Epidemiology of AIDS- 1

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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 grounds.
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.

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.

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.

Conclusion
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 to and between persons not engaging in risk­behaviour, or in infants of seropositive mothers not exposed to direct or indirect risks.