Liversidge, Craig Schoonmaker, and Joseph
Sonnabend (New York) for encouragement, critical information, discussions,
or reviews of this manuscript and, above all, for common sense. Further,
the Chairman of the Proceedings Editorial Board is acknowledged for providing
critical reviews and comments. P.H.D. is supported by Outstanding Investigator
Grant 5-R35-CA39915-03 from the National Cancer Institute and Grant 1547AR1
from the Council for Tobacco Research.
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* This paper, which reflects the author's views on the
cause of AIDS, will be followed in a future issue by a paper presenting
a different view of the subject.