High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort.

Rachel Willim,Elnaz Shadabi,Robert Balshaw,Raghavan Sampathkumar,Ma Luo,Francis A Plummer,Binhua Liang,Lin Li,Joshua Kimani

doi:10.3390/v14020273

Abstract

Background: We analyzed the prevalence of pre-antiretroviral therapy (ART) drug resistance mutations (DRMs) in a Kenyan population. We also examined whether host HLA class I genes influence the development of pre-ART DRMs. Methods: The HIV-1 proviral DNAs were amplified from blood samples of 266 ART-naïve women from the Pumwani Sex Worker cohort of Nairobi, Kenya using a nested PCR method. The amplified HIV genomes were sequenced using next-generation sequencing technology. The prevalence of pre-ART DRMs was investigated. Correlation studies were performed between HLA class I alleles and HIV-1 DRMs. Results: Ninety-eight percent of participants had at least one DRM, while 38% had at least one WHO surveillance DRM. M184I was the most prevalent clinically important variant, seen in 37% of participants. The DRMs conferring resistance to one or more integrase strand transfer inhibitors were also found in up to 10% of participants. Eighteen potentially relevant (p < 0.05) positive correlations were found between HLA class 1 alleles and HIV drug-resistant variants. Conclusions: High levels of HIV drug resistance were found in all classes of antiretroviral drugs included in the current first-line ART regimens in Africa. The development of DRMs may be influenced by host HLA class I-restricted immunity.

Highlights

Human immunodeficiency virus 1 (HIV-1) continues to be a major global health threat, with an estimated 37.6 million people living with HIV (PLWH) as of 2020 [1]
Ant, 38% of participants harbored at least one World Health Organization (WHO) surveillance DRM (SDRM), and 42% had at least level resistance drug resistance mutations (DRMs) to one of the first-line medications used in Kenya [28]
This compared with previous studies reporting TDR prevalence of 8% in men who h with men (MSM) in Coastal Kenya from 2005 to 2017 [29], SDRM prevalence of four African countries from 2013 to 2019 [31], pre-treatment DRM prevalence of rural Kenya from 2008 to 2013 [32], and a 9.7% SDRM prevalence in Nigeria from

Summary

Introduction

Human immunodeficiency virus 1 (HIV-1) continues to be a major global health threat, with an estimated 37.6 million people living with HIV (PLWH) as of 2020 [1]. The 90–90–90 target was not reached, the attempt led to unified efforts to increase testing, diagnosis, as well as effective treatment of PLWH [1]. These global efforts are necessary to reach the UNAIDS sustainable development goal—95–95–95 by 2030 [3,4]. The results of large studies on sexual transmission of HIV in thousands of serodiscordant couples showed that “individuals living with HIV who have an undetectable level of virus in their blood due to ART are unable to transmit the virus to others” [6,7,8]. Results: Ninety-eight percent of participants had at least one DRM, while 38% had at least one WHO surveillance DRM

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Conclusion