virus and acquired immunodeficiency syndrome: Correlation
but not causation*
Proc. Natl. Acad. Sci. USA
Vol.86, pp. 755-764, February 1989
Peter H. Duesberg
Department of Molecular Biology,
University of California, Berkeley, CA 94720
by Peter H. Duesberg, June 14, 1988; revision received October 21,
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.
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).
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).
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.
Not Meet Koch's Postulates
Account for the Loss of T Cells and the Clinical Course of AIDS.
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 behind infection.
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
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).
Not Reproduce AIDS When Innoculated into Animals or Humans.
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
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).
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
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).
Not Meet Established Epidemiological, Biochemical, Genetic, and
Evolutionary Criteria of a Viral Pathogen
of AIDS and HIV Are Not Consistent.
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, 12-14).
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.
Despite Minimal Viral Activity.
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 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.
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.
Despite Antiviral Immunity.
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
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, 115-119).
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.
of 2 to 15 Years Between Infection and AIDS Are Incompatible with
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 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 immunity.
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).
of How HIV, a Noncytocidal Retrovirus, Is To Cause the Degenerative
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 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 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.
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.
of an AIDS Virus with Country- and Risk-Specific Pathologies and
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.
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.
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.
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.
Etiology Depends on Evidence for Activity.
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.
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.
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 infections.
AIDS Diseases Can Be Explained by 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).
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.
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.
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 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.
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).
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).
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.