Project Title

Monitoring of HIV drug resistance in South Africa and innovative approaches to HIV drug resistance testing (HIVDR-MIT)

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

1: To design a method for detecting HIVDR mutations in the PR, RT and IN genes 2: To develop a database for monitoring cases of HIVDR in KwaZulu-Natal 3: To use the database knowledge to inform the provincial public health response to HIV

Project Summary

The overall objectives of this work are to i) design a method for detecting HIVDR mutations in the PR, RT and IN genes, ii) to develop a database for monitoring cases of HIVDR in KwaZulu-Natal, and iii) to use the database knowledge to inform the provincial public health response to HIV. From the first objective, we successfully optimized and designed a simple, timely, innovative and cost-effective method for detecting HIVDR mutations in the HIV-1 protease (PR), reverse transcriptase (RT) and integrase (IN) genes. In summary, we processed 96 samples, and obtained sequence data for 78 (81%), of which 75 (96%) had a least one HIVDR mutation, with no major-IN mutations observed. When compared to previous genotypes, only 2 of 78 (3%) sequences had different phenotypic predictions that affected choice of subsequent regimen. Seven EQA samples were processed for validation, 4 of which were HIV-1C, 2 were HIV-1D, and 1 was HIV-1A, showing successful genotyping of different HIV-1 subtypes. HIVDR resistance results obtained using the IDR method were 100% concordant with EQA panel results. Overall genotyping cost per sample was estimated at ~US$43, with a processing time of ~2 working days. Therefore, we successfully completed the first objective of this study. For the second objective, we set up and conducted analysis of HIV-1 drug resistance data generated from routine tests, at provincial level in KwaZulu-Natal (KZN) province, South Africa, for the period January 2018 – August 2020. Routine HIVDR test results from the National Health Laboratory Service (NHLS) Department of Virology (DoV) in Durban, South Africa, were obtained and uploaded into an HIVDR database designed using PowerBI, a business analytics service by Microsoft. Of 2148 HIVDR genotypes, six in every seven (1846) had at least one HIVDR mutation. The prevalence of HIVDR ranged from 76% - 96% among the 11 districts in KZN. Only 5 had any DTG-associated resistance mutations detected. The majority of genotypes obtained were from females (59.2%) and a small proportion of them were from children (10.2%) aged <20 years. Genotypes done prior to DTG-rollout (i.e. December 2019) had a 1.30-fold (95% CI 0.99–1.71, p=0.08) higher odds of having HIVDR mutations, and the proportions of HIVDR mutations were significantly higher among adult females (≥20 years), p=0.04. Notably, protease inhibitor and nucleoside reverse transcriptase inhibitor mutations were significantly decreased between pre- and post- DTG-rollout, p<0.05. The minimal DTG-associated resistance and overall reduction in HIVDR mutations suggests effective use of DTG-based ART in KZN clinical settings. HIVDR hotspots were observed in densely populated urban and peri-urban districts, and adult women had higher proportions of HIVDR. These preliminary data show how near-real time HIVDR monitoring through databasing can be used to inform optimization of HIV-1 treatment at public-health level. More data is being curated to cover more recent years of the HIV treatment program. For the third objective, this work provides insight into populations requiring targeted prevention and treatment services, and assists policy makers in tracking the burden of HIVDR in KZN province, whilst also providing relevant data to scientists and researchers involved in the response to HIV-1, without having to perform additional studies that can have a huge economic impact. This work is also training postgraduate students in specialized fields of virology. Therefore, this ongoing project is helping inform public-health response to HIV-1 treatment, whilst providing dynamic tools that are streamlined to detect and monitor HIVDR and treatment outcomes resulting from changes in ART guidelines. This has an ultimate benefit in reducing the HIV-1 burden in society, as we work towards achieving the UNAIDS 95-95-95 goals, which target eliminating HIV by 2030.

Host Organisation

Results & Outcomes

Current Organisation

CAPRISA and U.S. NIH

Current Job Title

Research Fellow

Biography

Publications