Single-dose nevirapine to prevent mother-to-child transmission of HIV type 1: balancing the benefits and risks.

Ever since the magnitude of the global AIDS epidemic was recognized, much effort has been directed toward understanding and decreasing mother-to-child transmission (MTCT) of HIV-1. The biologic complexity of the problem is compounded by the intertwined issues of poverty and limited access to care, leading scientists and policy makers to search for solutions that are both effective and practical in resource constrained settings. These forces were the impetus for tests of short courses of antiretroviral therapy for prevention of MTCT of HIV-1, such as third-trimester and neonatal administration of zidovu-dine [1] or a single intrapartum dose of nevirapine [2]. HIVNET 012 found that nevirapine (NVP) given as a single dose (sdNVP) decreased the risk of transmission of HIV-1 from mother to infant by 47%, compared with a short intrapartum and neonatal course of zidovudine [2]. This success, coupled with its economic feasibility and simplicity, led to adoption of sdNVP treatment for prevention of MTCT in many developing countries [3]. Potential maternal consequences of this approach became evident, however, with the important observation that NVP-resistant HIV-1 variants were selected in a substantial fraction of women who had received sdNVP [4, 5]. Whether these NVP-resistant variants would affect subsequent virologic response to antiretrovi-ral therapies containing NVP or other nonnucleoside reverse-transcriptase in-hibitors (NNRTIs) was not initially known. A subsequent study by Jourdain et al. [6] demonstrated that sdNVP treatment increased the risk of virologic failure in women who commenced NVP-containing antiretroviral therapy a median of 6.1 months after receipt of sdNVP, especially if NVP-resistant mutants were detected by a standard genotype assessment method when antiretroviral therapy was started. A subsequent study by Lockman et al. [7] provided some reassurance that the negative consequences of sdNVP therapy were temporary. Specifically, women who received NVP-containing antiretro-viral therapy after sdNVP had no higher risk of virologic failure if NVP-containing antiretroviral therapy was initiated 16 months after delivery, suggesting that NVP-resistant mutants decrease in frequency to less than clinically relevant levels within 6 months. However, a study using more-sensitive assays to quantify low-frequency NVP-resistant mutants showed that such mutants can persist in ∼20% of women for at least 1 year after receipt of sdNVP [8]. In this issue of Clinical Infectious Diseases , Coovadia et al. [9] present new data that help elucidate the influence of minor populations of NVP-resistant mutants (i.e., those that are not detected by standard genotype methods) on virologic response to NNRTI-containing antiretrovi-ral …