Molecular characterization of HIV-1 subtypes and primary drug resistance mutations in Bangladesh: Insights from 2019 data

The study, "Molecular Characterization of HIV-1 Subtypes and Primary Drug Resistance Mutations in Bangladesh: Insights from 2019 Data," was carried out by Md. Maruf Ahmed Molla, Nahida Sultana, Jannat Ara Disha, Tasnim Nafisa, Mahmuda Yeasmin, Ruksana Raihan, Shahina Tabassum, and Saif Ullah Munshi in The Open AIDS Journal.

Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV) has been a significant public health concern for over four decades. Globally, more than 75 million individuals have been infected, with an estimated 32.7 million deaths attributed to AIDS-related complications. Even though there are continuous advancements in treatment and prevention, in 2019, about 1.7 million new infections were reported, which represents a 23% decline in new diagnoses compared to 2010, The high frequency of the D121 polymorphism, though not directly linked to treatment failure, reflects underlying genetic variability that may influence future resistance pathways

Why Knowing the Genetic Profile of HIV in Bangladesh Matters

Bangladesh has long been considered a low HIV-prevalence country, with infection rates remaining below 1% in the general population since the first confirmed case was diagnosed in 1989. That picture, however, is complicated by higher prevalence in key populations. Among specific high-risk groups — including men who have sex with men, people who inject drugs, female sex workers, and transgender individuals — prevalence is higher, and recent surveillance data point to a growing epidemic among returning migrant workers, with half of the 30 patients enrolled in this study reporting a history of working abroad, particularly in Saudi Arabia. Understanding exactly which strain of the virus is circulating, whether it is developing resistance to standard medications, they directly determine whether the drugs a patient is given when they first start treatment will actually work. Bangladesh has very limited data on this, with the last published sequencing study from the country relying on samples collected in 2016 and covering drug resistance analysis in only ten individuals. This study was designed using 2019 samples and approach covering both the virus's genetic subtype and its capacity to resist the two main classes of reverse transcriptase inhibitor drugs used in first-line antiretroviral therapy.

HIV-1 Subtype C — Viral genome

The research team at the Department of Virology, Bangladesh Medical University, Dhaka, enrolled 30 treatment-naive HIV-positive adults from across all eight administrative divisions of Bangladesh and performed genetic sequencing on two regions of the viral genome — the envelope gene and the reverse transcriptase gene — using validated laboratory methods and internationally recognised analytical tools. All 30 sequences were confirmed as HIV-1 subtype C, the strain that predominates across South Asia and sub-Saharan Africa and accounts for more than half of all HIV infections globally, a finding consistent with earlier Bangladeshi data. Phylogenetic analysis — which maps how closely related different viral sequences are to one another — revealed that the Bangladeshi strains clustered most strongly with viral sequences from India, China, Malaysia, Iran, Myanmar, and South Africa, reflecting the role of international labour migration in shaping the country's epidemic. Five sequences additionally showed characteristics of CRF_07BC, a circulating recombinant form of the virus more common in East and Southeast Asia, particularly China, this finding suggests potential cross-border transmission, most likely due to migration and labor movement, a conclusion bolstered by the fact that 50% of participants had a history of living abroad. No major resistance mutations against Nucleoside Reverse Transcriptase Inhibitors (NRTIs) such as tenofovir and lamivudine were detected, which means these drugs should still work effectively for patients starting treatment. However, four patients (13%) harboured resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) — specifically V106I, G190V, and V179D. Efavirenz and nevirapine, the two NNRTIs most commonly used in Bangladesh's first-line regimens, are directly affected by these mutations. The G190V mutation found in one patient confers high-level resistance to both drugs; the other two mutations, though classified as accessory, can compound resistance when present alongside other changes in the virus. Additionally, 77% of all sequences carried the D121 polymorphism — a background genetic variation whose long-term clinical significance is not yet fully understood but which may influence how drug resistance evolves under treatment pressure. Co-receptor tropism analysis, which predicts how the virus enters human immune cells, showed that 77% of sequences used the CCR5 receptor — the type typical of early-stage infection — while 23% used the CXCR4 receptor, a variant associated with faster disease progression and poorer treatment outcomes, and one that would not respond to the CCR5-blocking drug maraviroc if that were ever considered as part of a treatment plan.

Bangladesh Faces a Growing Need for Routine HIV Sequencing

The 13% rate of NNRTI resistance detected among treatment-naive patients is particularly significant in the context of global HIV policy. The World Health Organization's 2021 HIV Drug Resistance Report identified a threshold of 10% pre-treatment NNRTI resistance as the point at which national guidelines should be revised — and several countries in sub-Saharan Africa and Southeast Asia have already crossed it and updated their treatment recommendations accordingly. The 13% prevalence of NNRTI resistance in treatment-naive patients places Bangladesh above the 10% threshold., yet the country currently lacks a systematic national HIV sequencing programme outside research and academic institutions. Without routine genotyping of newly diagnosed patients, clinicians may not know whether a patient's virus carries resistance mutations before selecting first-line ART, potentially leading to treatment failure. The authors call for Bangladesh to follow the examples of countries like South Africa and Brazil, which have integrated routine HIV genotyping into their national programmes and seen measurable improvements in treatment outcomes and drug stewardship as a result. They also note that Bangladesh has begun introducing dolutegravir — a newer drug from the integrase inhibitor class with a much higher barrier to resistance than NNRTIs — into its treatment guidelines, while noting that uptake remains limited and that future studies should sequence the integrase gene to assess whether resistance to this newer class is already emerging. The authors acknowledge the study's limitations openly: the sample size of 30, though sufficient to characterise circulating strains and identify dominant subtypes in a low-prevalence setting, is small by international standards; the use of Sanger sequencing for co-receptor analysis may have underestimated the proportion of CXCR4-tropic viruses; and the protease and integrase gene regions were not covered. Larger, multi-site studies incorporating whole-genome sequencing and representation from all key affected populations are the clear next step. The research was led by corresponding author Prof. Saif Ullah Munshi, with co-authors Md. Maruf Ahmed Molla, Nahida Sultana, Tasnim Nafisa, Mahmuda Yeasmin, Ruksana Raihan, and Shahina Tabassum — all of the Department of Virology, Bangladesh Medical University, Dhaka — and Jannat Ara Disha of the Department of Medicine, National Heart Foundation Hospital and Research Institute, Dhaka.

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

DOI: 10.2174/0118746136419186260624054535

Read the published article here: https://bit.ly/4wuI7LV