Drug Resistance Mutations in a Population Before Antiretroviral Therapy Initiation in Northern South Africa

Ogola, Bixa; Matume, Nontokozo D.; Mavhandu-Ramarumo, Lufuno G; Tebit, Denis M.

doi:10.1089/aid.2021.0026

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Additional articles were identified by experts in the field. We screened out 1330 studies after removing duplicates, and 140 articles were downloaded for full-length screening, of which 39 articles were kept [ 6 , 17 , 24 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Resultsmentioning

confidence: 99%

HIV-1 Drug Resistance Detected by Next-Generation Sequencing among ART-Naïve Individuals: A Systematic Review and Meta-Analysis

Ouyang,

Yuan,

Zhai

et al. 2024

Viruses

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Background: There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques. Methods: For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the ‘meta’ package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS. Results: A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58–2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations. Conclusion: In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS.

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Section: Resultsmentioning

confidence: 99%

HIV-1 Drug Resistance Detected by Next-Generation Sequencing among ART-Naïve Individuals: A Systematic Review and Meta-Analysis

Ouyang,

Yuan,

Zhai

et al. 2024

Viruses

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“…Against a backdrop of low HIV disclosure levels [10][11][12] , worrisome levels of resistance to antiretroviral therapy (ART) [13][14][15] , and the largest HIV epidemic in the world 16 , there is an urgent need for the rapid uptake of the U=U message in South Africa. While seven African countries met the 90-90-90 targets 17 , South Africa was not one of them.…”

Section: Introductionmentioning

confidence: 99%

Associations between exposure to the U=U message and perceived HIV stigma among both the HIV and non-HIV adult populations in South Africa

Kubheka,

Patel,

Ramothwala

et al. 2024

Popul. Med.

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INTRODUCTION HIV stigma is a major barrier to care in South Africa, the country with the world's largest HIV epidemic. The educational message 'Undetectable Equals Untransmittable' (U=U) may mitigate stigma. We examined the percentage of South African adults believing the U=U message and the associations with perceived stigma. METHODS We analyzed data of South Africans aged ≥18 years from two sources: 1) The 2017-2018 South African National HIV Prevalence, Incidence, Behavior and Communication Survey (n=26875). HIV status was ascertained using both laboratory confirmation and self-reports. U=U belief was an affirmative response to the statement 'the risk of HIV transmission through sex can be reduced by an HIV-positive partner consistently taking drugs that treat HIV'; and 2) The 2019 Positive Perspectives Study of people living with HIV (PLHIV) on treatment (n=179) was analyzed to describe provider-administered U=U counseling. Data were analyzed using descriptive and multivariable approaches (p<0.05). RESULTS Overall, 20.0% of South African adults aged ≥18

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Immunologic, virologic and drug resistance outcomes in an HIV-infected prospective cohort on treatment in South Africa

Ogola,

Matume,

Tebit

et al. 2024

PLoS ONE

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Background In September 2016, South Africa introduced the Universal Test and Treat (UTT) programme to manage HIV infection. However, the development of drug resistance and sustaining viral suppression are challenges to the success of treatment programmes. This prospective observational study describes virologic, immunologic, and drug resistance profiles in a test and treat cohort in north-eastern South Africa. Methods Five hundred and thirty-four HIV-1 positive antiretroviral naïve adults entering treatment programmes were enrolled between January 2016 and February 2018. Trends in CD4+ cell count, viral load, and drug resistance by examination of deep sequences were assessed at baseline and every three months, for 24 months. Results Seventy-five percent were late initiators into ART (that is baseline CD4+ cell counts < 500 cells/microliter) and 16% were early initiators into ART and baseline CD4 was not available for 9%. Eleven percent (12/104) achieved immunological response after 6 months, 39.4% (41 /104) after 12 months, and 97.5% (101/104) after 24 months. Seventy-one percent (381/534) had baseline viral loads >1000 RNA copies/ml. Nine percent (22/246) achieved viral suppression after 3 months, 50% (122/246) after 6 months and 73.6% (181/246) after 12 months. A slower viral suppression was observed for males than females (p value = 0.012). A total of 45.6% (52/114) individuals had at least one drug resistance mutation (DRM) detected at >20% threshold in any of the time points, and the number increased to 55% (63/114) when minor variants were accounted for. Forty-eight percent (14/29) had drug resistance mutations at >5% threshold as early as 3 months into treatment. Conclusion The UNAIDS target of 95% viral suppression in individuals under treatment was not observed after 12 months of treatment, and this was less successful for males. Adherence and drug resistance monitoring could be beneficial for individuals harbouring resistant viruses early into treatment.

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Drug Resistance Mutations in a Population Before Antiretroviral Therapy Initiation in Northern South Africa

Cited by 3 publications

References 36 publications

HIV-1 Drug Resistance Detected by Next-Generation Sequencing among ART-Naïve Individuals: A Systematic Review and Meta-Analysis

HIV-1 Drug Resistance Detected by Next-Generation Sequencing among ART-Naïve Individuals: A Systematic Review and Meta-Analysis

Associations between exposure to the U=U message and perceived HIV stigma among both the HIV and non-HIV adult populations in South Africa

Immunologic, virologic and drug resistance outcomes in an HIV-infected prospective cohort on treatment in South Africa

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