Genetica 95: 173-193, 1995
THE EPIDEMIOLOGY AND TRANSMISSION OF AIDS: A HYPOTHESIS
LINKING BEHAVIOURAL AND BIOLOGICAL DETERMINANTS TO TIME, PERSON AND PLACE
Gordon T. Stewart
Emeritus Professor of Public Health, University of Glasgow,
Glasgow G12 8QQ, UK
Present address: Glenavon, Clifton Down, Bristol BS8 3HT, UK
Epidemiologically, the Acquired Immune Deficiency Syndrome, AIDS, is
transmitted and distributed in the USA and Europe almost entirely in welldefined
subsets of populations engaging in, or subjected to, the effects of behaviours
which carry high risks of genital and systemic infections. The persons
predominantly affected are those engaging in promiscuous homosexual and
bisexual activity, regular use of addictive drugs, and their sexual and
recreational partners. In such persons and in subsets of populations with
corresponding lifestyles, the risk of AIDS increases by orders of
magnitude. Because of continuity of risk behaviour and of associated indicator
infections; the incidence of AIDS over 35 year periods is predictable
to within 10% of actual totals of registered cases in the USA and UK. Secondary
transmission of AIDS beyond these groups is minimal or, in many locations,
absent. There is no indication of appreciable spread by heterosexual transmission
to the general population.
The Human Immunodeficiency Virus, HIV, is transmissible to some extent
in general populations, and more so among promiscuous persons. It may cause
viraemia, lymphadenopathy and latent infection (HIV disease) in anyone.
In persons engaging in risk behaviours which themselves alter or suppress
immune responses, it can interact with MHC, antibodies to other organisms
and to semen, and other allogenic antigens to initiate a programmed death
of CD4 lymphocytes and other defensive cells, as in grafthost rejections.
This occurs also in haemophiliacs receiving transfusions of blood products,
and is more pronounced in persons with reactive HLA haplotypes. The susceptibility
of particular subsets of populations to AIDS is thereby largely explained.
But these changes occur in the absence of HIV, and so do Kaposi's sarcoma,
lymphadenopathies and opportunistic infections which are regarded as main
indicators of AIDS. The hypothesis that HIVI can do all this by itself
and thereby cause AIDS is falsifiable on biological as well as epidemiological
An alternative hypothesis is proposed, linking the incidence of AIDS
to the evolution of contemporary risk behaviour in particular communities
and locations in the USA, UK and probably in most of Europe. It does not
pretend to explain the reported incidence of AIDS in Africa and other developing
regions where data are insufficient to provide validation of the pattern
of disease and contributory variables.
The immediate, practical implication of this alternative hypothesis
is that existing programmer for the control of AIDS are wrongly orientated,
extremely wasteful of effort and expenditure, and in some respects harmful.
In 1984, a US Secretary of State announced that a retrovirus then named
HTLV3, isolated from one patient in Paris, was the unique cause of loss
of immunity in a severe infectious disorder first described in 1981 in
some homosexual men and drug addicts admitted with unusual symptoms to
hospital in New York City and California. Since then, there has been a
world wide consensus in medical science and beyond that this retrovirus,
renamed HIVI, and its innumerable variants are the unique cause of
a more complex and extending range of disorders classified and repeatedly
reclassified as the Acquired Immune Deficiency Syndrome, AIDS. When
this consensus was challenged by P.H. Duesberg in 1987 (see below), R.C.
Gallo, the chief proponent of the claim for HTLV3, and leaders of the consensus
replied in a Forum reported by Science Magazine (1988;241;514) that the
'Strongest evidence that HIV causes AIDS' came less from isolates of the
virus itself than from prospective epidemiology. Having been engaged in
epidemiological work which suggests the reverse, I then began a long struggle
to persuade the immense epidemiological sector of the consensus that this
assertion, no less than the microbiological evidence of causation of AIDS
by HIV, merited reconsideration.
When Duesberg challenged the HIV hypothesis in 1987, the epidemiological
evidence depended essentially upon a correlation between antibodies to
HIV and a diagnosis of AIDS. This was a circular argument since, after
1984, seropositivity to HIV mandated a diagnosis of AIDS in patients
with a scheduled range of diseases, whether or not they were in risk groups.
In 1989, a formidable defence of the epidemiological consensus was presented
by the Royal Society of London in a Symposium (Cox, Anderson & Hillier,
1989) of invited papers which analysed the epidemic of AIDS to date in
the UK and made predictions about its incidence through 1992. These analyses
and predictions, like those of a preceding official Report (UK Dept. of
Health and the Welsh Office, 1988), rested upon assumptions not only that
HIV was the essential cause of AIDS in all its forms but also that all
who were seropositive would get AIDS which would then cause epidemics
of tens of thousands of cases by heterosexual transmission in the general
population of the UK.
The assumption that HIV would spread by heterosexual transmission was,
to a limited extent, correct but predictions of similar spread of AIDS,
as in the London Declaration of 1988, from the WHO (Mann, 1989; Sato, Chin
& Mann, 1989) and by the Advisory Committee on Dangerous Pathogens
(1990) were numerically exaggerated (Table 1), as were actuarial and other
projections used for planning and estimates of spread outside the original
risk groups of homosexual men and drug addicts. They were particularly
wrong (Table 2) in the prediction that heterosexual transmission of AIDS
in the general population would give rise to a general epidemic (Anderson
& May, 1987; Public Health Laboratory Service, 1990). What the epidemiological
evidence did show in the USA, in the UK, and most of Europe and Australasia,
was a continuing increase of AIDS in the original high risk groups. This
trend is so consistent that, even in New York City, an original epicentre
of AIDS, a regression model (Stewart, 1992a, 1993a) of incidence over units
of time since 1983 predicted in 1989 a cumulative total of 45,487 cases
by the end of 1992 (N = 44,231). Predictions for the intervening years
were correct to within 10% of registered cases though, in 1993, there was
a departure from linearity caused entirely by reclassification of AIDS
by the CDC in that year (see below) to include all cases of carcinoma of
the cervix, tuberculosis and many bacterial pneumonias in HIVseropositive
patients (Fig. 1). In the UK, with a much lower incidence, regression models
through 1993 and to date are equally accurate
(Fig. 2). AIDS is a disease which began and spread in males. In females
and their infants outside risk groups, the incidence of AIDS after ten
years is negligible in the UK as in New York City (Table 2).
