Nevirapine resistance after single dose prophylaxis

Abstract

Nevirapine (NVP) is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase. In 1999, the HIVNET 012 trial in Uganda demonstrated that a simple regimen of NVP prophylaxis can dramatically reduce the rate of HIV-1 mother-to-child transmission (MTCT). In the HIVNET 012 regimen, women received a single dose of NVP in labor, and infants received a single dose of NVP within 72 h of birth. The simplicity, efficacy, and low cost of the HIVNET 012 regimen are attractive for prevention of MTCT in resource-poor settings. Plans are underway to implement this regimen in several resource-poor countries. Single mutations in HIV-1 RT can cause high level NVP-resistance and are likely to exist in most HIV-1 infected patients at low levels prior to antiretroviral drug exposure. This favors emergence of NVP-resistant HIV-1 following NVP exposure. NVP-resistant HIV-1 has been shown to emerge in some women and infants following single dose NVP. Emergence of NVP-resistant HIV-1 in this setting is more common among women with high baseline viral loads and low baseline CD4 cell counts. The rate of NVP-resistance in women receiving single dose NVP prophylaxis may also be influenced by HIV-1 subtype. The NVP-resistant HIV-1 typically fades from detection in women and infants over time. We review studies examining the emergence and fading of NVP-resistant HIV-1 in women and infants who received single dose NVP prophylaxis, and discuss the potential clinical relevance of NVP-resistance in this setting.