Dolutegravir drug-resistance monitoring in Africa

Kouamou, Vinie; Inzaule, Seth; Manasa, Justen

doi:10.1016/s2352-3018(21)00268-x

Cited by 7 publications

(12 citation statements)

References 9 publications

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“…28 Infrequent but possible dolutegravir resistance and the restricted resistance genotyping capacities in LMICs challenge identification and clinical management of those with viral failure on a TLD regimen in routine care. Antiretroviral drug level monitoring (in blood or urine) might help to distinguish resistance from simple non-adherence and triage for drug-resistance testing, 32 although in our study both participants who were dolutegravir-resistant also had low or undetectable dolutegravir plasma levels. Development of simplified point-mutation assays could support urgently needed access to resistance testing.…”

Section: Discussionmentioning

confidence: 69%

“…32 In Malawi, by the end of December, 2021, 889 665 (99%) of 897 880 people on first-line and second-line ART were receiving a TLD regimen, and most transitioned without viral load testing (unpublished data, MoH, Department of HIV and AIDS, Malawi). Average viral load suppression rates (<1000 copies per mL) before the policy change were 93%, 32 implying that a proportion of people with an increased risk of treatment failure are present in the national treatment programme, underlining the importance of further scale-up in viral load testing and implementation of surveillance for dolutegravir resistance. Malawi hopes to provide drug-resistance testing for all people for whom the TLD regimen is failing; however, capacity and cost remain a challenge, as in most LMICs.…”

Section: Discussionmentioning

confidence: 99%

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Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study

Schramm¹,

Temfack²,

Descamps

et al. 2022

The Lancet HIV

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study

Schramm¹,

Temfack²,

Descamps

et al. 2022

The Lancet HIV

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“…In-house assays have been widely used for HIVDR genotyping especially in RLS where cost remains a major barrier. Reducing the cost of HIV-1 genotypic testing through affordable in-house assays and monitoring strategies could improve access [22], which will subsequently improve clinical decisions and treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

Affordable drug resistance genotyping of HIV-1 reverse transcriptase, protease and integrase genes, for resource limited settings

et al. 2023

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Background As use of dolutegravir (DTG) becomes more common in resource limited settings (RLS), the demand for integrase resistance testing is increasing. Affordable methods for genotyping all relevant HIV-1 pol genes (i.e., protease (PR), reverse transcriptase (RT) and integrase (IN)) are required to guide choice of future antiretroviral therapy (ART). We designed an in-house HIV-1 drug resistance (HIVDR) genotyping method that is affordable and suitable for use in RLS. Methods We obtained remnant plasma samples from CAPRISA 103 study and amplified HIV-1 PR, RT and IN genes, using an innovative PCR assay. We validated the assay using remnant plasma samples from an external quality assessment (EQA) programme. We genotyped samples by Sanger sequencing and assessed HIVDR mutations using the Stanford HIV drug resistance database. We compared drug resistance mutations with previous genotypes and calculated method cost-estimates. Results From 96 samples processed, we obtained sequence data for 78 (81%), of which 75 (96%) had a least one HIVDR mutation, with no major-IN mutations observed. Only one sample had an E157Q INSTI-accessory mutation. When compared to previous genotypes, 18/78 (23%) had at least one discordant mutation, but only 2/78 (3%) resulted in different phenotypic predictions that could affect choice of subsequent regimen. All CAPRISA 103 study sequences were HIV-1C as confirmed by phylogenetic analysis. Of the 7 EQA samples, 4 were HIV-1C, 2 were HIV-1D, and 1 was HIV-1A. Genotypic resistance data generated using the IDR method were 100% concordant with EQA panel results. Overall genotyping cost per sample was estimated at ~ US$43–$US49, with a processing time of ~ 2 working days. Conclusions We successfully designed an in-house HIVDR method that is suitable for genotyping HIV-1 PR, RT and IN genes, at an affordable cost and shorter turnaround time. This HIVDR genotyping method accommodates changes in ART regimens and will help to guide HIV-1 treatment decisions in RLS.

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“…2). Гиперчувствительность к абакавиру может возникнуть у 5-8% пациентов и требу-ет проведения генотипического скрининга, поскольку развитие таких НР может быть опасным для жизни пациента [48].…”

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“…Останавливаясь на выводах, стоит отметить, что многие АРВП подвергаются метаболизму с участием системы CYP, и большинство из них являются либо ингибиторами, либо индукторами CYP, немногие обладают способностью как ингибировать, так и индуцировать CYP или не влияют на CYP. Способность АРВП ингибировать или индуцировать активность микросомальных ферментов печени может приводить к фармакокинетическим и фармакодинамическим взаимодействиям при одновременном применении двух и более АРВП, что может повышать риск развития НР либо приводить к неэффективности фармокотерапии ВИЧ-инфекции [9,48,[68][69][70] (см. табл.…”

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Pharmacokinetic and pharmacodynamic features of antiretroviral products

Useinova

Egorova

Maryanenko

et al. 2022

VIČ-infekc. immunosupr.

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Introduction. Since the appearance of the immune deficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) at the beginning of 1980s, humanity started to understand elementary processes, underlying biology of HIV that enabled to develop safe and efficient treatment methods. Currently HIV therapy includes combined treatment regimen that allows combined drug interaction.Objective. To study the features of pharmacokinetics and pharmacodynamics, and also drug interaction of specific product groups, affecting human immunodeficiency virus.Materials and methods. Analytical review is based on analysis of literary sources of scientific database (PubMed, Cochrane Library, Сyberleninka) that contains information about peculiarities of pharmacokinetic and pharmacodynamic antiretroviral products’ interaction (ARVP) when used by HIV-infected patients for the period 1995–2022. Results and discussion. The current study enabled to summarize the research results, devoted to the issue of combined ARVP use by HIV-infected patients, and also to identify variants of irrational ARVP combination, caused by increased risk of toxicity with their simultaneous application.Conclusion. Studying the characteristics of each medical product, used in HIV infection therapy, allows to choose optimal pharmacotherapy regimens, taking into account individual patient characteristics, and also to predict and prevent the risk of adverse reactions in the future.

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Dolutegravir drug-resistance monitoring in Africa

Cited by 7 publications

References 9 publications

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study

Affordable drug resistance genotyping of HIV-1 reverse transcriptase, protease and integrase genes, for resource limited settings

Pharmacokinetic and pharmacodynamic features of antiretroviral products

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