Minority HIV-1 drug-resistant mutations and prevention of mother-to-child transmission: perspectives for resource-limited countries.

Abstract

The detection and clinical significance of HIV-1 minority drug-resistant variants is a major topic of current HIV research. Whereas much attention has been placed on the clinical impact of minority drug-resistant variants in patients initiating antiretroviral therapy, their possible influence on the effectiveness of antiretroviral therapy following prevention of mother-to-child transmission strategies in resource-limited settings remains largely unexplored. This review outlines the clinical significance and detection of minority drug-resistant variants, focusing primarily on studies of minority variants in the context of prevention of mother-to-child transmission and their possible influence on current regimens, especially those available in resource-limited countries. The clinical impact of minority nevirapine-resistant variants that arise in the context of prevention of mother-to-child transmission, for example, is an important factor to consider when these women initiate antiretroviral therapy that may include nevirapine or efavirenz. Minority nonnucleoside reverse transcriptase inhibitor-resistant variants have been associated with treatment failure in women exposed to single-dose nevirapine. In countries like South Africa, with its longstanding use of single-dose nevirapine, this question is relevant as it is for other resource-limited countries where single-dose nevirapine is used. In the same context, various other minority drug-resistant variants (e.g. Y181C, K65R and thymidine analogue mutations etc.) are discussed. The field of next generation sequencing is very dynamic, with rapid improvements on present technologies and the introduction of novel technologies as discussed in this review. As the impact of minority drug-resistant variants in the setting of prevention of mother-to-child transmission becomes more evident, guidelines for this, especially in resource-limited countries, will need revision in order to optimize the clinical benefit from future antiretroviral therapy.