Trend of Pre-antiretroviral Therapy HIV-1 Drug Resistance in Kilombero and Ulanga Antiretroviral Cohort, South-Western Tanzania, for over 15 years (2005-2020)
| dc.contributor.author | Ntamatungiro, Alex | |
| dc.contributor.supervisor | Kagura, Juliana | |
| dc.date.accessioned | 2024-12-10T07:59:51Z | |
| dc.date.available | 2024-12-10T07:59:51Z | |
| dc.date.issued | 2024 | |
| dc.description | A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, 2024 | |
| dc.description.abstract | Introduction Pre-treatment HIV drug-resistance (PDR) may result in increased risk of virological failure and subsequently acquisition of new HIV drug resistant mutations. With recent increase in antiretroviral therapy (ART) coverage and periodic modifications of the guidelines for HIV treatment, monitoring changes in levels of PDR is critical, particularly in under-sampled areas, such as rural Tanzania. This PhD project aimed to determine the trend and patterns of PDR in the Kilombero and Ulanga antiretroviral cohort (KIULARCO), analyse the impact of recent HIV-1 infection, and dolutegravir rollout in rural Tanzania. Methods The study comprised a systematic review and meta-analysis of primary studies about prevalence of PDR among ART-naive people living with HIV (PLHIV) (³15 years old), published between 2017 and 2022. The data had to be in one or several of the countries of Eastern Africa, namely, Ethiopia, Kenya, Malawi, Rwanda, Mozambique, Tanzania, and Uganda. Thereafter, cross- sectional analyses of data on newly HIV-1-diagnosed ART-naïve adults (aged ≥ 15 years), enrolled in the on-going prospective clinic-based observational rural antiretroviral cohort- KIULARCO focusing on various aspects of PDR. Multivariate logistic regressions were used to determine the factors associated with recent HIV-1 infection, and viral suppression at 12-months in patients initiating dolutegravir-based ART in the KIULARCO. Results Overall, the pooled prevalence estimate of any PDR was 10.0% (95% CI: 7.9%–12.0%, I2 =88.9%) among 22 studies in the general adults’ population, which was higher than the previously reported prevalence of 8.7% using data available until 2016 in the Eastern Africa region. PDR was mainly driven by non-nucleoside reverse transcriptase inhibitors (NNRTI); whereas the pooled prevalence of PDR to nucleoside reverse transcriptase inhibitors (NRTI) was 2.6% (95% CI: 1.8%–3.4%, I2=69.2%). Remarkably, PDR to NRTIs in a sub-population of recently HIV-1 infected PLHIV in the KIULARCO was high at 12.5%. Also, there was a notable tendency to an increasing prevalence of PDR to NRTI, with the overall prevalence of 2.1% in the first five-year period (2005-2009) of the ART program in Tanzania, and 3.4 % in the most recent period (2019-2022). Moreover, there was no PDR to the dolutegravir co-administered NRTI in those with viremia ≥50 copies/mL, at one year, in patients initiating dolutegravir-based ART in the KIULARCO 2 years after dolutegravir roll. Notably, dolutegravir-based ART was associated with >2 times the odds of viral suppression compared to NNRTI-based ART with an adjusted odds ratio (aOR) of 2.10 (95% CI 1.12-3.94). Conclusions There is notable level of PDR to NRTI among general adults’ population in Eastern Africa region, that was high among recently HIV-1 infected PLHIV in a representative rural Sub-Saharan Africa setting. Hence, routine surveillance of pre-existing resistance to the DTG co-administered NRTI remains particularly important, in resource-limited settings, to prevent risk of failure of newer antiretroviral agents such as dolutegravir, which would be detrimental to Tanzania and other low- and middle-income countries for the aim to “end AIDS by 2030”. Our results underline the benefit of programmatic uptake of dolutegravir -based ART in low- and middle-income countries. | |
| dc.description.submitter | MM2024 | |
| dc.faculty | Faculty of Health Sciences | |
| dc.identifier | https://orcid.org/ 0000-0002-3134-3992 | |
| dc.identifier.citation | Ntamatungiro, Alex. (2024). Trend of Pre-antiretroviral Therapy HIV-1 Drug Resistance in Kilombero and Ulanga Antiretroviral Cohort, South-Western Tanzania, for over 15 years (2005-2020) [PhD thesis, University of the Witwatersrand, Johannesburg]. WireDSpace. | |
| dc.identifier.uri | https://hdl.handle.net/10539/43227 | |
| dc.language.iso | en | |
| dc.publisher | University of the Witwatersrand, Johannesburg | |
| dc.rights | © 2024 University of the Witwatersrand, Johannesburg. All rights reserved. The copyright in this work vests in the University of the Witwatersrand, Johannesburg. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of University of the Witwatersrand, Johannesburg. | |
| dc.rights.holder | University of the Witwatersrand, Johannesburg | |
| dc.school | School of Public Health | |
| dc.subject | HIV-1 | |
| dc.subject | Pre-treatment HIV-1 drug resistance | |
| dc.subject | Nucleoside/ Nucleotide Reverse-Transcriptase Inhibitor | |
| dc.subject | Antiretroviral Therapy | |
| dc.subject | Low- and middle-income countries | |
| dc.subject | Tanzania | |
| dc.subject | UCTD | |
| dc.subject.other | SDG-3: Good health and well-being | |
| dc.title | Trend of Pre-antiretroviral Therapy HIV-1 Drug Resistance in Kilombero and Ulanga Antiretroviral Cohort, South-Western Tanzania, for over 15 years (2005-2020) | |
| dc.type | Dissertation |