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

Abstract

Purpose of the studyFew 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.MethodsObservational retrospective study of 664 consecutive treatment‐naïve 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 (<1 log RNA HIV‐1 decrease in first 3 months); b) RNA HIV‐1 >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.Results62% 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 log10 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).ConclusionsInitial 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.