A randomized study of antiviral medication switch at lower- versus higher-switch thresholds: AIDS Clinical Trials Group Study A5115.
BACKGROUND
Clinical stability has been observed with continued antiretroviral therapy (ART) in the setting of partial virological suppression. The optimal time to switch treatment in patients with low but detectable HIV-1 RNA is not known.


METHODS
Subjects on stable ART with HIV-1 RNA 200-10,000 copies/ml were randomized to an immediate treatment switch, or to a delayed switch when HIV-1 RNA increased to > or = 10,000 copies/ml or CD4+ T-cell count decreased by 20%. The primary outcome measures were immune activation (proportion of CD8+ T-cells expressing CD38 at week 48) and evolution of genotypic drug resistance.


RESULTS
The study failed to fully accrue the originally planned 108 subjects. Only 47 subjects were randomized to immediate- or delayed-switch arms. Of the subjects in the delayed-switch arm, 10/23 (43%) met the criteria for ART switch during the study (median follow-up 82 weeks). After 48 weeks of observation, the level of immune activation was comparable in the two arms. New resistance mutations were observed in 3/17 and 8/19 subjects in the immediate- and delayed-switch groups, respectively. The loss of future treatment options, however, was comparable in the delayed- and immediate-switch groups.


CONCLUSIONS
Individuals with partial viral suppression tend to remain immunologically stable, however, the accumulation of drug resistance mutations is an ongoing risk. Delayed switch in ART may be a reasonable short-term strategy for individuals with very limited treatment options.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. riddler@dom.pitt.edu
Sharon A
SA
Riddler
Hongyu
H
Jiang
Allan
A
Tenorio
Hairong
H
Huang
Daniel R
DR
Kuritzkes
Edward P
EP
Acosta
Alan
A
Landay
Barbara
B
Bastow
David W
DW
Haas
Karen T
KT
Tashima
Mamta K
MK
Jain
Steven G
SG
Deeks
John A
JA
Bartlett
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D051997:ADP-ribosyl Cyclase 1