A randomized study of antiviral medication switch at lower- versus higher-switch thresholds: AIDS Clinical Trials Group Study A5115.

TitleA randomized study of antiviral medication switch at lower- versus higher-switch thresholds: AIDS Clinical Trials Group Study A5115.
Publication TypeJournal Article
Year of Publication2007
AuthorsRiddler SA, Jiang H, Tenorio A, Huang H, Kuritzkes DR, Acosta EP, Landay A, Bastow B, Haas DW, Tashima KT, Jain MK, Deeks SG, Bartlett JA
JournalAntivir Ther
Volume12
Issue4
Pagination531-41
Date Published2007
ISSN1359-6535
KeywordsAdult, Anti-HIV Agents, Antigens, CD38, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes, Drug Administration Schedule, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Pilot Projects, Reverse Transcriptase Inhibitors, RNA, Viral, Treatment Outcome, Viremia
Abstract

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.

Alternate JournalAntivir. Ther. (Lond.)
PubMed ID17668562
Grant ListAI 069439 / AI / NIAID NIH HHS / United States
AI 136156 / AI / NIAID NIH HHS / United States
AI 25868 / AI / NIAID NIH HHS / United States
AI 25915 / AI / NIAID NIH HHS / United States
AI 27659 / AI / NIAID NIH HHS / United States
AI 27663 / AI / NIAID NIH HHS / United States
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AI 27675 / AI / NIAID NIH HHS / United States
AI 28858 / AI / NIAID NIH HHS / United States
AI 32770 / AI / NIAID NIH HHS / United States
AI 32775 / AI / NIAID NIH HHS / United States
AI 32782 / 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 39156 / AI / NIAID NIH HHS / United States
AI 46376 / AI / NIAID NIH HHS / United States
AI 46381 / AI / NIAID NIH HHS / United States
AI 46383 / AI / NIAID NIH HHS / United States
AI 50410 / AI / NIAID NIH HHS / United States
K24 AI01744 / AI / NIAID NIH HHS / United States
K24 RR16482 / RR / NCRR NIH HHS / United States
P30 AI 60354 / AI / NIAID NIH HHS / United States
P30 AI64518 / AI / NIAID NIH HHS / United States
RR 00046 / RR / NCRR NIH HHS / United States
RR 00051 / RR / NCRR NIH HHS / United States
U01 AI 38858 / AI / NIAID NIH HHS / United States
U01 AI27659 / AI / NIAID NIH HHS / United States