Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana

Bareng, Ontlametse T.; Seselamarumo, Sekgabo; Seatla, Kaelo K; Choga, Wonderful T.; Bakae, Blessing; Maruapula, Dorcas; Kelentse, Nametso; Moraka, Natasha O.; Mokaleng, Baitshepi; Mokgethi, Patrick; Ditlhako, Tsotlhe; Pretorius-Holme, Molly; Mbulawa, Mpaphi B.; Lebelonyane, Refeletswe; Bile, Ebi C; Gaolathe, Tendani; Shapiro, Roger; Makhema, Joseph; Lockman, Shahin; Essex, Max; Novitsky, Vlad; Mpoloka, Sununguko Wata; Moyo, Sikhulile; Gaseitsiwe, Simani

doi:10.1016/j.jgar.2022.08.008

Cited by 2 publications

(2 citation statements)

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“…We report high HIV-1 ADR and PDR prevalence among non-citizens living with HIV-1 in Botswana. However, according to some studies done in Botswana, (Moyo et al, 2019), a low prevalence of PDR was reported where the prevalence of NRTI-associated or NNRTI-associated DRMs among these individuals was 15.9 and 32.6%, respectively (Moyo et al, 2019;Maruapula et al, 2022). The majority of the study participants were from Zimbabwe (Migrantrefugees, 2023).…”

Section: Discussionmentioning

confidence: 93%

“…Using in-house genotypic resistance testing ( Seatla et al, 2019 ; Bareng et al, 2022 ), the extracted RNA was amplified by nested Polymerase chain reaction (PCR) to obtain the HIV-1 pol which comprised the entire protease (PR) gene (codons 1-99) and reverse transcriptase (RT) gene (codons 1-560). The RT-PCR was done using the following primers ( Rowley et al, 2016 ; Bareng et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

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High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana

Mokgethi,

Choga,

Maruapula

et al. 2024

Front. Microbiol.

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BackgroundApproximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana.MethodsA total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019–2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the pol region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups.ResultsA total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38–48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate – 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12–0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported.ConclusionWe report high rates of PDR and ADR in ART-experienced and ART-naïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV-1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success.

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Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana

Mokgethi,

Choga,

Maruapula

et al. 2024

Front. Microbiol.

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Genetic Diversity and Drug Resistance Mutations in HIV-1 pol Gene Sequences in the Philippines: A Retrospective Genomic Analysis

Reyes,

Tolentino,

Castillo

et al. 2024

J. Pure Appl. Microbiol.

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The Philippines has experienced a significant increase in HIV-1 infections in recent years, with a growing epidemic driven by the CRF01_AE strain. Understanding the genetic diversity of HIV-1 in the Philippines is crucial for the development of effective treatment strategies and the prevention of drug resistance. This study analyzed comprehensive data on common resistance mutation patterns from 2009 to 2017, revealing an increasing trend of mutations observed in NRTI and NNRTI resistance among the predominant CRF01_AE strains. The most common NRTI mutations observed were M184V, K65R, and S68G, whereas the most common NNRTI mutations were K103N, Y181C, and G190A. The study also found a high prevalence of M184V minority variants (0.5-20%) in treatment-naive patients, which could increase the risk of virological failure in 3TC-containing regimens. The findings of this study highlight the importance of comprehensive drug resistance surveillance and access to resistance testing to guide optimal first-line antiretroviral treatment selection and to manage the growing HIV-1 epidemic in the Philippines. The development of effective strategies to prevent and manage drug resistance is crucial to ensuring the long-term success of HIV treatment programs in the country.

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Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana

Cited by 2 publications

References 30 publications

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana

Genetic Diversity and Drug Resistance Mutations in HIV-1 pol Gene Sequences in the Philippines: A Retrospective Genomic Analysis

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