Intensification of a Triple-nucleoside Regimen with Efavirenz or Tenofovir

By Brian Boyle, MD

Few studies of quadruple-nucleoside (NRTI) ARV regimens have been performed, and the results from these studies have been variable, with performances that were relatively good (TIMS with twice daily Trizivir (co-formulated abacavir [ABC]/zidovudine [ZDV]/lamivudine [3TC])+ TDF QD) and relatively poor (COLA 40263 with once daily Trizivir (co-formulated abacavir [ABC]/zidovudine [ZDV]/lamivudine [3TC] )+ TDF QD.

In the ACTG 5095 trial, ARV-naïve subjects randomized originally to receive co-formulated abacavir [ABC]/zidovudine [ZDV]/lamivudine [3TC] twice daily and who suppressed HIV RNA to <200 copies/ml (c/ml) were re-randomized to intensify with either efavirenz [Sustiva] (EFV arm) or tenofovir [Viread] (TDF arm).

Of the 382 subjects randomized originally to co-formulated abacavir [ABC]/zidovudine [ZDV]/lamivudine [3TC], 208 had HIV RNA <200 c/ml after a median 36 weeks treatment.  Of them, 170 (21% women; 56% non-white) chose to intensify using either EFV or TDF.  At baseline, 73% had an HIV RNA <50 c/ml and the median CD4 count was 453 cells/mm3.

Over a median follow-up of 79 wks, 163 (96%) completed the study, 5 (3%) discontinued early and 2 (1%) died.  Overall, treatment failure occurred in 32 subjects: 13 (15%) in the EFV arm and 19 (22%) in the TDF arm (p=0.28).  Interestingly, while the 2 arms were similar overall, there was a significant change in treatment effect over time (p=0.03), with more early treatment failures (and none after week 40) in the EFV arm and more later treatment failures on the TDF arm. 

Overall, HIV RNA was suppressed through 48 wks in >89% of subjects to <200 c/ml and in >79% to <50 c/ml, without significant differences by treatment arm.  There were no significant differences between arms in CD4 increases, time to new grade 3 or 4 adverse events, or adherence rates.

The authors conclude, “In subjects with virologic suppression on triple nucleosides, intensifying with efavirenz was not different to intensifying with tenofovir in safety and efficacy over a median 1.5 years of follow-up.  The relative effect of treatment between the two regimens changed over time.”

02/07/06

Reference
R Gulick et al. Randomized Intensification of a Triple-Nucleoside Regimen with Efavirenz or Tenofovir in ACTG 5095. 13^th Conference on Retroviruses and Opportunistic Infections. Denver, CO. February 5-8, 2006. Abstract 519.