All of this is verifiable in the registrations published by official
surveillance in the USA and UK. The epidemiological evidence in New York
City does, however, indicate an increase of AIDS by presumed heterosexual
transmission in men and women in the blackHispanic ethnic minorities
in parts of Manhattan, Brooklyn and Queens, especially if they use drugs
(Stoneburner et a/., 1990). To investigate the role of HIV in this,
Pagano et al. (1991) used an elaborate model with three levels of
seroprevalence to estimate the incidence of AIDS through 1995. Their
estimates for 1991 ranged from 16,106 assuming no new infections to 29,962
assuming 10,000 new infections annually (N = 6,800). Fordyce et al.
(1991) estimated the cumulative incidence of AIDS in female partners
of drug addicts to be 3,900 (N = 4091) from formulae based on conditional
probabilities of uninfected women acquiring HIV from infected male partners.
But if P/ivdu, the probability that a woman in New York will have a drug
user as a sex partner, is replaced in the model by the alternative probability
P/hiv that she is equally or more likely to be infected by any man who
is HIVpositive, the estimate of AIDS again becomes exaggerated.
Incidence in the UK expressed as a rolling average or periodically since
1982 (Stewart, op. cit.) and despite considerable fluctuations in reporting
follows the same close correlation with units of time (r = 0.97). Regression
accurately predicted about 3,000 cases by December 1989 (N = 2,830), 1,254
in 1991 (N = 1,275), 1,365 in 1992 (N = 1,418) and in cumulative total,
excluding visitors, of 6,540 (N = 6,929, including visitors) by the end
of 1992 (Tables I and 2, Fig. 2). This is very much less than the range
of 3,810 4,950 predicted by Anderson (2) for the year 1992 which
gave a cumulative total, for planning, of 12,010 15,190 cases in
the UK by December 1992 and much higher totals thereafter. In contrast,
the regression model predicted only 1,554 new cases (excluding visitors)
in 1993 when the actual total (including visitors) was 1,619, to give a
cumulative total by 1994 of 8483 cases (N = 8529), over 3,000 less than
the lowest official estimate for 1992.
The large errors in these predictions In Britain and in the USA are
inherent. They derive from acceptance of the hypothesis that continuing
sexual transmission of HIV is the main determinant of the incidence of
AIDS. This led to further assumptions that heterosexual transmission will
increase until females are equally at risk, that all who are infected with
HIV will develop AIDS sooner or later and die, and that mathematical models
based on this reasoning will predict the course of events correctly, within
wide limits. The passage of time and the data since 1989 in the USA and
in Britain falsify all this (Tables I and 2).
So also do backprojections for the UK, projections by Bregman and
Langmuir (1990), based on Farr's Law of Epidemics, for the USA and estimates
using sociogeographic data in New York City (Wallace, 1991). But predictions
based on regression equations (Figs. I and 2) are more reliable because
they leave less than 10% of residual variance in incidence since 1983 unexplained.
Such accuracy in a deterministic model is highly unusual. The most obvious
reason is that transmission and expression of AIDS is restricted to subsets
of the population which engage in, or are exposed to, the effects of continuing
riskbehaviour (Stewart, 1990a, 1991, 1992a). Even in those subsets,
the incidence may now be decreasing in the USA and the UK. The accuracy
of predictions from raw data by regression methods is consistent with the
finding that, while HIV1 has already spread widely in both sexes because
of its presence in genital secretions and in needles shared by drug addicts,
the occurrence of AIDS beyond risk groups, as predicted in al1 of ficial
surveys, is low or absent even in communities where HIV 1 is prevalent.
The differences in levels of risk, calculated from best estimates of relevant
denominators, are enormous (Table 3) and need much more attention.
The obvious conclusion is that, in such communities, AIDS cannot develop
unless other interacting causes of immunosuppression and cachexia
are present. Registration data from the USA since 1985 show that prevalence
of HIV and AIDS is strongly influenced by ethnic, urban, economic, social,
occupational and mobility factors. In New York City, the situation is dominated
by the fact that 60% of adults and 90% of infants with AIDS are in Black
or Hispanic communities and by the 33fold difference in rates of disease,
from < 50 to > 1,500 per 10,000 adults, in different districts of
the city (Table 2). In the UK, analytical data are much less precise but,
to 30th June 1992, 1,354 cases of AIDS (38% of the cumulative total for
Britain) were reported from NW London; 94% of these cases were male
and 91 % of them homosexual. Despite this prevalence of AIDS and also of
HIV seropositivity, at least 20 times higher than the remainder of Britain,
there were only 31 cases of AIDS in women transmit ted by
(presumed) heterosexual intercourse out of 401 who were seropositive. Infants
born in London in 1992 were much more often seropositive than those born
outside but, because surveillance is voluntary, unlinked, anonymous and
confidential, it is impossible to know how this relates to the risks, status
and treatment of the 50 mothers who have given birth from 198293 to
babies who developed AIDS (about 1:120,000 births). In southeast England
generally, it was estimated that 92% of neonatal seropositives and 7 out
of 8 babies who developed AIDS in the first year of life came from mothers
who were born in Africa (Aces, Parker & Cubitt, 1992). There is clearly
a pressing need for a more informative data base and correlation matrix
in the UK but, even in these limited data, it would appear that there is
no appreciable spread of AIDS to infants from their mothers in the general
population outside specified risk groups in or from welldefined locations.
The current hypothesis
The hypothesis that HIV is the unique cause of AID is an inductive generalisation
based on a few agree facts and an acceptance in medical, sociological an
political circles of corroborative reasoning, conjectur and consensus.
The facts (BarreSinoussi, Cherman & Rey, 1983; Gallo, Salahuddin
& Popvic, 1984; Dal gleish et al., 1984; Levy & Chimabukuro
1985; He Pomerantz & Kaplan, 1987; Hanafusa, Pinter & Pull man,
1987; Gallo, 1987) are that (i) HIVs can be isolated from, or identified
by biochemical probes in celh blood and secretion of an (unknown) proportion
c patients with AIDS; (ii) in patients with AIDS wh are tested serologically,
antibodies specific for antigens prepared from envelopes of the original
isolate of LAV 1/HTLV III are usually detectable; (iii) in term of this
test, there is a correlation between the presenc of HIV and AIDS in a community;
(iv) HIVs appec to be transmitted from persontoperson by anal
an vaginal intercourse, or parenterally via infected needles or blood transfusion,
or congenitally; and (v) HIVs have high affinity for, and fuse with specific
CD4 membrane receptors on helper Tlymphocyte and other mononuclear
cells, transcribe their RNA int the DNA of the cells' nuclei and form virions
which can infect other Tlymphocytes. The reasoning (Ho Pomerantz &
Kaplan, 1987; Blattner, Gallo & Tenil 1988; Institute of Medicine,
1988; Baltimore & Feir berg, 1989; Fauci, 1988) is that HIVs can thereby
weaken or destroy cellmediated immunity, and that persons thus affected
always or almost always succumb to a specific syndrome of generalised immune
deficiency which then renders them susceptible to other, opportunistic
infections and to various disorders of lymphoid cells and vital processes
with fatal or nearfatal results. The conjecture of these authors and
very many others is that infection with HIV is necessary and sufficient
to explain this pathogenesis, irrespective of riskbehaviour. The consensus
of the medical and scientific establishment, and practically all health
authorities is that epidemiological evidence and predictions support this
reasoning, and that any departure from it is heresy, a threat to public
safety and efforts to control a dangerous epidemic, and to dedicated research.
