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Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

ABSTRACT: OBJECTIVES:To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. METHODS:We conducted a case-control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ?1000 RNA copies/mL after ?6?months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ?20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. RESULTS:We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ?20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P?=?0.210. Participants with PDR at ?20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8-18.3) compared with those without, P?=?0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ?2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6-4.3) compared with those without, P?=?0.398. CONCLUSIONS:Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions.

SUBMITTER: Chimukangara B

PROVIDER: S-EPMC7566390 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

Chimukangara Benjamin B Giandhari Jennifer J Lessells Richard R Yende-Zuma Nonhlanhla N Sartorius Benn B Samuel Reshmi R Khanyile Khulekani S KS Stray-Pedersen Babill B Moodley Pravi P Metzner Karin J KJ Padayatchi Nesri N Naidoo Kogieleum K De Oliveira Tulio T

The Journal of antimicrobial chemotherapy 20201101 11

<h4>Objectives</h4>To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART.<h4>Methods</h4>We conducted a case-control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq nex ...[more]

PMID: 32772079

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Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

Publications

Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

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