David Causer

A critical analysis of the HIV-T4-cell-AIDS hypothesis.

The data generally accepted as proving the HIV theory of AIDS, HIV cytopathy, destruction of T4 lymphocytes, and the relationship between T4 cells, HIV and the acquired immune deficiency clinical syndrome are critically evaluated. It is concluded these data do not prove that HIV preferentially destroys T4 cells or has any cytopathic effects, nor do they demonstrate that T4 cells are preferentially destroyed in AIDS patients, or that T4 cell destruction and HIV are either necessary or sufficient prerequisites for the development of the clinical syndrome.

FACTOR VIII, HIV AND AIDS IN HAEMOPHILIACS: AN ANALYSIS OF THEIR RELATIONSHIP

In this review, the association between the Acquired Immune Deficiency Syndrome (AIDS) and haemophilia has been carefully examined, especially the data that have been interpreted as indicating transmission of the human immunodeficiency virus (HIV) to the recipients of purportedly contaminated factor VIII preparations. In our view, the published data do not prove the hypothesis that such transmission occurs, and therefore HIV cannot account for AIDS in haemophiliacs.

High rates of HIV seropositivity in Africa--alternative explanation.

Although to some it may seem `curious indeed’ a non-retroviral explanation for the correlation between `seropositivity’ and morbidity mortality and AIDS in Africa is eminently possible. Clinical practitioners are no strangers to tests of significant utility and predictive ability which are nonetheless devoid of specificity. Arguably the test which provides the best example is the erythrocyte sedimentation rate (ESR) because it like the HIV antibody tests is associated with elevations of antibodies and acute phase reactant proteins. Indeed there is evidence that an elevated ESR is a superior predictive marker for the development of clinical AIDS than is a decrease in the CD4 cell count although the latter is said to be the cause of the syndrome. A positive antibody test like the ESR may indicate a propensity to the development of particular diseases without necessarily being linked to HIV infection. (excerpt)

HIV Antibody Tests and Viral Load - More Unanswered Questions and A Further Plea for Clarification: Short Communication

SummaryAt present, it is accepted that in 1983 Montagnier proved the existence of HIV. In their 1983 study, Montagnier and his colleagues took the supernatant from cultures containing tissue derived from AIDS patients and banded it in sucrose density gradients. They claimed that the 1.16g/ml band represented purified virus 1. Some of the proteins and RNAs were considered to represent the retroviral proteins and retroviral genome, respectively. Subsequently the proteins were used as antigens for the antibody tests, and the nucleic acids for hybridisation and PCR studies. Indeed, it is logical that if the 1.16 g/ml band contained purified viral-like particles and the particles were infectious, one has no choice but to consider both the proteins and the RNA as being viral constituents.

Questions about Results Reported with Potent Antiretroviral Therapy for Human Immunodeficiency Virus Type 1 Infection

To the Editor—Thackray and Field [1] raise 4 points that they believe explain why our recent study [2] failed to document the virologic superiority of famciclovir over valacyclovir that they described in several reports and numerous abstracts. First, the route of infection did differ, as we acknowledged in our Discussion section [2]. They argue, however, that infection of the cornea (as opposed to the ear pinna in their model system) would favor direct uptake of virus into the axons, eliminating the opportunity a drug started 24 h later might have to limit viral amplification in the ganglia. We believe that any such aspect of our model system is overstated. In our studies, virus titers in tissues continued to rise for some days after the start of treatment (figure 3 in [2]). Thus, there remained ample opportunity for viral replication to be affected by the drugs. Nonetheless, we failed to observe any differential benefit of famciclovir. Moreover, Thackray and colleagues [3–5] reported experiments in which they delayed treatment even further and still observed superiority of famciclovir. Second, Thackray and Field [1] are concerned about the virus inoculum that we used, because it was associated with universal mortality in the absence of treatment. It is true that no positive controls remained with which to compare the effects of treatment on latency and reactivation; however, untreated animals survived long enough for us to observe that famciclovir and valacyclovir were equivalent in virologic outcome measures of the acute infection. Third, with regard to a rebound of virus titers, we disagree that there is a “variance with the results published” [1]. It has been our experience that the time points chosen are more than sufficient to track the spread of herpes simplex virus (HSV) from the eye to the trigeminal ganglia and into the brain. With the chosen time points, we saw the spread of virus through these tissues. Moreover, we detected no differences in the effect of either drug during the testing period. Obviously, for a true rebound to occur, the initial infection first must be cleared. Clearance was beginning to occur by the final time point, postinfection day 11. In an immunosuppression model, Field et al. [3] tested ear and brain samples on intermittent days and still detected a rebound of virus titers. Fourth, we claimed equivalence of both drugs in “terminating ganglionic infection” [2], by which we meant the presence of infectious virus in the tissue. Despite their claim to the contrary, Thackray and Field [4, 5] reported that famciclovir was superior in reducing the amount of both infectious and latent virus in ganglia and in “preventing the establishment of latency” (Discussion in [4]; Introduction and Discussion in [5]). We agree that each animal model has its own advantages and disadvantages. We believe, from our own data, that famciclovir and valacyclovir are equivalent for the acute treatment of HSV infections and will continue to believe so until a welldesigned clinical trial proves otherwise.