AZT TRIAL IN ASYMPTOMATIC HIV-POSITIVE PATIENTS IS UNDERWAY AT NIAID's ATEUs; CHEMOPROPHYLAXIS SEEN AS BEST CURRENT APPROACH TO AIDS DRUG DEVELOPMENT

Executive Summary

AZT trials on asymptomatic HIV-positive individuals are currently getting underway, National Institute of Allergy & Infectious Diseases (NIAID) Director Anthony Fauci, MD, said at an Aug. 31-Sept. 1 conference on AIDS drug development sponsored by the National Academy of Sciences' Institute of Medicine. As of Aug. 21, 163 asymptomatic seropositive patients have been enrolled into the trials. The eventual target population is 1,600. The trials will be conducted in all 19 of NIAID's AIDS Treatment Evaluation Units. The objective of the study is to ask "whether or not the administration in an appropriate dose chronically to a seropositive asymptomatic individual will in fact block the progression . . . onto symptomatic disease, be that ARC or AIDS," Fauci said. The trial will be a three-year randomized, double-blind and placebo controlled study. The 1,600 patients will be divided into three groups, one group will receive 300 mg of AZT, another 100 mg of AZT and the third will receive a placebo, NIAID stated. The dosing regimen for each group will be the substance given every four hours, five doses a day. NIAID said that with AZT it hopes to see a delay in the development of ARC, a determination of the antiviral effects, a decrease in the frequency of and the prolongation in the time to acquisition of AIDS opportunistic infection and restoration of immune response. The AZT trial to see if the drug can prevent progression to disease in asymptomatic HIV infected individuals is an example of research on prevention of AIDS through chemotherapeutic intervention, an approach which several speakers at the conference said is the most promising current approach. For example, William Haseltine, Dana-Farber Cancer Center, said that because prevention of AIDS by a vaccine appears to be a long-range objective, the answer may be in long-term chemoprophylaxis for high-risk individuals. Haseltine stated that since "the AIDS virus is designed to evade immune response, it may be difficult to make an AIDS vaccine, therefore chemoprophylaxis for prevention" should be investigated. Other researchers voiced their doubts about the effectiveness of an AIDS vaccine and agreed that the prevention of virus replication and progression to disease should be the approach in the development of AIDS drugs. Chemoprophylaxis, Haseltine continued, would be for "those who are at extremely high risk, the sex partners of people who are known to be infected or perhaps a situation such as in Central Africa, where we can expect in some cities perhaps five and perhaps as much as 10% of the total sexually active population may become infected within . . . two or three years." The goal for the successful chemical treatment of AIDS is "by the combination of antiviral drugs that act synergistically to inhibit virus replication with minimal toxic, teratogenic, and carcinogenic side effects," Haseltine concluded. In listing AIDS drugs that are under development at NIH, Fauci mentioned some recently discovered agents: CS87- 3'azido 2' 3'dideoxyuridine, D4T-2'3' dideoxy 2'3'didehydrothymidine and D4C- 2'3' dideoxy 2'3'didehydrocytidine. These analogs of DDC are being developed by an NIAID-sponsored National Cooperative Drug Discovery Group at Emory University, which is headed by the principal investigator Andre Nahmias.