Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial.

TitleComparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial.
Publication TypeJournal Article
Year of Publication2010
AuthorsFlexner C, Tierney C, Gross R, Andrade A, Lalama C, Eshleman SH, Aberg J, Sanne I, Parsons T, Kashuba A, Rosenkranz SL, Kmack A, Ferguson E, Dehlinger M, Mildvan D
Corporate AuthorsACTG A5073 Study Team
JournalClin Infect Dis
Volume50
Issue7
Pagination1041-52
Date Published2010 Apr 1
ISSN1537-6591
KeywordsAnti-Retroviral Agents, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV, HIV Infections, Humans, Lopinavir, Male, Proportional Hazards Models, Pyrimidinones, Ritonavir, RNA, Viral, Treatment Outcome, Viral Load
Abstract

BACKGROUND: Dosing frequency is an important determinant of regimen effectiveness. Methods. To compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral therapy, we randomized human immunodeficiency virus (HIV)-positive, treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage of 400 mg of lopinavir and 100 mg of ritonavir BID (n = 160) or 800 mg of lopinavir and 200 mg of ritonavir QD (n = 161), plus either emtricitabine 200 mg QD and extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of 300 mg QD. Randomization was stratified by screening HIV RNA level <100,000 copies/mL versus > or = 100,000 copies/mL. The primary efficacy end point was sustained virologic response (SVR; defined as reaching and maintaining an HIV RNA level <200 copies/mL) through week 48.

RESULTS: Subjects were 78% male, 33% Hispanic, and 34% black. A total of 82% of subjects completed the study, and 71% continued to receive the initially assigned dosage schedule. The probability of SVR did not differ significantly for the BID versus QD comparison, with an absolute proportional difference of 0.03 (95% confidence interval [CI], -0.07 to 0.12). The comparison depended on the screening RNA stratum (P=.038); in the higher RNA stratum, the probability of SVR was significantly better in the BID arm than in the QD arm: 0.89 (95% CI, 0.79-0.94) versus 0.76 (95% CI, 0.64-0.84), a difference of 0.13 (95% CI, 0.01-0.25). Lopinavir trough plasma concentrations were higher with BID dosing. Adherence to prescribed doses of LPV/r was 90.6% in the QD arm versus 79.9% in the BID arm (P<.001). Conclusions. Although subjects assigned to QD regimens had better adherence, overall treatment outcomes were similar in the QD and BID arms. Subjects with HIV RNA levels > or =100,000 copies/mL had better SVR with BID regimens at 48 weeks, which suggests a possible advantage in this setting for more frequent dosing. Clinical trial registration. ClinicalTrials.gov registration number: NCT00036452.

DOI10.1086/651118
Alternate JournalClin. Infect. Dis.
PubMed ID20192725
PubMed Central IDPMC2833234
Grant ListAA54907 / AA / NIAAA NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
U01 AI069423 / AI / NIAID NIH HHS / United States
U01 AI069465 / AI / NIAID NIH HHS / United States
U01 AI069465-04 / AI / NIAID NIH HHS / United States
U01 AI68636 / AI / NIAID NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
UL1 RR025005-03 / RR / NCRR NIH HHS / United States