Weakness in the HIV hypothesis
Despite this overwhelming consensus, or perhaps because of it, there
are many uncertainties and flaws of reasoning in this hypothesis on epidemiological,
clinical and microbiological grounds. Epidemiologically, the data presented
above falsify the assumption that AIDS is spreading in general populations
in the USA and UK by heterosexual transmission of HIV. The salient point
that AIDS was described (Gottlieb, 1981; and see report from the CDC, Atlanta,
Gal, from California State Health Department and from New York City, Dept.
of Health) simultaneously in California and in New York City as focal incidents,
with no evidence of anything comparable elsewhere at that time, is often
overlooked. The first cases were registered in San Francisco on July 1st,
1981. By March 1985. 1.000 cases had been registered, of which 992 (99%)
were male and 98% homosexual or bisexual with multiple partners, with a
very high prevalence of gonorrhoea, syphilis, hepatitis and other sexuallytransmissible
infections, with 13% using intravenous drugs and 98% resident in the Bay
area. The position in 1992, in the UK, most of Europe, Australasia and
North America at least, is that AIDS is still predominantly a disease of
men (Table 2) and that the women who acquire it, at a much lower incidence,
are those who expose themselves to high risks of infections from partners
with AIDS or at risk of AIDS because of homosexual and bisexual behaviour,
and from use of toxic drugs.
In female prostitutes, who are a risk group for any sexuallytransmitted
disease (STD), HIV infection and AIDS are prevalent in African cities (see
WHO: weekly epidemiological reports) but not in North America or Europe
unless they use drugs habitually or have other STDs. Seale (1988) suggested
that, for this reason, AIDS did not qualify clinically for classification
as an STD. and also because it is essentially 'A bloodborne infection which
is transmitted only with considerable difficulty during biological sexual
intercourse' from which he excluded penileanal intercourse.
This would be consistent with the findings, in multicenter prospective
and many other studies (Marmor, FriedmanKien & Laubenstein, 1982;
Shilts, 1987; Gunzburg, Fleming & Millar, 1988; Detels, English &
Visscher, 1989; Ma & Armstrong, 1989; Beral, Bull & Darby, 1990)
of homosexual men, that rectal trauma and infections from bleeding, douching,
fisting and other traumatic and anoerotic acts are associated with
progression to AIDS and ARCs.
In Africa, the Caribbean and Asia, notifications of seropositivity to
HIV and of AIDS to the WHO are increasing sharply. The epidemiological
and clinical patterns, at face value, are different from those of the western
world. Cases are reported with equal frequency in males and females and
homosexuality and use of drugs are uncommon as risk factors. In place of
the opportunistic infections reported in developed countries, tuberculosis,
diarrhoeal diseases, malnutrition, exhaustion and early death are the main
clinical features. Occurring as they do on a considerable scale in young
men and women, this is widely regarded as a new, uncontrollable epidemic
in many subSaharan countries. Details of CD4 counts, isolation of
HIV and other tests are seldom available.
There is considerable genetic divergence in the comparatively small
number of strains of HIV isolated in third world countries (Louwagie, McCutchan
& Van der Groen, 1992; Pfutzner, Dietrich & von Eichel, 1992).
As in the USA and Europe, AIDS is very uneven in distribution. Originally,
it was reported from Uganda (Serwadda, Sewankambo & Carswell, 1985)
as a localised, wasting 'Slim' disease, but now it has become an acute
infection strongly linked with tuberculosis (KonoteyUhulu, 1989; Berkley,
WidiWirski & Odware, 1989; de Cock et al., 1992). Along
with other STDs, AIDS is increasingly prevalent in certain cities on the
international travel routes of persons who sample the local risks, and
convey their own infections and riskbehaviour to local populations.
Hence the ominous spread in Africa via truckroutes, and in the UK
in certain immigrants, visitors, returning travellers and their domestic
partners (Hawkes et al., 1992).
AIDS was not described in Africa until 1984, some years after the first
occurrences in white men in the USA and in black Haitian immigrants in
New York City. This, together with the prevalence of seropositivity to
HIV in unconfirmed ELISA tests in Zaire in 1985, led the consensus to the
belief (Gallo, 1987; Mann, 1989) that AIDS had therefore originated in
Africa. A wide search was therefore made to find support for a subsidiary
hypothesis that AIDS had spread somehow from Africa to the USA, if not
to the rest of the world. The reasoning is that HIVs evolved like Simian
Immune Deficiency Viruses (SIVs) latterly identified in nonhuman primates
in Africa, either by phylogenetic separation of a retrovirus from a common
progenitor in the distant past, or by crossspecies transfer to humans
more recently (McClure & Schultz, 1989). If this is shown to be genetically
plausible, or if immune deficiency occurs naturally in nonhuman primates
infected with SIVs, or artifically with HIV in the absence of other infections,
the argument might become credible. But a very extensive search has revealed
no common progenitor, and no link between any SIV and HIV 1 in Africa (Scale,
1988). Irrespective of the simian or other origins of HIVs the view that
AIDS in the clinical pattern now observed was already prevalent in Africa
is entirely speculative. There is no comparable study of the alternative
possibility that AIDS might have travelled from its observed origin in
the USA in 1981 somehow to Africa.
Classification of AIDS
AIDS is registered internationally as if it were a single infectious
disease, and is surveyed accordingly, that is to say as if it were a selfdefining
dependent variable. But the original empirical classification by the US/CDC
accepted internationally in 1983 was expanded in 1987 to schedule a range
of neoplasms, infections, malnutrition and dementia in which seropositivity
to HIV, with or without riskgroup identification, or these symptoms
without seropositivity in risk groups were made eligible for classification
as AIDS. This increased the size of the epidemic in the USA by about 27%.
