TY - JOUR
T1 - Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatmentNaive patients
T2 - Results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial
AU - Flexner, Charles
AU - Tierney, Camlin
AU - Gross, Robert
AU - Andrade, Adriana
AU - Lalama, Christina
AU - Eshleman, Susan H.
AU - Aberg, Judith
AU - Sanne, Ian
AU - Parsons, Teresa
AU - Kashuba, Angela
AU - Rosenkranz, Susan L.
AU - Kmack, Anne
AU - Ferguson, Elaine
AU - Dehlinger, Marjorie
AU - Mildvan, Donna
N1 - Funding Information:
Potential conflicts of interest. C.F. reports receiving grant support from Boehringer-Ingelheim and GlaxoSmithKline for research unrelated to this study; has served as a consultant to Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Roche, Schering-Plough, and Tibotec; and has received honoraria for presentations at meetings sponsored in part by Abbott Laboratories. C.T. reports serving as a member of a DSMB for Tibotec. R.G. reports receiving grant support from Bristol-Myers Squibb and Abbott for research unrelated to this study. A.A. reports receiving grant support from GlaxoSmithKline for research unrelated to this study and has served on an advisory board for Abbott. S.H.E. is a member of the clinical advisory board of Monogram Biosciences (formerly ViroLogic). J.A. has served on advisory boards for Gilead, Tibotec, Roche, Bristol-Myers Squibb, Pfizer, and Merck and has received research grants from Gilead, Tibotec, Roche, Pfizer, Merck, and Schering-Plough for research unrelated to this study. I.S. has served on advisory boards for Glaxo- SmithKline, Bristol-Myers Squibb, Pfizer, and Triangle Pharmaceuticals. A.K. reports receiving grant support from Tibotec, Gilead, Merck, Abbott, and Pfizer for research unrelated to this study and has served as a consultant to Bristol-Myers Squibb and Boehringer-Ingelheim. D.M. reports receiving grant support from Abbott, Bristol-Myers Squibb, Boehringer-Ingelheim, Merck, Pfizer, Roche, Schering Plough, and Tibotec for research unrelated to this study, and has received honoraria from Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, and Tibotec. All other authors: no conflicts.
Funding Information:
1Johns Hopkins University, Baltimore, and 2Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 3 Statistical and Data Analysis Center, Harvard University School of Public Health, Boston, Massachusetts; 4University of Pennsylvania School of Medicine, Philadelphia; 5New York University School of Medicine and 6Beth Israel Medical Center, New York, and 7Frontier Science and Technology Research Foundation, Amherst, New York; 8University of North Carolina, Chapel Hill; and 9University of Witswaterand, Johannesburg, South Africa
Funding Information:
Financial support. National Institutes of Health and National Institute of Allergy and Infectious Diseases (grants U01 AI68636 and AI068634). Abbott Laboratories, Bristol-Myers Squibb, and Gilead Pharmaceuticals provided study medications.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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 virologie 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.
AB - 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 virologie 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.
UR - https://www.scopus.com/pages/publications/77749329017
U2 - 10.1086/651118
DO - 10.1086/651118
M3 - Article
C2 - 20192725
AN - SCOPUS:77749329017
SN - 1058-4838
VL - 50
SP - 1041
EP - 1052
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 7
ER -