Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262).

TitleEfficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262).
Publication TypeJournal Article
Year of Publication2011
AuthorsTaiwo B, Zheng L, Gallien S, Matining RM, Kuritzkes DR, Wilson CC, Berzins BI, Acosta EP, Bastow B, Kim PS, Eron JJ
Corporate AuthorsACTG A5262 Team
JournalAIDS
Volume25
Issue17
Pagination2113-22
Date Published2011 Nov 13
ISSN1473-5571
KeywordsAdolescent, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Darunavir, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Medication Adherence, Middle Aged, Odds Ratio, Pyrrolidinones, Raltegravir Potassium, Ritonavir, RNA, Viral, Sulfonamides, Treatment Outcome, Viral Load, Young Adult
Abstract

OBJECTIVE: To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL) combination therapy in antiretroviral-naive patients.

DESIGN: Phase IIb, single-arm, open-label, multicenter study.

METHODS: One hundred and twelve antiretroviral-naive, HIV-1-infected patients received DRV/r 800/100 mg once daily and RAL 400 mg twice daily. Primary endpoint was virologic failure by week 24. Virologic failure was defined as confirmed viral load of 1000 copies/ml or more at week 12, or an increase of more than 0.5 log(10) copies/ml in viral load from week 4 to 12, or a confirmed viral load of more than 50 copies/ml at or after week 24. Protease and integrase genes were sequenced in patients experiencing virologic failure.

RESULTS: Virologic failure rate was 16% [95% confidence interval (CI) 10-24] by week 24 and 26% (95% CI 19-36) by week 48 in an intent-to-treat analysis. Viral load at virologic failure was 51-200 copies/ml in 17/28 failures. Adjusting for age and sex, virologic failure was associated with baseline viral load of more than 100,000 copies/ml [hazard ratio 3.76, 95% CI (1.52-9.31), P = 0.004] and lower CD4 cell count [0.77 per 100 cells/μl increase (95% CI 0.61-0.98), P = 0.037]. When trough RAL concentrations were included as a time-varying covariate in the analysis, virologic failure remained associated with baseline viral load more than 100,000 copies/ml [hazard ratio = 4.67 (95% CI 1.93-11.25), P < 0.001], whereas RAL level below detection limit in plasma at one or more previous visits was associated with increased hazard [hazard ratio = 3.42 (95% CI 1.41-8.26), P = 0.006]. All five participants with integrase mutations during virologic failure had baseline viral load more than 100,000 copies/ml.

CONCLUSION: DRV/r plus RAL was effective and well tolerated in most patients, but virologic failure and integrase resistance were common, particularly in patients with baseline viral load more than 100,000 copies/ml.

DOI10.1097/QAD.0b013e32834bbaa9
Alternate JournalAIDS
PubMed ID21857490
PubMed Central IDPMC3515052
Grant List1 UO1 AI 069494-01 / AI / NIAID NIH HHS / United States
1U01AI069503 / AI / NIAID NIH HHS / United States
1U01AI069513 / AI / NIAID NIH HHS / United States
5-U01 AI069423 / AI / NIAID NIH HHS / United States
5U01 AI069484 / AI / NIAID NIH HHS / United States
5U01AI069494 / AI / NIAID NIH HHS / United States
5UO1 AI069502 / AI / NIAID NIH HHS / United States
AI 069495 / AI / NIAID NIH HHS / United States
AI 69432 / AI / NIAID NIH HHS / United States
AI-069439 / AI / NIAID NIH HHS / United States
AI-069501 / AI / NIAID NIH HHS / United States
AI069471 / AI / NIAID NIH HHS / United States
AI069474 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
AI69501 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30-AI-045008-12 / AI / NIAID NIH HHS / United States
RR-024975 / RR / NCRR NIH HHS / United States
U01 AI027665 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069423 / AI / NIAID NIH HHS / United States
U01 AI069452 / AI / NIAID NIH HHS / United States
U01 AI069452 / AI / NIAID NIH HHS / United States
U01 AI069467 / AI / NIAID NIH HHS / United States
U01 AI069471 / AI / NIAID NIH HHS / United States
U01 AI069472 / AI / NIAID NIH HHS / United States
U01 AI069472-05 / AI / NIAID NIH HHS / United States
U01 AI069494 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
U01 AI069502 / AI / NIAID NIH HHS / United States
U01-AI-69467-05 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI069511-02 / AI / NIAID NIH HHS / United States
U01AI68634 / AI / NIAID NIH HHS / United States
UL 1RR 025747 / RR / NCRR NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 RR024989 / RR / NCRR NIH HHS / United States
UL1RR 024160 / RR / NCRR NIH HHS / United States