<scp>HIV</scp> drug resistance levels in adults failing first‐line antiretroviral therapy in an urban and a rural setting in <scp>S</scp>outh <scp>A</scp>frica

Rossouw, Theresa M.; Nieuwoudt, Martin; Manasa, Justen; Malherbe, G. P.; Lessells, Richard J; Pillay, Sandy; Danaviah, Siva; Mahasha, Phetole Walter; Dyk, Gisela Van; Oliveira, Túlio de

doi:10.1111/hiv.12400

Cited by 25 publications

(30 citation statements)

References 45 publications

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“…M184V, the most common NRTI RAM, occurred more frequently in patients receiving AZT plus 3TC, in comparison with patients receiving the ABC plus 3TC regimen. Our findings correspond with previous studies conducted in South Africa with PLHIV, showing M184V/I as the most prevalent NRTI mutation (Marconi et al, 2008;Van Zyl et al, 2011Wallis et al, 2011;Lombaard et al, 2016;Neogi et al, 2016;Steegen et al, 2016a,b;Rossouw et al, 2017;Penrose et al, 2018). The K65R and Y115F RAMs occurred more frequently in patients receiving AZT plus 3TC, rather than in patients receiving ABC plus 3TC.…”

Section: Discussionsupporting

confidence: 92%

Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa

et al. 2020

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The South African national combination antiretroviral therapy (cART) roll-out program started in 2006, with over 4.4 million people accessing treatment since it was first introduced. HIV-1 drug resistance can hamper the success of cART. This study determined the patterns of HIV-1 drug-resistance associated mutations (RAMs) in People Living with HIV-1 (PLHIV-1). Receiving first (for children below 3 years of age) and second-line (for adults) cART regimens in South Africa. During 2017 and 2018, 110 patients plasma samples were selected, 96 samples including those of 17 children and infants were successfully analyzed. All patients were receiving a boosted protease inhibitor (bPI) as part of their cART regimen. The viral sequences were analyzed for RAMs through genotypic resistance testing. We performed genotypic resistance testing (GRT) for Protease inhibitors (PIs), Reverse transcriptase inhibitors (RTIs) and Integrase strand transfer inhibitors (InSTIs). Viral sequences were subtyped using REGAv3 and COMET. Based on the PR/RT sequences, HIV-1 subtypes were classified as 95 (99%) HIV-1 subtype C (HIV-1C) while one sample as 02_AG. Integrase sequencing was successful for 89 sequences, and all the sequences were classified as HIV-1C (99%, 88/89) except one sequence classified CRF02_AG, as observed in PR/RT. Of the 96 PR/RT sequences analyzed, M184V/I (52/96; 54%) had the most frequent RAM nucleoside reverse transcriptase inhibitor (NRTI). The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%). Protease inhibitor (PI) RAMs M46I and V82A were present in 12 (13%) of the sequences analyzed. Among the InSTI major RAM two (2.2%) sequences have Y143R and T97A mutations

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Section: Discussionsupporting

confidence: 92%

Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa

et al. 2020

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“…In South Africa, findings of the National HIV Prevalence, Incidence, Behaviour and Communication Survey 2017 similarly estimated that 89.9 and 82.1% of females and males on ART were virally suppressed [14]. Less is known about prevalence of viral suppression in the general population, particularly in rural areas, where monitoring is less consistent [15]. One population-based study covering 32 rural Kenyan and Ugandan communities noted that 45% of HIV-positive individuals had evidence of viral suppression prior to intensive interventions to improve ART initiation [16].…”

Section: Introductionmentioning

confidence: 99%

“…Understanding factors driving virological failure, including the contribution of both pre-treatment drug resistance and acquired resistance, is critical to ensuring treatment remains effective and that existing first-line regimens can be preserved. Data are scarce on the prevalence of genotypic resistance in rural areas of Sub-Saharan Africa [15] and rarely is genotypic resistance data available from population-based sampling, coincident with both reported adherence and known ART exposure.…”

Section: Introductionmentioning

confidence: 99%

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study

et al. 2020

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Background: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. Methods:We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design.Results: Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens.Conclusions: DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

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“…To date, PANGEA has generated over 18 000 NGS HIV sequences from five countries in sub-Saharan Africa, from diverse settings including cohorts of the population-based cohorts from surveillance sites (Rakai Community Cohort Study) [18 && ], the Mochudi Prevention Project [19,20], the MRC/UVRI Uganda population-based cohorts, and fisherfolk cohorts [21][22][23] an MRC/UVRI Uganda cohort of female sex-workers [24], a cohort of HIV-1 drug-resistant individuals from northern KwaZulu-Natal in South Africa (Africa Health Research Institute Resistance Cohort) [25], participants from the Partners in Prevention HSV/HIV Transmission Study [26], and participants from the TasP trial [27]. Data from the HPTN 071-2 (PopART) trial Phylogenetics ancillary study [28] will become available in spring 2020.…”

Section: Introductionmentioning

confidence: 99%

Pangea-Hiv 2

Abeler-Dörner

Grabowski

Rambaut

et al. 2019

Current Opinion in HIV and AIDS

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HIV drug resistance levels in adults failing first‐line antiretroviral therapy in an urban and a rural setting in South Africa

Cited by 25 publications

References 45 publications

Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa

Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study

Pangea-Hiv 2

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