Prevalence of antiretroviral drug resistance mutations among pre-treatment and ART-failured HIV patients in Uzbekistan.

OBJECTIVE To evaluate the national prevalence of antiretroviral therapy (ART)-resistant HIV-1 viruses among both ART-initiators (pre-treatment resistance, PDR) and ART-failured HIV patients in Uzbekistan. METHODS A nation-wide, cross-sectional active HIV-1 PDR surveillance was conducted in Uzbekistan from 2015-2016. In total, 713 blood plasma samples from adults were collected including samples from ART-naive patients initiating ART and ART-failured HIV patients. HIV-1 genome polregion viral sequences were obtained from 309 patients, of those 106 on ART and 203 - ART-initiators. Analysis of HIV-1 subtypes and drug resistance mutations to HIV protease and reverse transcriptase inhibitors was performed. RESULTS Among all the viruses studied, HIV-1 CRF 02_AG recombinant was the most common - 57% (176/309). The second major group was represented by A1 - 40.5% (125/309). Two viruses were found to be recombinants formed by subtypes A1 and CRF02_AG sequences. ART-naive cohort I (PDR) included 6 samples that contained at least one surveillance drug resistance mutation (SDRM) (2.96%), with the most common being K103N mutation (4/6). In ART-experienced patients cohort II 77.4% (82/106) of viruses contained at least one mutation against PIs, NRTIs or NNRTIs, with the most common mutations of M184V/I (49.1%; 52/106), K65R (18.9%; 20/106), K103N (23.6%, (25/106), and G190S (22.6%; 24/106). The significant difference in frequency of mutations was found between two dominant subtypes, A1 and CRF02_AG. CONCLUSION The molecular-epidemiological profile of HIV infection in Uzbekistan has changed towards a predominance of CRF02_AG viruses. The first national scale study of the PDR prevalence it was found to be relatively low (2.96%). The DR mutations in failured patients correspond to the main treatment regimens (NRTI/NNRTI) adopted in the country. The observations provide new evidence for differences in ART efficacy and resistance profiles for different subtypes.