To this list of 'indicator' diseases, a further revision
in 1992, synchronous with identical changes in the International Classification
of Diseases, added cancer of the cervix, tuberculosis and other diseases
in persons who are seropositive. This has already added numerous females
to the incidence of AIDS (Fig. 1) and manufactured an epidemic in women
which is, otherwise, conspicuous by its absence (Stewart, 1992b). To add
to the confusion, there are growing doubts (Couruce, Muller & Richard,
1986; Meyer & Panker, 1987; Midthum, Garrison & Clements, 1990;
Mortimer, 1991; Davey, Dayton & Metcalf, 1992; PapadopulosEleopoulos,
Turner & Papadimitriou, 1992) about the lack of an independent goldstandard
validator, and therefore about the specificity of serotests for HIV,
even with double testing by immuneabsorption and blot, in the presence
of other infections and immunological disorders, especially in tropical
countries. The fall in CD4 lymphocytes, required for validation, but seldom
performed outside specialised units, is also a nonspecific event (Drew,
Mills & Levy, 1985; Jason, Holman & Evatt, 1990; RootBernstein,
1993) which occurs in many other infections and after infusions of foreign
protein, e.g. to haemophiliacs (Carr, Edmond & Prescott, 1984).
In centres with expertise and facilities, surveillance of AIDS is monitored,
with appropriate checks and tests. In reports from such centres, the pattern
of AIDS is consistent and predictable, as above. But HIVs can be isolated
from persons with and without AIDS or related conditions (ARCs). The great
majority of seropositives show no signs of disease. To accommodate the
continuing absence of AIDS in such persons, the 'incubation' period between
infection and the onset of disease has been extended to 15 years or more
in the 1987 and subsequent classifications by the CDC and WHO. This had
led to a muddled situation in which anyone with the wide spectrum of symptoms
and signs in these various classifications who has antibodies to antigens
in any one of the several antigenkits, or a fall in CD4 counts, is
liable to be diagnosed as AIDS: so are person in risk groups with some
of the signs, whether or not they are seropositive, and seronegatives not
in riskgroups with signs who then become seropositive. The Revised
Classification now in use raises to 28 (in Section B2024) the number
of independent diagnoses that may now be registered as AIDS. Section B21.09
includes 6 specified and 3 unspecified malignancies, to which cancer of
the cervix is now added. This alone has already added thousands of cases
of AIDS to survey totals of AIDS internationally. Section B21.79 (any
cancer) and B22 (any other specified or wasting disease) in anyone who
happens to be seropositive and in many who are not, add many more. Details
of collateral or coincidental disease, and tests to exclude other
diagnoses are not required for registration, not even the CD4 (T4) lymphocyte
count, mandated by the consensus as the hallmark of AIDS. Against all logic,
this extraordinary diagnostic gallimaufry is accepted by the medical profession
and the consensus as input data, not only for surveillance, but also for
prediction of the spread of AIDS internationally.
HIVs have several properties which may relate to the pathogenesis of
AIDS (Gallo, 1987, Fauci, 1988; Evans, 1989a). In addition to thegag, pol
and env genes common to all retroviruses, they have five or more nonstructural
genes including a tat masterswitch (Carlin, Peterlin & Derse,
1992; Elangovan, Subramanian & Chinnadurai, 1992) which enable them
to regulate their replication and to delete, insert and duplicate nucleotides
so as to evade immune responses. They are naturally lymphotropic and enter
Thelper lymphocytes, among other cells, because their envelope glycoproteins
interact with specific CD4 surface receptors (Dalgleish, Beverley &
Clapham, 1985). In situ, they transcribe their RNA into the cell's
DNA and replicate to form virions which have been shown to infect monocytes
and macrophages as direct transfer (Fauci, 1988; Li & Burrell, 1992;
Innocenti, Ottoman & Morand, 1992). These migrate to other sites, including
the brain and thymus, where HIV may infect other cells, remain latent or
replicate in accordance with the interplay of positive and negative regulatory
elements in its own genome, or in those of defensive cells.
Retroviruses are characteristically latent (Duesberg, 1987; and see
Hanafusa, Pinter& Pullman, 1989). HIV is no exception in the great
majority of infected persons who remain, to date, asymptomatic. But this
unusual combination of genetic heterogeneity and antigenic variability
between strains of HIV, with mutability of nucleotide sequences within
strains and tropism for migrant cells, would seem to offer plausible mechanisms
for activation. In a search for amino acid sequences involved in cell tropism,
Cheesebro et al. (1992) found homology in macrophagetropic
clones from different patients. Tcelltropic clones were, in contrast,
highly heterogeneous. Sitespecific mutations in amino acid sequences
in the V3 region of HIV isolates appeared to be responsible for these tropisms.
This hypervariable domain within gp 120 is recognised (Shioda & Levy,
1992) as a major determinant of the ability of HIVI to infect Tcells
and macrophages. These and other examples of genetic heterogeneity occur
within as well as between strains, so much so that HIV has been described
as a quasispecies in which no two genomes are identical (WainHobson,
1989; Vartamian, Meyerhans & WainHobson, 1992). Many are defective
and, by the same token, noninfective. Proviral sequences vary accordingly,
in the same or in successive isolates, and so do replication rates in
vivo, as disease advances. The consensus accepts these properties of
HIV as explanations of its ability to emerge from latency and of its pathogenicity.
The impetus of over 60,000 supportive papers since 1983 is formidable even
though much of it depends upon results obtained and elaborated in vitro.
There is, as in other branches of biomedical research, a greater focus
on the behaviour of the microbe than on that of the host.
The only prominent retrovirologist to question the consensus about HIV
is P.H. Duesberg of the Department of Molecular Biology at Berkeley, CA,
whose dissent is absolute. He considers that HIV is as inactive in patients
with AIDS as it is in asymptomatic carriers. In fact, he goes further and
rejects the wider claim by most virologists that latent viruses and mutated
genes can be pathogenic (Duesberg & Schwartz, 1992). His arguments,
dating from 1973 and extending far beyond the virology of AIDS, are set
out in papers (1987, 1989a) and responses to criticisms (1989b, c). His
main argument, as a retrovirologist, is directed against the central dogma
that HIV infects, multiplies in and kills enough Thelper lymphocytes
to destroy immunity. His observations that, in patients with AIDS, only
1 in 500 Tcells ever contain a provirus of HIV and that HIV cannot
kill these cells have been confirmed independently by Lemaitre et al.
