2 research outputs found

    Low Prevalence of Pre-Treatment and Acquired Drug Resistance to Dolutegravir among Treatment Naïve Individuals Initiating on Tenofovir, Lamivudine and Dolutegravir in Zimbabwe

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    Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log10 VL were 39 (29–48) years and 5.41 (4.80–5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25–30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa

    HIV-1 Genetic Diversity and Natural Polymorphisms of the Integrase Gene in Integrase Inhibitor-Naive Patients in Harare, Zimbabwe.

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    Previously used as part of salvage therapy, integrase strand transfer inhibitors (INSTIs) have become part of the preferred antiretroviral therapy (ART) first-line regimen in most low- to middle-income countries. With the extensive use of dolutegravir in first-line ART, drug resistance mutations to INSTIs are inevitable. Therefore, active monitoring and surveillance of INSTI drug resistance is required. The aim of this study was to evaluate the genetic diversity of the integrase gene and determine pretreatment INSTI resistance in Harare, Zimbabwe. Forty-four HIV-1 Integrase sequences from 65 were obtained from treatment-naive individuals using a custom genotyping method. Drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program. Viral subtyping was done by phylogenetic analysis and the REGA HIV subtyping tool determined recombinants. Natural polymorphisms were evaluated relative to the global subtype B and C consensus sequences. One hundred ninety-two sequences from the region were accessed from GenBank to assess differences between the Zimbabwean sequences and those from neighboring countries. No major INSTI resistance mutations were detected; however, the L74I polymorphism was detected in three sequences of the 44 (6.8%). There was little genetic variability in the Integrase gene, with a mean genetic distance range of 0.053015. The subtype C consensus was identical to the global subtype C consensus and varied from the global subtype B consensus at five major positions: T124A, V201I, T218I, D278A, and S283G. This study has provided baseline sequence data on the presence of HIV-1 subtype C Integrase gene drug resistance mutations from Harare, Zimbabwe