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

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

doi:10.1097/qad.0000000000002166

Abstract

Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations. Blood samples were collected from 4973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping. Major drug-resistance mutations (DRMs) and surveillance drug resistance mutations (SDRMs) associated with nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) were analyzed according to the Stanford University HIV Drug Resistance Database. Viral sequences were screened for G-to-A hypermutations. A threshold of 2% was used for hypermutation adjustment. Viral suppression was considered at HIV-1 RNA load ≤400 copies/ml. Among 4973 participants with HIV-1C sequences, ART data were available for 4927 (99%) including 3858 (78%) on ART. Among those on ART, 3435 had viral load data and 3297 (96%) were virologically suppressed. Among 1069 (22%) HIV-infected individuals not on ART, we found NRTI-associated and NNRTI-associated SDRMs were found in 1.5% (95% confidence interval [CI] 1.0-2.5%) and 2.9% (95% CI 2.0-4.2%), respectively. Of the 138 (4%) of individuals who had detectable HIV-1 RNA, we found NRTI-associated and NNRTI-associated drug resistance mutations in 16% (95% CI 10-25%) and 33% (95% CI 25-42%), respectively. We found a low prevalence of NRTI-associated and NNRTI-associated PDR-resistance mutations among residents of rural and peri-urban communities across Botswana. However, individuals on ART with detectable virus had ADR NRTI and NNRTI mutations above 15%.

Highlights

Antiretroviral therapy (ART) coverage has increased globally with over 21 million people receiving lifesaving treatment [1]
This study aimed to survey the prevalence of HIV-1 mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) among rural and peri-urban communities across Botswana
The median age at enrollment of the participants included in this analysis study was 40 years [interquartile range (IQR) 33–47] and 72% were women

Summary

Introduction

Antiretroviral therapy (ART) coverage has increased globally with over 21 million people receiving lifesaving treatment [1]. Many countries have adopted the WHO recommendation to initiate ART in all HIV-infected individuals [3] regardless of CD4þ T-cell count. A successful scale-up of ART has been associated with an increase in pretreatment drug resistance (PDR) in low-resource settings [4]. A recent meta-analysis across 63 countries [4] revealed overall increase (up to 23% in Southern Africa) of PDR to NNRTIs. Drugresistant HIV strains limit treatment options, presenting a threat to effective scale-up of ART and getting HIV infection under control by 2030 [6]. Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations

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