HIV Prevention Trials Network (HPTN) 052 was a multi-national, clinical trial that demonstrated reduced HIV transmission and health benefits of early antiretroviral treatment (ART). The study enrolled 1,763 serodiscordant couples and followed them for up to 10 years (2005-2015). At enrollment, HIV-infected index participants were randomized to the early ART arm (CD4: 350-550 cells/mm3 at ART initiation) or the delayed ART arm (CD4: ≤250 cells/mm3 at ART initiation). All index participants were offered ART at any CD4 cell count after the release of interim study results in May 2011. The rate of virologic failure was similar in the two study arms. We evaluated factors associated with HIV drug resistance in HPTN 052 participants with virologic failure.
Virologic failure was defined as two consecutive viral load measures >1,000 copies/mL after 24 weeks on ART. HIV drug resistance was evaluated at ART initiation (baseline) and virologic failure using the ViroSeq HIV-1 Genotyping System and the Resistance Calculator Program at Frontier Science Foundation (Stanford v7.0 algorithm). Factors associated with HIV drug resistance were analyzed using Chi-square, t-tests, and logistical regression models using SAS software.
HIV genotyping results were obtained at the time of ART initiation (baseline) and at virologic failure for 211 (84.7%) of 249 participants (128 early arm; 83 delayed arm [22 started ART before May 2011]). Overall, 4.7% of participants had resistance at baseline and 35.5% had new resistance at failure. The frequency of new resistance at failure was lower among participants in the early arm compared to all participants in the delayed arm (30.5% vs. 43.4%, p=0.06), and compared to the subset of participants in the delayed arm who started ART before May 2011 (54.5%, p=0.032). The frequency of new resistance at failure was lower among participants with higher baseline CD4 cell counts (p=0.047) and lower baseline viral loads (p=0.0001), and was higher among those receiving a regimen of efavirenz, lamivudine, and zidovudine compared to other ART regimens (p=0.0074). In a multivariate model, new resistance at failure was associated with baseline viral load (p=0.0008) and drug regimen (p=0.024).
The frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline (pre-ART) viral load.