Viral latency and reservoirs: relevance for mother-to-child transmission and resistance

Abstract

Purpose of review: This review summarizes recent data regarding the development of HIV resistance among women provided with single-dose nevirapine, alone or in combination with other antiretroviral agents to prevent mother-to-child transmission. Traditional sequencing methods and methods to detect low levels of mutations are reviewed and contrasted with methods to detect archived resistance within resting CD4 T cells.

Recent findings: Nevirapine resistance can be detected in 18-69% of plasma-based sequencing assays. Highly sensitive, mutation-specific polymerase chain reaction methods have found nevirapine-resistant virus in up to 89% of samples immediately after nevirapine administration and at lower levels for up to 12 months after exposure. Studies to assess the presence of nevirapine-resistant virus archived in cells have yielded inconclusive results. Rigorous analysis to uncover the archiving of non-nucleoside reverse transcriptase inhibitor resistance mutations in the latent cellular reservoir after single-dose nevirapine is lacking.

Summary: Prevention of the transmission of HIV from mother to child is an important public health problem for resource-limited countries. Simple and effective methods to reduce transmission such as single-dose nevirapine given to the mother during labor and to the infant are practical interventions, but a majority of women will subsequently develop HIV resistance mutations. There are limited, but compelling data to suggest that single-dose nevirapine can lead to persistent, and possibly archived, non-nucleoside reverse transcriptase inhibitor resistance, thus placing women at risk of virological failure when rechallenged with non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.