Analysis of polymorphism in the protease and reverse transcriptase genes of HIV type 1 CRF02-AG subtypes from drug-naive patients from Saint-Etienne, France.

Summary: : The proportion of non-B HIV-1 variants is increasing in Western Europe. The impact of the high polymorphism in the protease and reverse transcriptase genes, as recently described for CRF02-AG isolates of African origin, on antiretroviral resistance is still disputed. We first examined the polymorphism of these genes in CRF02-AG strains recovered from drug-naive patients followed at the University Hospital of Saint-Etienne in France, most of these of French origin and harboring a clonal strain as elicited by phylogenic analysis. The first plasma sample detected positive from 31 CRF02-AG and 23 B strains was used to compare sequences with their respective subtype consensus strain. The overall number of mutations was dramatically higher for CRF02-AG strains than for B strains in both protease and reverse transcriptase genes (P < 0.0001 and 0.009, respectively). In addition, no statistically significant difference in the number of therapeutic failures, mean CD4 cell count, and viral load was observed between 22 and 45 patients infected with CRF02-AG or B strains, respectively, during a mean treatment period of 25.5 months. Even if no striking antiretroviral failure linked to this polymorphism was observed during short-term follow-up, its impact on long-term therapy will have to be extensively evaluated in patients infected by non-B HIV-1 variants.