Background:  Prior nevirapine (NVP) for prevention of mother-to-child transmission (PMTCT) has been associated with selection of NNRTI-resistant mutations, which may significantly reduce the efficacy of an NNRTI-based combination ART (cART ), resulting in early virologic failure and poor CD4 gain. We investigated the effect of prior NVP use on viral responses and CD4 gain for patients after cART initiation.

Methods:  We undertook a retrospective analysis of prior NVP use in Phidisa II, a completed, randomized, controlled trial comparing the safety and efficacy of 4 first-line cART regimens among a South African military healthcare cohort. Patients with <7 days of prior ART were randomized to 1 of 4 regimens containing either efavirenz (EFV) or lopinavir/ritonavir (LPV/r). Information from patients who reported prior use of NVP was recorded at study entry. The level of virologic failure (defined as HIV-1 RNA >400 copies/mL) and CD4 count changes at 6 months after cART, were compared between NVP and no NVP exposure (no-NVP) women. Fisher’s exact test was used to compare rates of virologic failure between the 2 groups, while the t test was used to compare CD4 change.

Results:  At study entry, 1401 participants responded to the question on prior ART use. Of these, 478 were women, of whom 392 had no NVP exposure and 86 had NVP exposure. No participants reported the use of other ARV in addition to NVP. Of the 478 women, 394 had HIV RNA observed 6 months after cART initiation (324 no-NVP, 70 NVP). Of the no-NVP group, 30.1% experienced virologic failure, compared to 31.4% in the NVP group (OR 1.1, p = 0.886). When stratified for treatment arm, there was still no statistically significant difference in failure rates among NVP vs no-NVP subjects (OR 0.98, p = 1 over EFV arms, compared to OR 1.17, p = 0.70 over LPV/r arms). The baseline to 6-month gain in CD4 counts was 15 cells greater for NVP-exposed women in the EFV arms (p = 0.33) and 8 cells lower in the LPV/r arms (p = 0.65).

Conclusions:  In this cohort, prior NVP use had no effect on virologic failure at 6 months, either over all arms or within treatment arms (EFV vs LPV/r). There was also no effect of NVP on CD4 gain. This lack of effect of prior NVP use may be due to the time lapse (although unknown) between the NVP exposure and randomization. This suggests that NNRTI-based regimens may be used with good results in patients with prior single-dose NVP exposure.