(1990), the team which originally isolated HIV. His assertions that
neutralising antibodies restrict multiplication of HIV, and that it does
not have the biological energy or biochemical capacity to produce pathological
changes in vivo have been disputed (Blattner, Gallo & Tenin,
1988; Baltimore & Feinberg, 1989; Evans, 1989a, b; Weiss & Jaffe,
1990) but not falsified. He offers evidence that, when latent viruses are
reactivated after neutralisation by antibodies, this is due to independent
factors (other infections, immunosuppressive conditions) and not to mutations
in the coding region of the virus. He applies this view to other retroviruses
and diseases no less than to HIV. If he is correct, or even partially correct,
the implications will be revolutionary, for they will dismiss as circumstantial
the current beliefs that latent viruses cause specific, progressive infections
and that mutated oncogenes can ever cause cancer. HIV would then be merely
a marker for AIDS while cancers would be more likely to arise from clonal
In his original (invited) contribution to this field in 1987, Duesberg
made a critical analysis of the facts and gaps in retrovirology in this
regard. But in rejecting HIV as the cause, he also attacked the core of
the biomedical research on AIDS. This led, after a considerable delay,
to polarised reprisals with a minimum of reasoned debate (Blattner, Gallo
& Tenin, 1988; AAAS Policy Forum, 1988) on his main question about
the cytopathic effect of HIV. This is still unresolved. Even so, Duesberg
would be wrong in rejecting a pathogenic role for HIV on this account alone
because as Cheesboro et ai. (1992), among others, have shown it
can unquestionably infect monocytes and macrophages by celltocell
transmission, without killing them, and then travel in them to other tissues
where the presence of infected cells would be enough to arouse inflammatory
response and hence disease, e.g., a glial respcnse in the brain. If there
was already a latent infection with Toxoplasma, this could multiply to
cause encephalopathy which is reported in about 30% of patients with cerebral
AIDS (RootBernstein, 1993). When definitive signs of AIDS develop,
HIV replicates and releases antigen (Ho, Pomerantz & Kaplan, 1987).
It is insisted (Fauci, 1988; Baltimore & Feinberg, 1989; Weiss &
Jaffe, 1990) that this is due to a regulated change from latency to accelerated
replication, but it might equally be part of the general multiplication
of organisms which occur in any immunosuppressive state, and is a main
contributor to death in AIDS.
Duesberg's rejection of the claim that HIV kills lymphocytes per
se is supported by the work of Lemaitre, Montagnier and their colleagues
(1990) showing that the cytocidal effect of two archetypal strains of HIVs
(LAVBru of HIVI and Rod of HIV2) in vitro was lost in
the presence of noninhibitory concentrations of tetracycline analogues.
Since these compounds do not interfere with the infectivity of HIVs, the
likelihood is that a tetracyclinesensitive organism, now confirmed
as a mycoplasma, plays the role of synergistic cofactor in HIVinduced
cell Iysis. It is now thought to be identical to Mycoplasma fermentans
(incognitas) previously isolated by Lo (1986) from patients with AIDS.
This mycoplasma has been visualised, isolated in culture and identified
by DNA probes in thymus, lymph nodes, spleen, liver, brain and placenta
of patients with AIDS and from HIVnegative patients with fulminant
necrotising lesions or fatal disease in these organs. Most of the isolates
were made from tissues without necrotic or inflammatory changes but ultrastructural
examination showed, in some cases, intracellular mycoplasma and cytopathic
changes in lesions from which no other pathogens were visualised or isolated.
When injected into four monkeys, the mycoplasma caused systemic infection
followed by wasting and death in 79 months with necrotic lesions without
inflammatory reaction in which the mycoplasma (originally thought to be
a viruslike agent VLIA) was identified by immunochemistry, in situ
hybridisation and electron microscopy (Lo, Wang & Newton, 1989).
DNA from M. fermentans has been detected in the blood of seropositive
patients (Hawkins et al., 1992) but, in a systematic study of patients
attending an STD clinic, Katseni, Gilroy and Ryait (1993) found it also
in peripheral blood mononuclears, throat swabs and urine from a majority
of seronegative as well as seropositive homosexual men. This is unrelated
to the stage of disease, CD4 count and cellular HIV load in the seropositive
Mycoplasmas are notorious as contaminants in tissue cultures, especially
those requiring reinforcement. It is surprising that they have not been
reported in the innumerable other laboratories which are working round
the clock internationally with HIVs from many sources. Coming as they do
from the scientists who discovered HIV, the results quoted above prove
that HIV cannot kill Tlymphocytes without assistance from a mycoplasma.
The work of Lo and his colleagues suggests, but does not prove, that this
organism may have a synergistic or pathogenic role in AIDS.
The image of HIV as a universal pathogen is weakened further by the
fact that the strains isolated in the USA and Britain were merely subcultures
of the original strain (LAVI) isolated in 1983 from a gland from a
patient in Paris. Genuine independent isolates show continuous diversification
(Shioda & Levy, 1992; Vartamian, Meyerhans & WainHobson, 1992;
Spencer, et al., 1994). The strain type HIV1 is uncommon or
absent in some populations with AIDS in Europe and Africa, and is not crossreactive
with some prevailing strains (Quinn, Piot & MacCormick, 1987; Zwart,
de Jong & Wolfs, 1990). Genetic heterogeneity and divergent subtypes
of HIV on a wider scale, as reported above from Africa and India, might
explain the variability in symptomatology and progression of AIDS. By the
same token, this means that some strains are likely to be less, or much
less pathogenic: a prospect already verified by the survival of the majority
of infected persons in the USA and Europe. The consensus views that all
who are infected will develop AIDS and probably die is falsified on this
In the weeks after infection with HIV, some persons develop a brief
illness with fever and lymphadenopathy, similar to infectious mononucleosis.
Seroconversion then occurs, producing antibodies to HIV envelope proteins
gpl20 and p24. The majority of infected persons remain asymptomatic but
a minority, identifiable in terms of riskbehaviour and exposure to
further infections, show the hallmark fall in CD4 lymphocytes with reversal
of the T4/T8 ratio, lymphadenopathy, energy, loss of immunity, multiplication
of infection organisms including HIV, and other signs of ARCs or AIDS.
From then on, AIDS seems to be irreversible, despite specific antiviral
and symptomatic treatment. The main pathological findings are pneumonias
(Pneumocystis carinii or acute bacterial), gastrointestinal
infections (Candida, salmonellae, shigellae, entamoebae), coincident
or secondary infections of the skin, viscera and brain with other pathogenic
and opportunistic bacteria, fungi and protozoa (Table 4); and, mainly in
homosexual men, Kaposi's sarcoma. Some or all of these, along with failing
nutrition and exhaustion, lead usually to early death, though mortality
since 1983 has decreased considerably in developed countries (D'Arminio,
Vago & Lazzarin, 1992).
The occurrence of serpositivity to HIV and of AIDS following transfusions
of infected blood and blood products in some haemophiliacs and other patients,
and the apparent cessation of this after donors were screened and blood
sterilised by heat, have been advanced as selfevident and conclusive
proof of the causation of AIDS by HIV (Tsoulkas et al., 1984; Lud1am,
Tucker & Steel, 1985; Hiltgartner, 1987; Ward, Bush & Perkins,
1989; Darby, Rizza & Doll, 1989).
