Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment

Smith, Kimberly Ya; Patel, Parulb; Fine, Derekc; Bellos, Nicholaosd; Sloan, Louise; Lackey, Philipf; Kumar, Princy Ng; Sutherland-Phillips, Denise Hb; Vavro, Cindyb; Yau, Lindab; Wannamaker, Paulb; Shaefer, Mark Sb; for the HEAT study team

AIDS:
doi: 10.1097/QAD.0b013e32832cbcc2
Clinical Science
Abstract

Background: Abacavir sulfate/lamivudine (ABC/3TC) and tenofovir DF/emtricitabine (TDF/FTC) are widely used nucleoside reverse transcriptase inhibitors for initial HIV-1 treatment. This is the first completed, randomized clinical trial to directly compare the efficacy, safety, and tolerability of these agents, each in combination with lopinavir/ritonavir in antiretroviral-naive patients.

Methods: Six hundred and eighty-eight antiretroviral-naive, HIV-1-infected patients were randomized in this double-blind, placebo-matched, multicenter, noninferiority study to receive a once-daily regimen of either ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg, both with lopinavir/ritonavir 800 mg/200 mg. Primary endpoints were the proportion of patients with HIV-1 RNA below 50 copies/ml at week 48 (missing = failure, switch included analysis) and the proportion of patients experiencing adverse events over 96 weeks.

Results: At week 48, 68% in the ABC/3TC group vs. 67% in the TDF/FTC group achieved an HIV-1 RNA below 50 copies/ml (intent-to-treat exposed missing = failure, 95% confidence interval on the difference −6.63 to 7.40, P = 0.913), demonstrating the noninferiority of ABC/3TC to TDF/FTC at week 48. Noninferiority of the two regimens was sustained at week 96 (60% vs. 58%, respectively, 95% confidence interval −5.41 to 9.32, P = 0.603). In addition, efficacy of both regimens was similar in patients with baseline HIV-1 RNA ≥ 100 000 copies/ml or CD4+ cell counts below 50 cells/μl. Median CD4+ recovery (ABC/3TC vs. TDF/FTC, cells/μl) was +250 vs. +247 by week 96. Premature study discontinuation due to adverse events occurred in 6% of patients in both groups. Protocol-defined virologic failure occurred in 14% of patients in both groups.

Conclusion: Both ABC/3TC and TDF/FTC provided comparable antiviral efficacy, safety, and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients.

Author Information

aRush University Medical Center, Chicago, Illinois, USA

bGlaxoSmithKline, Research Triangle Park, North Carolina, USA

cJohns Hopkins University School of Medicine, Baltimore, Maryland, USA

dSouthwest Infectious Disease Associates, USA

eNorth Texas Infectious Disease Consultants, Dallas, Texas, USA

fID Consultants, Charlotte, North Carolina, USA

gGeorgetown University, Washington, District of Columbia, USA.

* Other members are listed at end of paper.

Received 18 February, 2009

Revised 6 April, 2009

Accepted 9 April, 2009

Correspondence to Kimberly Y. Smith, MD, MPH, Rush University Medical Center, 600 South Paulina Street, Suite #143, Chicago, IL 60612, USA. Tel: +1 312 942 5865; fax: +1 312 942 8200; e-mail: Kimberly_Y_Smith@rush.edu

© 2009 Lippincott Williams & Wilkins, Inc.