Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia

Emergence of HIV-1 drug resistance limits effectiveness of antiretroviral therapy (ART). Since 2004 Georgia provides free ART to all patients in need. We aimed to evaluate drug resistance patterns of Georgian HIV-1 variants among patients with virologic failure. Study included adult HIV-1 patients, who experienced virologic failure and were found to carry drug resistant strains based on genotypic resistance testing in 2005-2013. HIV-1 pol gene sequences were examined for the presence of resistance-associated mutations. Stanford HIV Sequence Database was used for interpretation of resistance data. A total 193 patients were included in the study. Among them majority (86.5%) carried subtype A virus and nearly 80% were on Efavirenz-based regimen. The most common nucleoside reverse transcriptase inhibitor (NRTI) mutation was M184V - 86.0% (n=166). The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation was G190S, found in 105 (54.4%) of samples. Other significant NNRTI mutations included K101E (31.6%, n=61), K103N (30.1%, n=58) and Y181CI (26.9%, n=52). The prevalence of G190S was 62.3% in subtype A viruses compared to 3.8% in non-A variants (p<0.0001). Frequency of K101E was also significantly higher in subtype A (36.5% vs. 0%, p<0.0001). ). In 69 samples G190S co-occurred with either K101E or Y181C or with both: 39 genotypes G190S/K101E; 10 genotypes G190S/Y181CI and 20 genotypes G190S/K101E/Y181CI. High prevalence of G190S and K101 mutations suggests subtype A specific response to currently approved first-line NNRTIs. Frequent co-occurrence of G190S with Y181C and K101E may limit the use of novel generation NNRTIs in subtype A infected patients with previous exposure to this drug class.