Virus and Acquired Immunodeficiency
Syndrome: Correlation But Not Causation1,2
By Peter H. Duesberg
Acad. Sci. USA, Vol. 86, pp. 755-764, February 1989
Contributed June 14, 1988; revision received October 21, 1988
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 epidemiological, 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 healthy 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 ²1 of every 104 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-I 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.
thing is to not 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 pneumonia, 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).
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 antibodies
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). "... Patients are excluded as
AIDS cases if they have a negative result(s) on testing for serum
antibody to HIV, do not have a positive culture for HIV" (3).
If confirmed, HIV would be the first clinically relevant retrovirus
since the Virus-Cancer Program called for viral carcinogens in 1971
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).
adoption of the virus-AIDS hypothesis by the U.S. Department of
Health and Human Services (16) and by 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
Account for the Loss of T Cells and the Clinical Course of AIDS.
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
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).
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.
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 107 lymphocytes, millions of these cells
must be cultivated in vitro to reactivate the virus (86).
Not Reproduce AIDS When Inoculated into Animals or Humans. Animal
infections. Koch's third postulate calls for inducing the disease
by experimental infection of a suitable host 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.
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).
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
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.
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
of a Viral Pathogen
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.
of the 30 million people in Zaire have been reported since 1985
to be antibody-positive (46, 98, 184). However, 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 9000 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, 12-14).
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%.
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.
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).
HIV is very inactive even when it is said to cause fatal immunodeficiency.
Viral RNA synthesis is detectable in only 1 of 104 to 106 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
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 106 HIV particles, given 10-3 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.
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 disease.
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 virus 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, 115-119).
viruses are eliminated by immunity, some, such as the retroviruses
and the herpes viruses, 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 herpes viruses 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 macrophages
(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 104 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.
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 of HIV.
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, 87).
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 104 to 105 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 102 to 105 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 immunity.
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).
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 a 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 stimulating 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,
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 106 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 host cells.
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 cannot be relevant 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, 37,188). 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 106 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
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 Pneumocystis pneumonia
has shifted up from 42% to 64% (8), while the alleged cause, HIV,
has remained the same.
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
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.
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).
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.
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
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). However, 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 lymphoma-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.
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 104 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.
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 pathogens 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.
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 last 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 infections.
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 106 infectious units per milliliter (see
above), just as high as the titers of all other retroviruses when
they are pathogenic in animals (23).
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 be 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.
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
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.
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.
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 worldwide,
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.
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
prefered 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).
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. 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).
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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