Molecular Characterization of HIV-1 Subtypes and Primary Drug Resistance Mutations in Bangladesh: Insights from 2019 Data

Human Immunodeficiency Virus Type 1 (HIV-1) continues to pose a major public health challenge in Bangladesh, with increasing concern over genetic diversity and emerging drug resistance. This study aimed to investigate the molecular epidemiology, subtype distribution, co-receptor tropism, and Primary Drug Resistance Mutations (PDRMs) in treatment-naïve HIV-1-positive individuals in Bangladesh.

A cross-sectional study was conducted among 30 treatment-naïve HIV-1-positive individuals enrolled at the Department of Virology, BSMMU. Demographic and geographic data were recorded. RNA was extracted from plasma samples with viral loads ≥2000 copies/mL, and the Reverse Transcriptase (RT) and env gene regions were amplified via nested PCR and sequenced using the 3500Dx Genetic Analyzer. Subtypes were determined using REGA genotyping tools. Phylogenetic relationships were assessed using MEGA-X. Co-receptor usage was predicted via Geno2Pheno, and PDRMs were evaluated using the Stanford HIV Drug Resistance Database.

The study cohort had a male predominance (73%) with a mean age of 37 ± 12 years and originated from all eight administrative divisions of Bangladesh. Half of the participants had a history of international migration, particularly to Saudi Arabia. Subtyping identified all 30 sequences as HIV-1 subtype C using REGA. Phylogenetic analysis revealed strong clustering with regional strains from India, China, Malaysia, Iran, Myanmar, and South Africa, suggesting transnational transmission. Co-receptor analysis showed that 77% of sequences were CCR5-tropic and 23% were CXCR4-tropic. No major NRTI mutations were detected; however, NNRTI resistance mutations (V106I, G190V, V179D) were identified in 13% of cases. Additionally, a high frequency (77%) of the D121 polymorphism was observed.

This study provides valuable insights into the molecular epidemiology of HIV-1 in Bangladesh, reaffirming the predominance of subtype C, likely introduced through regional or international migration. The presence of major NNRTI-associated resistance mutations and CXCR4-tropic variants in a portion of treatment-naive individuals, although based on a limited sample size, raises concerns about emerging drug resistance and the potential impact on treatment outcomes. Although no major NRTI resistance mutations were identified, the presence of NNRTI-associated mutations in 13% of treatment-naïve cases is concerning, as transmitted drug resistance can compromise first-line therapy effectiveness. The high frequency of the D121 polymorphism, though not directly linked to treatment failure, reflects underlying genetic variability that may influence future resistance pathways.

This study confirms the predominance of HIV-1 subtype C in Bangladesh. The detection of NNRTI-associated resistance mutations and CXCR4-tropic variants in treatment-naïve cases raises concerns for future treatment effectiveness. This study highlights the need for ongoing molecular surveillance to track subtype diversity, detect early drug resistance, and support evidence-based strategies. Larger, updated studies are essential to validate these results and guide future HIV policies in Bangladesh.