L-697,661, a pyridinone, is a potent inhibitor of HIV-1 reverse transcriptase that is limited by the rapid development of viral resistance. The purpose of this study is to determine if co-administering ZDV with L-697,661 delays the development of viral resistance. 27 of 35 patients with advanced HIV infection have been enrolled into this randomized, double-blind, 24 week study comparing L- 697,661 (400 mg q 8h) plus ZDV (200 mg q 8h) to ZDV alone (200 mg q 8h). Patients range in age from 26 to 53 years, with a median age of 38 years. All are male: 23 Caucasians, 3 African Americans, and 1 Asian. The mean CD4 count at entry was 99 cells/mm3. Circulating p24 antigen was detected in 10 of 27 patients (37%) prior to therapy. Patients are being monitored for toxicity and clinical events. Efficacy will be assessed by changes in CD4 counts, p24 antigen levels, and serum viral RNA levels using quantitative PCR. Samples will also be tested for the development of viral resistance using phenotypic and genotypic assays. After an average of 10 weeks on study, relatively few adverse clinical experiences have been observed: mild serum transaminase elevation (less than 2 x nl) (13 pts), neutropenia (less than 750 ANC) (5 pts), mild headache (7 pts), nausea (4 pts), pruritus and skin rash (2 pts). Clinical, immunologic and virologic response data will be presented.

Cohort Studies CD4 Lymphocyte Count Human HIV Infections/*DRUG THERAPY Zidovudine/*THERAPEUTIC USE ABSTRACT

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