AIDS care and treatment initiatives are anticipated to provide antiretroviral (ARV) treatment for 3 million people living with HIV/AIDS (PLWHA) in resource limited countries by 2005, the majority is infected by subtype C HIV-1, a widely dispersed virus responsible for HIV-1 infection in high prevalence populations in Southern Africa, Ethiopia, India and China. Reverse transcriptase inhibitor (RTI) ARV drugs, currently recommended as first-line therapy for HIV infection, are widely used in prevention of mother-to-child transmission (MTCT) as short-course regimens or single dose Nevirapine (SD NVP). Although SD NVP reduces MTCT by approximately 50%, rapid, complex selection of drug resistant virus has been documented in the majority of subtype C infected women and infected infants exposed to SD NVP. While drug resistant virus disappears (as detected by sequencing) from plasma RNA, archival resistant proviral DNA persists is thought to persist, potentially for years following exposure to NVP and other antiretroviral drugs (ARV). ARV therapy is expected to dramatically increase in developing countries, and viral drug resistance evolution will inevitably take place. Viruses from patients exposed to ARV drugs demonstrate phenotypic changes in drug susceptibility and envelope chemokine receptor tropism. Resistance to ARV drugs and the syncytia inducing (SI) phenotype are associated with distinct genotypic mutations in gag-pol and the V-3 loop of the env gene, respectively. These phenotypes are associated with rapid disease progression and mortality in HIV-1.
The aim i s to study the pathogenesis of subtype C HIV-1 in women and infants after ARV including SD NVP to optimize clinical benefits of ARV treatment and prevention of MTCT.
