A randomized trial of treatment interruption before optimized antiretroviral therapy for persons with drug-resistant HIV: 48-Week virologic results of ACTG A5086

Background. The role of structured treatment interruption (STI) before optimized antiretroviral therapy (ART) in patients with drug-resistant human immunodeficiency virus type I (HIV-I) is uncertain. Methods. AIDS Clinical Trial Group protocol A5086 was a prospective trial of 41 patients with multiple drug class-resistant HIV who were randomized to undergo a 16-week STI followed by optimized ART (STI) or immediate optimized ART (no STI). The primary end point was the proportion of subjects with HIV-1 RNA loads < 400 copies/mL 48 weeks after randomization. Results. Of 39 evaluable patients, 4 (19%) in the STI arm and 6 (33%) in the no STI arm had HIV-I RNA loads < 400 copies/mL at 48 weeks (P = .44). Median changes from baseline in CD4(+) cell counts and HIV-1 RNA loads were similar for both arms. Standard genotypes at the end of STI showed nearly complete reversion to wildtype virus in a minority of patients (n = 5; 28%). Virus with 3-drug class resistance reemerged even when ART included only 1 or 2 drug classes. Single-genome sequencing showed that each genome encoded resistance mutations for 3 drug casses. Conclusions. A 16-week STI before optimized ART did not improve virologic response. Genetic analyses strongly, suggest that virologic failure resulted from the reemergence of virus present before STI that encoded 30, drug class resistance on the same genome.