Predictors of Virologic Failure and Resistance in HIV-Infected Patients Treated with Nevirapine- or Efavirenz-Based Antiretroviral Therapy

TLDR

Resistance to NNRTIs rises with broader use, and the link between adherence and resistance remains poorly understood. The study sought to identify predictors of virologic failure and resistance using baseline nonadherence risk factors in 71 HIV‑infected patients with early virologic response on NNRTI‑based therapy. Baseline nonadherence risk factors were assessed in this cohort to determine these predictors. Over a median 29‑month follow‑up, 28 % of patients experienced virologic failure, which was associated with repeated drug holidays, depression, younger age, and low baseline adherence; repeated drug holidays were the only factor linked to major NNRTI cross‑resistance mutations, and prior adherence and drug genetic barriers should guide therapy simplification.

Abstract

Resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) increases with the wider use of this class of antiretroviral therapy. The association between adherence and resistance to NNRTI-based regimens is poorly understood. Predictors of virologic failure and resistance according to a baseline evaluation of nonadherence risk factors were determined in a cohort of 71 human immunodeficiency virus (HIV)-infected patients with early virologic response who received an NNRTI-based regimen. During the median follow-up of 29 months, 20 (28%) of 71 patients experienced virologic failure with an NNRTI-based regimen. Virologic failure was associated with repeated drug holidays (> or =48 h of unplanned drug cessation), depression, younger age, and low adherence to therapy during baseline evaluation. Moreover, repeated drug holidays was the only risk factor for developing a major mutation conferring cross-resistance to the NNRTI class (hazard ratio, 22.5; 95% confidence interval, 2.8-180.3; P<.0001). Patients' previous adherence to therapy and drugs genetic barriers, not only the number of pills or doses involved, should be taken into consideration in the decision to simplify highly active antiretroviral therapy.