Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana

Moyo, Sikhulile; Gaseitsiwe, Simani; Zahralban-Steele, Melissa; Maruapula, Dorcas; Nkhisang, Tapiwa; Mokaleng, Baitshepi; Mohammed, Terence; Ditlhako, Tsotlhe; Bareng, Ontlametse T.; Mokgethi, Thatayaone P.; Widenfelt, Erik van; Pretorius-Holme, Molly; Mine, Madisa; Raizes, Elliot; Yankinda, Etienne Kadima; Wirth, Kathleen; Gaolathe, Tendani; Makhema, Joseph; Lockman, Shahin; Essex, Max; Novitsky, Vlad

doi:10.1097/qad.0000000000002166

Cited by 13 publications

(12 citation statements)

References 27 publications

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“…[53][54][55] A similar finding was also reported in a study conducted in Botswana that used samples with undetectable VLs to determine the prevalence of DRMs. [56] In our study, two samples with VLs of <40 copies/mL were successfully sequenced by Sanger sequencing and NGS. Participants were divided into two groups depending on whether they had low-frequency DRMs.…”

Section: Discussionmentioning

confidence: 99%

Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana

et al. 2022

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Background: Individuals living with human immunodeficiency virus (HIV) who experience virological failure (VF) after combination antiretroviral therapy (cART) initiation may have had low-frequency drug resistance mutations (DRMs) at cART initiation. There are no data on low-frequency DRMs among cART-naïve HIV-positive individuals in Botswana.Methods: We evaluated the prevalence of low-frequency DRMs among cART-naïve individuals previously sequenced using Sanger sequencing. The generated pol amplicons were sequenced by next-generation sequencing.Results: We observed low-frequency DRMs (detected at <20% in 33/103 (32%) of the successfully sequenced individuals, of whom four also had mutations detected at >20%. K65R was the most common low-frequency DRM detected in 8 individuals. Eighty-two of the 103 individuals had follow-up viral load data while on cART. Twenty-seven of the 82 individuals harbored lowfrequency DRMs. Only 12 of 82 individuals experienced VF. The following low-frequency DRMs were observed in four individuals experiencing VF: K65R, K103N, V108I, and Y188C. No statistically significant difference was observed in the prevalence of lowfrequency DRMs between individuals experiencing VF (4/12) and those not experiencing VF (23/70) (P = .97). However, individuals with non-nucleoside reverse transcriptase inhibitors-associated low-frequency DRMs were 2.68 times more likely to experience VF (odds ratio, 2.68; 95% confidential interval, 0.4-13.9) compared with those without (P = .22). Conclusion:Next-generation sequencing was able to detect low-frequency DRMs in this cohort in Botswana, but these DRMs did not contribute significantly to VF. Abbreviations: ANCs = antenatal clinics, BHP = Botswana Harvard AIDS Partnership, cART = combination antiretroviral therapy, DRMs = drug resistance mutations, DTG = dolutegravir, EFV = efavirenz, FTC = emtricitabine, HIV = human immunodeficiency virus, IDCC = infectious disease care clinics, KRISP = Kwazulu-Natal Research Innovation and Sequencing Platform, NGS = next generation sequencing, NNRTI = non-nucleoside reverse transcriptase inhibitors, NRTI = nucleoside reverse transcriptase inhitors, OR = odds ratio, PASeq = polymorphism analysis sequencing, PCR = polymerase chain reaction, PI = protease inhibitors, PR = protease, RNA = ribonucleic acid, RT = reverse transcriptase, TB = tuberculosis, TDF = tenofovir disoproxil fumarate, VF = virological failure, VL = viral load.

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Section: Discussionmentioning

confidence: 99%

Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana

et al. 2022

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“…These findings were concordant with our previous study that reported no association between VL and DRM in the same cohort, although the DRMs were detected in proviral DNA. 44 Most studies have reported concordance in DRM detected in both viral RNA and proviral DNA; 45,46 therefore both can be useful in LLV for the detection of DRM.…”

Section: Discussionmentioning

confidence: 98%

HIV-1C in-House RNA-Based Genotyping Assay for Detection of Drug Resistance Mutations in Samples with Low-Level Viral Loads

Bareng¹,

Choga²,

Maphorisa

et al. 2022

IDR

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Monitoring HIV-1 drug resistance mutations (DRM) in treated patients on combination antiretroviral therapy (cART) with a detectable HIV-1 viral load (VL) is important for the selection of appropriate cART. Currently, there is limited data on HIV DRM at low-level viremia (LLV) (VL 401-999 copies/mL) due to the use of a threshold of VL ≥1000 copies/mL for HIV DRM testing. We here assess the performance of an in-house HIV drug resistance genotyping assay using plasma for the detection of DRM at LLV. Methods: We used a total of 96 HIV plasma samples from the population-based Botswana Combination Prevention Project (BCPP). The samples were stratified by VL groups: 50 samples had LLV, defined as 401-999 copies/mL, and 46 had ≥1000 copies/mL. HIV pol (PR and RT) region was amplified and sequenced using an in-house genotyping assay with BigDye sequencing chemistry. Known HIV DRMs were identified using the Stanford HIV Drug Resistance Database. Genotyping success rate between the two groups was estimated and compared using the comparison of proportions test. Results:The overall genotyping success rate was 79% (76/96). For VL groups, the genotyping success was 72% (36/50) at LLV and 87% (40/46) at VL ≥1000 copies/mL. Among generated sequences, the overall prevalence of individuals with at least 1 major or intermediate-associated DRM was 24% (18/76). The proportions of NNRTI-, NRTI-and PI-associated resistance mutations were 28%, 24%, and 0%, respectively. The most predominant mutations detected were K103N (18%) and M184V (12%) in NNRTI-and NRTIassociated mutations, respectively. The prevalence of DRM was 17% (6/36) at LLV and 30% (12/40) at VL ≥1000 copies/mL. Conclusion:The in-house HIV genotyping assay successfully genotyped 72% of LLV samples and was able to detect 17% of DRM amongst them. Our results highlight the possibility and clinical significance of genotyping HIV among individuals with LLV.

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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 ( Migrant-refugees, 2023 ).…”

Section: Discussionmentioning

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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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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Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana

Abstract: Supplemental Digital Content is available in the text

Cited by 13 publications

References 27 publications

Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana

Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana

HIV-1C in-House RNA-Based Genotyping Assay for Detection of Drug Resistance Mutations in Samples with Low-Level Viral Loads

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

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