PMID- 37112921 OWN - NLM STAT- MEDLINE DCOM- 20230501 LR - 20230501 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 15 IP - 4 DP - 2023 Apr 10 TI - Transmitted HIV Drug Resistance in Bulgaria Occurs in Clusters of Individuals from Different Transmission Groups and Various Subtypes (2012-2020). LID - 10.3390/v15040941 [doi] LID - 941 AB - Transmitted HIV drug resistance in Bulgaria was first reported in 2015 using data from 1988-2011. We determined the prevalence of surveillance drug resistance mutations (SDRMs) and HIV-1 genetic diversity in Bulgaria during 2012-2020 using polymerase sequences from 1053 of 2010 (52.4%) antiretroviral therapy (ART)-naive individuals. Sequences were analyzed for DRM using the WHO HIV SDRM list implemented in the calculated population resistance tool at Stanford University. Genetic diversity was inferred using automated subtyping tools and phylogenetics. Cluster detection and characterization was performed using MicrobeTrace. The overall rate of SDRMs was 5.7% (60/1053), with 2.2% having resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 1.8% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 2.1% to protease inhibitors (PIs), and 0.4% with dual-class SDRMs. We found high HIV-1 diversity, with the majority being subtype B (60.4%), followed by F1 (6.9%), CRF02_AG (5.2%), A1 (3.7%), CRF12_BF (0.8%), and other subtypes and recombinant forms (23%). Most (34/60, 56.7%) of the SDRMs were present in transmission clusters of different subtypes composed mostly of male-to-male sexual contact (MMSC), including a 14-member cluster of subtype B sequences from 12 MMSC and two males reporting heterosexual contact; 13 had the L90M PI mutation and one had the T215S NRTI SDRM. We found a low SDRM prevalence amid high HIV-1 diversity among ART-naive patients in Bulgaria during 2012-2020. The majority of SDRMs were found in transmission clusters containing MMSC, indicative of onward spread of SDRM in drug-naive individuals. Our study provides valuable information on the transmission dynamics of HIV drug resistance in the context of high genetic diversity in Bulgaria, for the development of enhanced prevention strategies to end the epidemic. FAU - Alexiev, Ivailo AU - Alexiev I AUID- ORCID: 0000-0002-3186-1124 AD - National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Shankar, Anupama AU - Shankar A AD - Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. FAU - Pan, Yi AU - Pan Y AD - Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. FAU - Grigorova, Lyubomira AU - Grigorova L AD - National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Partsuneva, Alexandra AU - Partsuneva A AD - National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Dimitrova, Reneta AU - Dimitrova R AUID- ORCID: 0000-0001-7711-6798 AD - National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Gancheva, Anna AU - Gancheva A AD - National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Kostadinova, Asya AU - Kostadinova A AD - National Reference Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Elenkov, Ivaylo AU - Elenkov I AD - Specialized Hospital for Active Treatment of Infectious & Parasitic Diseases, 1606 Sofia, Bulgaria. FAU - Yancheva, Nina AU - Yancheva N AUID- ORCID: 0000-0002-0095-263X AD - Specialized Hospital for Active Treatment of Infectious & Parasitic Diseases, 1606 Sofia, Bulgaria. FAU - Grozdeva, Rusina AU - Grozdeva R AD - Specialized Hospital for Active Treatment of Infectious & Parasitic Diseases, 1606 Sofia, Bulgaria. FAU - Strashimirov, Dimitar AU - Strashimirov D AD - Specialized Hospital for Active Treatment of Infectious & Parasitic Diseases, 1606 Sofia, Bulgaria. FAU - Stoycheva, Mariana AU - Stoycheva M AD - Department of Infectious Diseases, Medical University, 4002 Plovdiv, Bulgaria. FAU - Baltadzhiev, Ivan AU - Baltadzhiev I AD - Department of Infectious Diseases, Medical University, 4002 Plovdiv, Bulgaria. FAU - Doichinova, Tsetsa AU - Doichinova T AD - Department of Infectious Diseases, Medical University, 5800 Pleven, Bulgaria. FAU - Pekova, Lilia AU - Pekova L AD - Clinic of Infectious Diseases, Medical University, 6000 Stara Zagora, Bulgaria. FAU - Kosmidis, Minas AU - Kosmidis M AD - Clinic of Infectious Diseases, Medical University, 9002 Varna, Bulgaria. FAU - Emilova, Radoslava AU - Emilova R AUID- ORCID: 0000-0002-0018-1361 AD - National Reference Laboratory of Immunology, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Nikolova, Maria AU - Nikolova M AD - National Reference Laboratory of Immunology, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria. FAU - Switzer, William M AU - Switzer WM AUID- ORCID: 0000-0003-4591-8731 AD - Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230410 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Reverse Transcriptase Inhibitors) RN - 3493-12-7 (methionylmethylsulfonium chloride) RN - 0 (Anti-HIV Agents) SB - IM MH - Humans MH - Male MH - Reverse Transcriptase Inhibitors/therapeutic use MH - Bulgaria/epidemiology MH - Drug Resistance, Viral/genetics MH - Mutation MH - *HIV Infections/drug therapy/epidemiology MH - *HIV Seropositivity MH - *HIV-1/genetics MH - Prevalence MH - Phylogeny MH - Genotype MH - *Anti-HIV Agents/pharmacology/therapeutic use PMC - PMC10146724 OTO - NOTNLM OT - HIV-1 OT - male-to-male sexual contact OT - subtypes OT - transmission clusters OT - transmitted drug resistance COIS- The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. EDAT- 2023/04/28 06:41 MHDA- 2023/05/01 06:42 PMCR- 2023/04/10 CRDT- 2023/04/28 01:54 PHST- 2023/02/12 00:00 [received] PHST- 2023/04/04 00:00 [revised] PHST- 2023/04/08 00:00 [accepted] PHST- 2023/05/01 06:42 [medline] PHST- 2023/04/28 06:41 [pubmed] PHST- 2023/04/28 01:54 [entrez] PHST- 2023/04/10 00:00 [pmc-release] AID - v15040941 [pii] AID - viruses-15-00941 [pii] AID - 10.3390/v15040941 [doi] PST - epublish SO - Viruses. 2023 Apr 10;15(4):941. doi: 10.3390/v15040941.