The existence of seroconversion and signs compatible with AIDS in recipients
of transfusions, especially in haemophiliacs, is not in doubt. But this
has to be considered against background facts. Blood transfusions are,
by themselves, wellknown to be temporarily immunosuppressive.
Patients receiving frequent transfusions are, by definition, in a risk
category. Mortality, even in the short term, is often high, inde
Homosexual and bisexual behaviour
Male homosexual relationships without anal intercourse or injections
of drugs arguably the majority (Ma & Armstrong, 1989; Stewart,
l990b) are not associated with AIDS; neither is lesbianism. AIDS began
and prevailed among those who are still at highest risk, namely the passive
male, and sometimes female, recipients of anal intercourse. This is because
the rectal mucosa and its supporting tissues are relatively fragile, designed
for excretory, not intrusive activity. When the thin submucosa is eroded
and blood vessels damaged, the tissues and blood stream are opened to invasion
by all the organisms of the faecal microflora, by the pathogens of all
the sexually transmitted diseases, and many others. The risk of trauma
and infections increases greatly with the frequency, variety (oroanal,
linguavaginal) and violence of the sexual activity and preference,
as with 'fisting' and other accessory, traumatic and contaminating procedures,
and with multiplicity of partners (Wilkins & Sonnabend, 1983; Mavligit,
Talpag & Hsia, 1984; Moss, Osmond & Bacchetti, 1987; Winkelstein,
Wiley & Padian, 1988; Sonnabend, 1989).
In such persons, the unregulated use of antimicrobial drugs for selftreatment
of gonorrhoea and other infections inhibits the competitive flora of the
intestine, opening it to bacterial and fungal superinfections which
are indicator conditions for diagnosis of AIDS. Notable among these are
Pneumocystis carinii, Candida albicans, cryptosporidia and organisms
causing chronic diarrhoca, and hence dehydration, loss of electrolytes
and exhaustion. The frequent presence of semen in the rectum and blood
adds allogenic, 'nonself' reactions which dysregulate immune responses
(Witkin & Sonnabend, 1983; RootBernstein, 1993). The faecal microflora
interacts with semen to form Nnitroso compounds, some of which are
immunosuppressive and carcinogenic (Schoental, 1988). Immunosuppression
also occurs (Newell, Mansell & Spitz, 1985; Mirvish & Haverkos,
1987; Vandenbrone & Pardoel,1989) from the use of volatile alkyl nitrites
(poppers) as aphrodisiacs and relaxants an effect which conveniently
extends to the rectal sphincter. In experimental animals, these nitrosating
agents are lymphotoxic, causing immunosuppression followed by death
from acute and chronic infections. Surviving animals sometimes develop
lymphomas (Schoental, 1988). It is possible that the conjunction of Nnitroso
compounds from semen with volatile nitrites contribute to Kaposi's sarcoma
which occurs in this context independently of
HIV (Beral, Bull & Darby, 1990). All this, combined with frequent,
promiscuous anal and bisexual intercourse with dozens or hundreds of partners
had become a way of life in the dedicated communities in which AIDS was
first observed and in those (of remarkably similar persuasions and microflora)
to which it quickly spread, internationally. Knowledge of the dangers sometimes
led to a reduction in riskbehaviour but, by this time, genital and
other infectious diseases were accepted as features of their way of life.
Transmission in heterosexuals
This is regarded by the WHO and the consensus as the usual mode of transmission
of AIDS in many third world countries. In North America and Europe, surveillance
shows some increase in AIDS occurring in both sexes from presumed heterosexual
transmission but, in the UK and USA at least, the increase is fractional,
even in persons with high risk partners (Tables 2 and 3) and in those attending
STD clinics, and is confined to major urban areas. It is uncommon in prostitutes
unless they are using drugs. AIDS in women outside the main risk groups
is minimal or zero. Since seropositivity to HIV in random samples may be
equal in the sexes, and since sexual intercourse with more than one partner
by the age of 18 is now common, the key questions arising from the absence
or infrequency of AIDS in females are if and why it occurs at all. Confidentiality
of records and lack of contacttracing deemed necessary in other STDs
preclude answers. How much of what there is has been acquired from bisexual
men, from anal intercourse, from undeclared use of drugs? But a thorough
search of registration data in key areas of the USA and UK (Stewart, 1992a,
1993a) and of a vast international literature (RootBernstein, 1993)
discloses no convincing reports of outbreaks of AIDS in females exempt
from riskbehaviour or from circumstances which impose risks upon them.
Use of psychoactive and immunotoxic drugs
An amalgam of debilitating infectious and wasting disease had been noted
from the late 1960s onward in young adults and adolescents who injected
themselves repeatedly with impure and unsterile, illegallyobtained psychoactive
drugs (Gay, 1972; Moss, 1987; Selwyn, 1989). This practice causes bizarre,
often intractable infections in the blood and various organs from contaminants
in the drugs. Needlesharing, promiscuous sexual intercourse and general
disregard of hygiene a notorious feature of the drug scene everywhere
leads to sharing also of whatever infections are endemic in that
community PCP, HIV, hepatitis, herpes, EBV, VZ and CMV which may
impair cellmediated immunity and reverse T4/T8 ratios (Louria,Hensle
& Rose, 1967, McDonough, Madden & Falek, 1980; Drew, Mills &
Levy, 1985; Creglev & Mark, 1986; Moss, 1987). All the psychoactive
drugs currently in use in this way, especially heroin and experimental
mixtures, are profoundly depressing to appetite, general health and immunity.
Cocaine and crack damage the respitory ephithelium which is a main barrier
to all airborne infections. Alternation of excitement and depression
leads quickly to habituation, overdosage and reckless disregard of alI
the personal and societal consequences of this life style.
Drug use has been escalating in conurbations in the USA for 25 years,
and is now the main reason for heterosexual spread of AIDS (Moss, 1987)
there and in many other countries. If infection is minimised by using uncontaminated
drugs and needles, or especially by opting for less toxic oral drugs such
as methadone, many addicts can live equably with their habit for many years
(Caper, Goldsmith & Stewart, 1972; Creglav & Mark, 1986). Otherwise,
chronic infection, especially with therapyresistant protozoa and fungi,
leads to severe disease in target organs and often to death. A pregnant
woman in this state transmits her infections and her drugtoxicity
congenitally to her child. In some countries, drug addicts donate blood
for payment and transmit their latent or active infections to plasma pools.
Most or all of the extending range of infections listed as indicators for
AIDS (Table 4) and other microflora from the local environment were perceived,
together with defects in immunity, in persons in these categories before
AIDS appeared. They now include multidrug resistant forms of tuberculosis.
