Journal Article

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

Charles Flexner, Camlin Tierney, Robert Gross, Adriana Andrade, Christina Lalama, Susan H. Eshleman, Judith Aberg, Ian Sanne, Teresa Parsons, Angela Kashuba, Susan L. Rosenkranz, Anne Kmack, Elaine Ferguson, Marjorie Dehlinger and Donna Mildvan

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 7, pages 1041-1052
Published in print April 2010 | ISSN: 1058-4838
Published online April 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/651118
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

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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 ⩾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 ⩾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.

Journal Article.  6402 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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