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Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries.

ABSTRACT: The use of the NNRTI rilpivirine in low- and middle-income countries (LMICs) is under debate. The main objective of this study was to provide further clinical insights and biochemical evidence on the usefulness of rilpivirine in LMICs.Rilpivirine resistance was assessed in 5340 therapy-naive and 13,750 first-generation NNRTI-failed patients from Europe and therapy-naive HIV-1 subtype C (HIV-1C)-infected individuals from India (n = 617) and Ethiopia (n = 127). Rilpivirine inhibition and binding affinity assays were performed using patient-derived HIV-1C reverse transcriptases (RTs).Primary rilpivirine resistance was rare, but the proportion of patients with >100,000 HIV-1 RNA copies/mL pre-ART was high in patients from India and Ethiopia, limiting the usefulness of rilpivirine as a first-line drug in LMICs. In patients failing first-line NNRTI treatments, cross-resistance patterns suggested that 73% of the patients could benefit from switching to rilpivirine-based therapy. In vitro inhibition assays showed ? 2-fold higher rilpivirine IC50 for HIV-1C RT than HIV-1B RT. Pre-steady-state determination of rilpivirine-binding affinities revealed 3.7-fold lower rilpivirine binding to HIV-1C than HIV-1B RT. Structural analysis indicated that naturally occurring polymorphisms close to the NNRTI-binding pocket may reduce rilpivirine binding, leading to lower susceptibility of HIV-1C to rilpivirine.Our clinical and biochemical findings indicate that the usefulness of rilpivirine has limitations in HIV-1C-dominated epidemics in LMICs, but the drug could still be beneficial in patients failing first-line therapy if genotypic resistance testing is performed.

SUBMITTER: Neogi U

PROVIDER: S-EPMC4710214 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries.

Neogi Ujjwal U Häggblom Amanda A Singh Kamalendra K Rogers Leonard C LC Rao Shwetha D SD Amogne Wondwossen W Schülter Eugen E Zazzi Maurizio M Arnold Eddy E Sarafianos Stefan G SG Sönnerborg Anders A

The Journal of antimicrobial chemotherapy 20151030 2

<h4>Objectives</h4>The use of the NNRTI rilpivirine in low- and middle-income countries (LMICs) is under debate. The main objective of this study was to provide further clinical insights and biochemical evidence on the usefulness of rilpivirine in LMICs.<h4>Patients and methods</h4>Rilpivirine resistance was assessed in 5340 therapy-naive and 13,750 first-generation NNRTI-failed patients from Europe and therapy-naive HIV-1 subtype C (HIV-1C)-infected individuals from India (n = 617) and Ethiopia ...[more]

PMID: 26518047

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Dataset Information

Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries.

Publications

Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries.

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