Transmitted HIV Drug Resistance in Bulgaria Occurs in Clusters of Individuals from Different Transmission Groups and Various Subtypes (2012-2020)

Viruses. 2023 Apr 10;15(4):941. doi: 10.3390/v15040941.

Abstract

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.

Keywords: HIV-1; male-to-male sexual contact; subtypes; transmission clusters; transmitted drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Bulgaria / epidemiology
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • HIV Seropositivity*
  • HIV-1* / genetics
  • Humans
  • Male
  • Mutation
  • Phylogeny
  • Prevalence
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Reverse Transcriptase Inhibitors
  • methionylmethylsulfonium chloride
  • Anti-HIV Agents

Grants and funding

The study was supported by the Ministry of Health, National Program for Prevention and Control of HIV and Sexually Transmitted Infections in Bulgaria, by the European Regional Development Fund through Operational Program Science and Education for Smart Growth 2014–2020, Grant BG05M2OP001-1.002-0001-C04 “Fundamental Translational and Clinical Investigations on Infections and Immunity”.