Identifying HIV-1 Transmission Clusters in Uzbekistan through Analysis of Molecular Surveillance Data.

The CRF02_AG and sub-subtype A6 are currently the predominant HIV-1 variants in the Republic of Uzbekistan, but little is known about their time-spatial clustering patterns in high-risk populations. We have applied molecular evolution methods and network analyses to better understand the transmission patterns of these subtypes by analyzing 316 pol sequences obtained during the surveillance study of HIV drug resistance. Network analysis showed that about one third of the HIV infected persons were organized into clusters, including large clusters with more than 35 members. These clusters were composed mostly of injecting drug users and/or heterosexuals, with women having mainly high centrality within networks identified in both subtypes. Phylogenetic analyses of the 'Uzbek' sequences, including those publicly available, show that Russia and Ukraine played a role as the main sources of the current subtype A6 epidemic in the Republic. At the same time, Uzbekistan has been a local center of the CRF02_AG epidemic spread in the former USSR since the early 2000s. Both of these HIV-1 variants continue to spread in Uzbekistan, highlighting the importance of identifying transmission networks and transmission clusters to prevent further HIV spread, and the need for HIV prevention and education campaigns in high-risk groups.

Prevalence of Antiretroviral Drug Resistance Mutations Among Pretreatment and Antiretroviral Therapy-Failure HIV Patients in Uzbekistan.

To evaluate the national prevalence of antiretroviral therapy (ART)-resistant HIV-1 viruses among both ART-initiators (pretreatment drug resistance, PDR) and ART-failure HIV patients in Uzbekistan. A nation-wide, cross-sectional active HIV-1 PDR surveillance was conducted in Uzbekistan from 2015 to 2016. In total, 713 blood plasma samples from adults were collected, including samples from ART-naive patients initiating ART and ART-failure HIV patients. HIV-1 genome polregion viral sequences were obtained from 309 patients, of those 106 on ART and 203 on ART-initiators. Analysis of HIV-1 subtypes and drug resistance mutations (DRMs) to HIV protease and reverse transcriptase inhibitors was performed. 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 six 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. The molecular epidemiological profile of HIV infection in Uzbekistan has changed toward a predominance of CRF02_AG viruses. In the first national-scale study of the PDR prevalence, it was found to be relatively low (2.96%). The DR mutations in failure patients correspond to the main therapy regimens (NRTI/NNRTI) adopted in the country. The observations provide new evidence for differences in ART efficacy and resistance profiles for different subtypes.