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 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.
Benson
Constance A
CA
University of California, San Diego School of Medicine, San Diego, CA 92103, USA. cbenson@ucsd.edu
Vaida
Florin
F
Havlir
Diane V
DV
Downey
Gerald F
GF
Lederman
Michael M
MM
Gulick
Roy M
RM
Glesby
Marshall J
MJ
Wantman
Michael
M
Bixby
Christian J
CJ
Rinehart
Alex R
AR
Snyder
Sally
S
Wang
Rui
R
Patel
Sheran
S
Mellors
John W
JW
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D013997:Time Factors
D019380:Anti-HIV Agents