The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a selective inhibition of viral reverse transcriptase, thereby preventing the formation of new proviral DNA in permissive, uninfected cells. Given that initial HIV infection of an individual instigates abundant HIV replication from inception until death, and that the life of infected T-cells is only several days, the administration of AZT should lead both in vitro and in vivo (i) to decreased formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV isolation' (detection of p24 or reverse transcription or both) in stimulated cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load') ultimately resulting in low or absent levels of all three parameters; and (iv) to a perfect and direct correlation between all these parameters. A critical analysis of the presently available data shows that no such evidence exists, an outcome not unexpected given the pharmacological data on AZT. HIV experts all agree that only the triphosphorylated form of AZT (AZTTP) and not the unphosphorylated form administered to patients, nor its mono- or diphosphate, is the active agent. Furthermore, the mechanism of action is the ability of AZTTP to halt the formation of HIV-DNA (chain termination). However, although this claim was posited from the outset, AZT underwent clinical trials and was introduced as a specific anti-HIV drug many years before there were any data proving that the cells of patients are able to triphosphorylate the parent compound to a level considered sufficient for its putative pharmacological action. Notwithstanding, from the evidence published since 1991 it has become apparent that no such phosphorylation takes place and thus AZT cannot possess an anti-HIV effect. However, the scientific literature does elucidate: (i) a number of biochemical mechanisms which predicate the likelihood of widespread, serious toxicity from use of this drug; (ii) in vitro data proving that AZT has significant antibacterial and antiviral properties which confound interpretation of its effects when administered to patients. Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.
Seventy patients were investigated by isotope venography of the lower leg veigns and pelvis using 99Tcm human serum albumin, mainly as microspheres, in the course of routine lung scanning. In 54 of these patients, 52 pelvic, and 98 conventional ascending X-ray contrast venograms were performed for comparison, ninety three per cent showed good correlation, and 4% poor correlation. There were 2% false positive and 1% false negative isotope examinations. Isotope venography proved to be a painless, safe and reliable method for the detection of deep vein thrombosis. Its correlation with contrast venography is high, especially for the upper thigh and pelvis. It can be performed in 30 minutes, including standard lung scan, and can be repeated in patients to assess response to treatment, saving the patient the discomfort and radiation of comparable radiological examinations.
The existence of specific antibody/protein reactions is the crucial assumption underlying proof of HIV isolation, proof of HIV infection and the causative role of HIV in AIDS. However, since 1. antibodies which react with the 'HIV' proteins arise following allogenic stimuli in non-HIV-infected animals and humans, as well as in mice and humans with autoimmune disorders; antibodies to antigens from both mycobacteria and yeasts cross-react with HIV env and gag proteins; 2. individuals belonging to the AIDS risk groups are subjected to allogenic stimuli and have high levels of autoimmune antibodies, while the vast majority of patients in the AIDS risk groups are infected with either or both mycobacteria or yeasts; the evidence for the existence of HIV and its putative role in AIDS must be reappraised.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.