Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment.
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 >or= 100 000 copies/ml or CD4 cell counts below 50 cells/microl. Median CD4 recovery (ABC/3TC vs. TDF/FTC, cells/microl) 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.


CONCLUSIONS
Both ABC/3TC and TDF/FTC provided comparable antiviral efficacy, safety, and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients.
Smith
Kimberly Y
KY
Rush University Medical Center, Chicago, Illinois 60612, USA. Kimberly_Y_Smith@rush.edu
Patel
Parul
P
Fine
Derek
D
Bellos
Nicholaos
N
Sloan
Louis
L
Lackey
Philip
P
Kumar
Princy N
PN
Sutherland-Phillips
Denise H
DH
Vavro
Cindy
C
Yau
Linda
L
Wannamaker
Paul
P
Shaefer
Mark S
MS
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D002318:Cardiovascular Diseases / Q000139:chemically induced; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D000068679:Emtricitabine; D019259:Lamivudine; D061466:Lopinavir; D063065:Organophosphonates; D011744:Pyrimidinones; D012367:RNA, Viral; D019438:Ritonavir; D000068698:Tenofovir; D000099227:Abacavir