This research will be done primarily in Peru as an extension of NIH grant #5 R0l HD36184. Widespread use of nevirapine chemoprophylaxis has been implemented to achieve moderately effective reduction of peripartum HIV- 1 transmission at a relatively low cost. Nevirapine, however, rapidly selects for drug resistant HIV- 1 as only a single base mutation, either K103N or Y181C, confer high-level resistance. Not surprisingly, HIV-l resistant to nevirapine has been detected in the plasma of women six weeks following a single dose of nevirapine. As a result of political and humanitarian efforts, the costs of certain antiretroviral medications have been markedly reduced. As systems are developed to provide therapy to economically disadvantaged populations, antiretroviral therapy will become more available for treatment of an increasing number of infected individuals. The increased availability of therapy for women in the near future warrants the use of chemoprophylactic regimens in pregnancy and during labor that will not compromise the effectiveness of future antiretroviral therapy by the selection of resistant virus. The proposed project will quantify the proportion of nevirapine resistant virus in the quasispecies of women of who receive single dose nevirapine for peripartum chemoprophylaxis of their infant, and defme its persistence and kinetics for six months postpartum. We also propose to detennine if co-administration of zidovudine and lamivudine (Combivir) for one week postpartum following the administration of nevirapine can prevent the selection of virus resistant to all three antiretrovirals. Lastly, we propose to transfer laboratory assays relevant to the investigation of mother-to-infant HIV-1 transmission and trials of antiretroviral therapy to investigators in Lima, Peru. A sensitive, simple and economical assay for early diagnosis of HIV- 1 in infants and a sensitive and economical oligo-ligase assay (OLA) that we have adapted to test for HIV-l resistance mutations will be transferred, including equipment and teaching of personnel. This proposal is an effort of further our commitment to the development of a research program in Peru that addresses issues pertinent to perinatal HIV-1l transmission, and to train and assist Peruvians investigators in this research.
