The epidemic of HIV-1 in southern Africa is characterized by the predominance of infections caused by subtype C. This is the major subtype in Botswana where HIV prevalence in adults is estimated to be 37%. The goals of the World Health Organization to provide antiretrovirals (ARVs) to three million people by 2005 will provide an opportunity for great numbers of people to become healthy and live productive lives with HIV. This introduction of ARVs, however, needs to be accompanied by further research into viral resistance in the non-subtype B clades as limited knowledge exists about resistance in these subtypes. The central hypothesis to be examined is that more sensitive assays can detect viral resistance in women who have received nevirapine for the prevention of mother-to-child transmission (PMTCT) and that this information can predict clinical outcomes once the women commence ARVs. To address this hypothesis, we are optimizing both an oligonucleotide ligation assay and allele specific real time-polymerase chain reaction technique on samples which are known to contain resistant mutations. These assays, specific to HIV-1 C, will be used on clinical samples to detect mutations at the two most common sites which confer nevirapine resistance. The clinical relevance of minor variant resistance will be explored as these techniques will be applied to samples from women in whom conventional genotyping techniques have not detected resistance mutations after receiving PMTCT. If minor variants causing clinical virologic failure are detected by these more sensitive methods, these variants may have an important role in explaining virologic failure in patients receiving nonnucleoside reverse transcriptase inhibitor therapy. The analyses conducted will also address issues such as the persistence of mutations over time and variations in resistance patterns across different viral reservoirs after single-dose nevirapine. The public health implications of this research are significant in that it will provide a more complete understanding of resistance after single-dose nevirapine and correlate it with clinical outcomes for the women who receive this therapy and then start on ARVs. Research into nevirapine resistance after single-dose and its impact on future maternal health can help to increase the fund of knowledge about issues of resistance in non-subtype B HIV, help with public policy decisions about PMTCT, and serve to improve the care of patients during the rapid expansion of ARV use in resource-poor settings.
| Rowley, Christopher F; Boutwell, Christian L; Lee, Esther J et al. (2010) Ultrasensitive detection of minor drug-resistant variants for HIV after nevirapine exposure using allele-specific PCR: clinical significance. AIDS Res Hum Retroviruses 26:293-300 |
| Rowley, Christopher F; Boutwell, Christian L; Lockman, Shahin et al. (2008) Improvement in allele-specific PCR assay with the use of polymorphism-specific primers for the analysis of minor variant drug resistance in HIV-1 subtype C. J Virol Methods 149:69-75 |
