Genotypic antiretroviral drug resistance in a cohort of HIV infected drug naïve Ugandan Women

Abstract

Recently there has been increased access to ARVs in Uganda. There is high HIV diversity in Sub-Saharan Africa and very few data are available as to how subtype diversity may affect drug susceptibility and resistance. This study examined the genotypic HIV drug resistance in ART drug naïve patients in a Ugandan cohort as well as determining whether HIV-1 subtypes can be associated to drug resistance. In a crossection study of 104 ART naïve patients within one year of HIV serocoversion, 70 of the patients were genotyped for resistance to Reverse transcriptase inhibitors while 34 were genotyped for resistance to protease inhibitors. DNA was extracted from the PBMCs and both genes, the reverse transcriptase and Protease genes, were amplified by the PCR technique, after which they were then sequenced and analyzed for drug resistance using BioEdit sequence alignment editor (V 7.0.5.3) as well as the Stanford drug resistance data base. Subtyping was done using the Clustal X (V 1.83). HIV-1 subtypes A and D were the two major ones found in the cohort. Prevalence of resistance to NRTIs was higher in subtype A patients (13.3%) than other subtypes (C and D),while resistance to NNRTIs was higher in subtype D patients (9.0%), than in C or D subtypes, though none of this was significant. Further more, resistance to reverse transcriptase inhibitors could not be associated to any of the subtypes. All resistance mutations to protease inhibitors were minor drug mutations. Resistance to protease inhibitors was significantly higher in subtype A than D. Proportions of individuals that carried atleast 2 drug resistance mutations for each of the subtypes A and D were 100% and 50% respectively. There was a fairly high prevalence of resistance to reverse transcriptase inhibitors (12.9%). Though resistance to PIs was minor, this could lead to higher level resistance in presence of major mutations. Subtype A patients can therefore be predicted to fail PI therapy earlier than patients harboring subtype D virus because of the numerous minor resistance polymorphisms that can increase the fitness of the drug resistant virus.