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

TitleA randomized trial of treatment interruption before optimized antiretroviral therapy for persons with drug-resistant HIV: 48-week virologic results of ACTG A5086.
Publication TypeJournal Article
Year of Publication2006
AuthorsBenson CA, Vaida F, Havlir DV, Downey GF, Lederman MM, Gulick RM, Glesby MJ, Wantman M, Bixby CJ, Rinehart AR, Snyder S, Wang R, Patel S, Mellors JW
Corporate AuthorsACTG A5086 Study Team
JournalJ Infect Dis
Volume194
Issue9
Pagination1309-18
Date Published2006 Nov 1
ISSN0022-1899
KeywordsAdult, Anti-HIV Agents, Drug Administration Schedule, Drug Resistance, Multiple, Viral, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Phylogeny, Time Factors
Abstract

BACKGROUND: The role of structured treatment interruption (STI) before optimized antiretroviral therapy (ART) in patients with drug-resistant human immunodeficiency virus type 1 (HIV-1) 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-1 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 wild-type 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 classes.

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 3-drug class resistance on the same genome.

DOI10.1086/508289
Alternate JournalJ. Infect. Dis.
PubMed ID17041858
Grant ListAI 25859 / AI / NIAID NIH HHS / United States
AI 25879 / AI / NIAID NIH HHS / United States
AI 25897 / AI / NIAID NIH HHS / United States
AI 27660 / AI / NIAID NIH HHS / United States
AI 27663 / AI / NIAID NIH HHS / United States
AI 27665 / AI / NIAID NIH HHS / United States
AI 27670 / AI / NIAID NIH HHS / United States
AI 32770 / AI / NIAID NIH HHS / United States
AI 32775 / AI / NIAID NIH HHS / United States
AI 34832 / AI / NIAID NIH HHS / United States
AI 34853 / AI / NIAID NIH HHS / United States
AI 38855 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI 46339 / AI / NIAID NIH HHS / United States
AI 46370 / AI / NIAID NIH HHS / United States
AI 46383 / AI / NIAID NIH HHS / United States
AI 46386 / AI / NIAID NIH HHS / United States
AI 51951 / AI / NIAID NIH HHS / United States
AI 51966 / AI / NIAID NIH HHS / United States
P30-AI 27767 / AI / NIAID NIH HHS / United States
RR 00032 / RR / NCRR NIH HHS / United States
RR 00051 / RR / NCRR NIH HHS / United States
RR 00096 / RR / NCRR NIH HHS / United States
RR 0047 / RR / NCRR NIH HHS / United States