The illegal use of drugs is also diversifying as a predictable but usually
uncontrollable disaster in large and growing sectors of youth and young
adults in the conurbations of the western world. HIV was wellestablished
in this population internationally by 1985, and is continuing to spread
Immune system activation
HIV differs from nonretroviral infections because of the affinity
between glycoprotein 120 on the surface of the virus and CD4 receptors
on Tcells. This facilitates entry of HIV into a minority of cells
and initiates a generalized immune response: activation of Tcells,
lymphadenopathy, antibodies to envelope proteins, antigenspecific
tolerance, neutralization of virus and latency of infection. The HIV hypothesis,
postulating reactivation of virus by internal regulation and destruction
of immunity by kill ing of Thelper lymphocytes is falsified by the
fact that immunity is sufficient to arrest replication of virus and delay
onset of further disease, in the absence of risk behaviour, by ten years
or more. The usual signal of advance of disease is not viral replication,
but a continuing fall in CD4 lymphocytes. In so far as it can occur in
other infections, in grafthost disease and in disordered immunity,
this is a largely nonspecific event. But it is a significant event
in AIDS because it is associated with the appearance of lymphocytotoxic
antibodies (LCTAs) acting against nonHLA antigens and peripheral blood
B and Tlymphocytes in some haemophiliac and homosexual patients
(Pruzanski, Jacobs & Laing, 1983; Kiprov, Anderson & Morand, 1985;
Ozturk, Koller & Horsburgh, 1987; Stricker, McHugh & Moody, 1987;
Daniel, Schimpf & Opelz, 1989). These occur in seronegative and seropositive
patients, but are much more prevalent in the latter and in homosexual and
haemophiliac patients with AIDS. They are crossreactive with major
histocompatibility (MHC) class II proteins on B and Tcells, with
spermatozoa! antigens (Ashida & Schofield, 1987; RootBernstein
& Hobbs, 1991) and with antigens from C.allhicans, the cause
of the orooesophageal infection which was and is a main and early
indicator for AIDS.
Male homosexuals have antispermatozoa! antibodies in the blood,
which crossreact with Tcells and have been linked to the occurrence
of azoospermia and testicular atrophy in homosexual men (Adams, DonovanBrand
& FriedmanKien, 1988; Ma & Armstrong, 1989). The same antibodies
have been detected in female patients with AIDS (Sheppard & Ascher,
1990) and are crossreactive with Tcells and HIV antibodies. The
common factor is obviously anal intercourse, a main riskfactor for
female as for male AIDS. These crossreactions reflect a mixed state
of allogenic and autoimmunity in which patients, with and without
HIV, reject their own Tcells because they cannot distinguish them
from antigens from spermato
zoa, HIV, other infections, foreign proteins and cells in transfusions
and in injection needles used for street drugs. This explains the selective
incidence of AIDS in homosexual men, in women with bisexual partners or
who engage in anal intercourse, and in haemophiliacs, some of whom would
be additionally at risk because of innate disorders of immune regulation
or of immunosuppression by drugs.
Sheppard and Ascher (1988, 1990, 1992) go further. They see the pathogenesis
of AIDS as the outcome of two sets of signals acting on Tcells in
a continuous process of immune activation. The first (specific) signal
comes from the interaction of a Tcell receptor with an antigenic peptide
presented as an MHC molecule following infection with HIV. The second signal
is nonspecific and is provided by selfmolecules on cells which react
with other Tcell receptors and regulate the activation produced by
the first. Most of the progeny of the activated cells ( lymphocytes and
thymocytes) are eliminated by 'programmed death' (apoptosis) which restores
the immune system to equilibrium (Zacharchuk, Mercep & Chakraborti,
1990), but a minority remain as 'memory' cells in a resting state in which
they retain their capacity to respond to an appropriate stimulus (Beverly,
1991). This may come in various ways: in HIV infection, from activation
of Tcells by interaction of gp l20 with CD4, leading to lymphadenopathy
and nonspecific autoimmune responses. The shift toward programmed
cell death then causes a fall in CD4 cells (McClure & Dalgleish, 1992).
But there is evidence also of antigen tolerance by clonal deletion of reactive
thymocytes and of Bcells of the spleen, by activity of superantigens
(Quarantino, Murison & Knyba, 1991) which act on VB regions of Tcell
receptors, and by what Sheppard and Ascher (1992) call a 'paradoxicallyintense
response' to peptides involved in alloreactivity. It is likely that
some of the many drugs used in the treatment of AIDS contribute to this.
The outcome depends also on the frequency of exposure to antigens and on
the ability of HIV quasispecies to induce the second signal.
One of the wellrecognised immunological anomalies in AIDS (Duesberg,
1989) is that HIV can only replicate in the antigenpresenting Tcells
which it suppresses. These cells multiply during the period of general
immune activation in the onset of infection, and accept the gpl20/CD4TCR
antigen complex (Dalgleish, Wilson & Gompels, 1992), after which they
decrease. This is restricted to subsets with MHC Class II allodeterminants
which mimic HIV1, supporting the likelihood that the response is autoimmune,
similar to that in graftvhost disease, in persons in VB subfamilies
with selective HLAassociated susceptibility to HIV1 (Fabio, Scorza
& Lazzarin, 1992). In a comprehensive investigation of the immunology,
RootBernstein suggests (1992, 1993) that this response is a multiple
antigenmediated autoimmunity (MAMA) provoked by the various infections,
drugs and alloantigens. These theories offer an explanation of the
mechanism of immune activation, but they do not explain the long periods
of latency which may follow.
The evidence from this active immunological front presents AIDS in many
patients as an autoimmune disease precipitated by rejection of Thelper
lymphocytes and thymocytes in complicated crossreactions with any
or all of several antigens, and in selfnonself discrimination (von
Boehmer & Kisielow, 1990; Sprent, Gao & Webb, 1990) in persons
in genetically susceptible subpopulations. This results in an upset
of immunological tolerance and a suppression of cellmediated immunity to
the point where it can no longer cope with additional infections. With
spermatozoa as alloantigens and drugs as independent immunosuppressants
included, and with the immunoreactive haplotypes in Caucasian populations
defined, this would seem to be sufficient to explain much, if not all,
of the pathogenesis as well as the selective and continuing incidence of
AIDS almost exclusively in subsets of populations in defined risk groups
in North America, Europe and Australasia.
The need for an alternative hypothesis
This has been raised on several occasions especially by Duesberg (1987,
1989), Sonnabend (1989), Evans (1989a) and by the author (1989, 1992a).
Sonnabend, working with patients in Manhattan, was the first to explain
the vunerability of homosexual men, in particular the effect of spermatozoa
in the rectum on immunity. He suggested that risk factors for seroconversion
are different from those for AIDS in which autoimmunisation, release of
interferon, massive inocula in tranfused blood and bloodproducts,
and a trigger effect of coincident viral infections might account for the
pathogenesis of ARCs and AIDS.
