Effectiveness of first-line antiretroviral therapy based on NNRTIs vs ritonavir-boosted PIs in HIV-1 infected patients with high plasma viral load

Purpose of the study : Few clinical trials have compared non-nucleoside reverse transcriptase inhibitors (NNRTI) and ritonavir-boosted protease inhibitors (PI/r) as initial combined antiretroviral therapy (cART) for HIV-1-infected patients with high plasma viral load (pVL), and non-conclusive results have been reported. We compared the effectiveness between NNRTI and PI/r as first-line cART for HIV-1-infected patients with high pVL. Methods: Observational retrospective study of 664 consecutive treatment-naive HIV-1-infected patients with pVL (HIV-1 RNA) >100,000 copies/mL who initiated NNRTI or PI/r-based cART between 2000-2010 in three University hospitals. Only currently preferred or alternative regimens in clinical guidelines were included. Primary endpoint: percentage of therapeutic failures at week 48. Virologic failure was defined as: a) lack of virologic response ( 50 c/mL at week 48; c) confirmed rebound >50 c/ml after a previous value <50 c/mL. Intent-to-treat (ITT noncompleter=failure) and on-treatment (OT) analyses were performed. Results: 62% of patients initiated NNRTI-regimens (83% efavirenz) and 38% PI/r-regimens (62% lopinavir/). Baseline characteristics: male 83%; median age 39 yrs; median CD4 count: 212/μL (NNRTI 232 vs PI/r 177, p=0.028); pVL 5.83 log 10 c/mL (NNRTI 5.43 vs PI/r 5.55, p=0.007); AIDS 24% (NNRTI 21% vs PI/r 29%, p=0.015). NRTI backbones were tenofovir plus 3TC or FTC in 72%. The percentage of therapeutic failure was higher in the PI/r group (ITT NC=F 26% vs 18%, p=0.012) with no differences in virologic failures (PI/r 5%, NNRTI 6%, p=0.688). The rate of treatment changes due to toxicity and/or voluntary discontinuations was higher in the PI/r group (15% vs 8%, p=0.008). A multivariate analysis adjusted for age, gender, CD4 count, VL and AIDS showed NNRTI vs PI/r as the only variable associated with treatment response (OR 0.61, 95% CI 0.41-0.88). Median pVL and rate of resistance at virologic failure were higher in patients receiving NNRTI (3.97 vs 2.49 log copies/mL, p<0.001 and 62% vs 12%, p=0.004, respectively). Conclusions: Initial NNRTI-regimens showed higher effectiveness compared with PI/r-regimens in HIV-1-infected patients with high pVL, although virologic failure rates were low and comparable. Resistance emergence was more frequent and pVL higher in patients failing NNRTI. However, more patients initiating PI/r-based regimens changed or discontinued therapy. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Imaz A et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18235 http://www.jiasociety.org/index.php/jias/article/view/18235 | http://dx.doi.org/10.7448/IAS.15.6.18235