Background:  Clinical trials commonly use differences in surrogate markers, such as short-term virologic failure, to evaluate initial combination ART (cART) regimens. Whether these translate to differences in clinical outcomes is not well established. We compared short-term virologic failure and clinical outcomes in patients treated with commonly used cART regimens.

Methods:  Data from 15 HIV cohort studies in Europe and North America were combined. Eligible patients were aged >15, ART-naive when they started cART, and started cART after December 31, 1999. Data from patients treated with zidovudine/lamivudine (ZDV/3TC) in combination with efavirenz (EFV), nevirapine (NVP), lopinavir (LPV), nelfinavir (NFV), idinavir (IDV), or abacavir (ABC) are presented. Logistic regression and Cox models were used to estimate odds ratios (OR) of detectable 6 month HIV RNA (>500 copies/mL) and hazard ratios (HR) for the composite clinical outcome AIDS or death within 2 years of starting cART. Analyses were done by intention-to-treat, were stratified by cohort, and were adjusted for age, sex, injecting drug users, clinical stage, CD4, HIV RNA and year of starting cART.

Results:  Of 20,260 patients starting cART, 12,364 (61%) were treated with ZDV/3TC in combination with EFV, NVP, LPV, NFV, IDV, or ABC. In general, triple nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI), and protease inhibitor (PI) regimens were prescribed to those with high, intermediate, and low CD4 counts, respectively. The table below compares virologic and clinical outcomes among these regimens.

Conclusions:  Detectable viremia at 6 months was more common with all other third drugs compared with EFV (combined with ZDV/3TC). However, between-regimen differences in clinical outcomes were much less marked. Differences in short-term virologic failure between cART regimens may not translate to differences in clinical outcomes.