An alternative hypothesis must explain not only the pathogenesis of
immune deficiency in AIDS, but also the pattern of transmission and epidemiology.
In the hypothesis presented here, AIDS is presented as a disease acquired
in the first place by selfpreferred or imposed behaviours, which in
themselves dysregulate immunity and homeostasis while also leading to exposure
to various pathogenic and opportunistic infections. The complex syndrome
which follows has infectious, immunological and metabolic features. The
hypothesis rejects HIV as a unique and sufficient cause of all this but
agrees that it is transmissible in sexual secretions and blood, causing
HIV disease: lymphadenopathy and febrile illness followed by latency or
minimal pathological change during which there is evidence of direct celltocell
transmission of virus to migrant mononuclears and neural cells, of direct
encephalopathy and of immune activation.
AIDS and AIDSrelated complexes (ARCs) develop, with and without
HIV, because heterologous antigens in spermatozoa enter the rectum and
bloodstream, or in whole blood and blood concentrates given as transfusions,
provoke allogenic responses and elicit antibodies which are toxic to lymphocytes,
and cause a fall in CD4 counts. HIV can do the same by joining with CD4
receptors on Thelper lymphocytes presented along with MHC Class II
proteins because of molecular affinities. This complex is tolerated, because
it is recognisable at first as self, so HIV survives in clones of activated
lymphocytes and monocytes in the presence of neutralising antibodies. But
repeated infections of the genital, alimentary and respiratory tracts conveyed
with various heterologous antigens, as above, maintain the Tcell activation
while antilymphocyte antibodies are being formed. This leads to autoimmunity
with a fall in CD4 count, reversal of the T4/T8 ratio, energy and programmed
cell death of T and Blymphocytes, consistent with the collapse
of immunity, and atrophy of thymic and splenic follicles found postmortem
in patients dying with AIDS. It explains the general absence of AIDS in
immunocompetent persons, the special susceptibility of homosexual men and
haemophiliacs, and the risk to the foetus of a mother with AIDS; and it
is entirely consistent with the epidemiological pattern of AIDS in the
USA and most of Europe to date.
The occurrence of AIDS in drug users is attributable, firstly, to the
general immunosuppressive properties of most of the major psychoactive
drugs at present in use and secondly, to contaminants and impurities which
cause refractory infections and dysregulate immunity. Persons in this risk
category often overlap with the male homosexual group. Girls and women
place themselves at high risk by taking drugs or by having intercourse
with men in high risk groups. If they are pregnant, their infants share
these risks by intrauterine or perinatal exposure. Otherwise, the
spread of AIDS by heterosexual transmission in either direction is minimal
or absent except in subSaharan Africa where registrations are increasing
rapidly, but in a totally different clinical and epidemiological pattern
which overlaps with other, prevalent infections and with malnutrition.
Predictions made on this basis are accurate to within 10% of registered
totals of current and cumulative incidence in the USA and UK. The riskbehaviour
hypothesis postulates that, for these reasons, AIDS will continue to occur
in persons and communities in defined susceptibility groups although HIV
disease will be much more widely prevalent. Along with other organisms
(HSV, CMV, VZ, EBV, various protozoa, fungi and bacteria), HIV can be activated
from latency by various forms of risk behaviour, as described above, because
this leads to an overload of genital, alimentary, pulmonary and systemic
infections compounded by dysregulation of natural immunity, either by spermatozoa
in the rectum and blood in persons of either sex experiencing traumatic
anal intercourse, or from organisms acquired in oral sex, or from the immunotoxic
effects of injected or ingested drugs or from selfmedication by broadspectrum
antimicrobial agents or, frequently, from al1 of these in lifestyles
which disregard elementary rules of hygiene and nutrition. In persons
choosing these lifestyles, AIDS is essentially a selfinflicted
disease which can only be prevented by awareness and selfcontrol.
For persons upon whom these risks are inflicted, one way or another, it
is becoming increasingly and tragically obvious that protection is imperative.
Impact of this new hypothesis on research and control of AIDS
The monopolistic hypothesis that HIV I is the unique cause of AIDS
has, since 1984, led not only to erroneous predictions, but also to widespread
misinformation and grotesque errors in prognosis, treatment, allocation
of resources and strategy for research (Rubin, 1988; Adams, 1988; Eigen,
1989; Stewart, 1989, 1992a; Craven, Stewart & Taghavi, 1994). Resources
and funds for the longer term are allocated mainly for singlefactor
strategy based on the false assumptions (Montagnier, 1994) that a specific
vaccine or drug will eliminate or cure AIDS. Even if this were possible,
the ethical and logistic problems would be immense. To whom would the vaccine
be given? Would recipients be encouraged to continue riskbehaviour?
How else would exposure and efficacy be measured? Or will the vaccine or
vaccines be used as shotguns on the blind guess that everyone is already
at risk? Since heterosexual spread is not occurring in developed countries
on anything approaching the scale envisaged in official predictions, it
is easy to see how a vaccine used widely at this stage could be given credit
for control of a pandemic which is not occurring. On the drug front, the
consensus jumped the gun by promoting the use of Azidothymidine (AZT, Zidovudine),
a highly cytotoxic drug, for prophylaxis in seropositive pregnant women
and infants on the assumption that without it, they would all develop AIDS
and die. This policy continues, despite the evidence in the prolonged AngloFrench
Trial (Aboulker & Swart, 1993; Concorde,1994) which showed no significant
prophylactic effect in symptomfree HIVpositive subjects in terms
of survival or disease progression after five years.
If the HIV hypothesis is inadequate or wrong, the risks and misplacement
of effort and research since 1984 will be enormous. The alternative hypothesis
offered here differentiates HIV infection and disease from AIDS which,
in developed countries at least, is a complex amalgam of diseases determined
first and foremost by high risk behaviour in subsets of populations in
restricted social, ethnic and geographic locations. It postulates that
prevention depends essentially upon recognition and control of these existential
determinants by education, notification, contact tracing and, if necessary,
by legal constraints upon behaviour which places unaware or passive persons,
including unborn infants, at equally high or higher risks. The situation
in the developing world is even more serious but is different in ways which
cannot be understood without a more informative database about the
distribution and pattern of AIDS and other lifethreatening and sexuallytransmitted
diseases, and about life styles in affected countries.
The data and predictions supporting the alternative riskbehaviour
hypothesis are presented here in a manner which opens them in the short
term to falsification and correction, for instance, by factual data excluding
other diagnoses and confirming the occurrence of destruction of immunity
with unremitting signs of AIDS and HIviraemia by secondary transmissions
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