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Clinical and HIV determinants of antiretroviral therapy response in a Nigerian subtype G/CRF02_AG epidemic

El Bouzidi, Kate; (2022) Clinical and HIV determinants of antiretroviral therapy response in a Nigerian subtype G/CRF02_AG epidemic. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Understanding the correlates of treatment failure during second-line antiretroviral therapy (ART) could inform interventions to improve outcomes among people living with HIV (PLHIV). A retrospective cohort study of PLHIV who started second-line ART at a tertiary centre in Nigeria, 2005-2017, used Kaplan-Meier estimates and Cox proportional hazards models to investigate factors associated with: virological failure (HIV-1 RNA >1,000 copies/mL), immunological failure (CD4 count decrease or <100 cells/mm3 ), and severe weight loss (>10% of bodyweight). Whole HIV-1 genome sequences were generated with Illumina MiSeq from available first-line and second-line virological failure samples. Mutations detected at ≥2% frequency were analysed and intrahost changes were observed within longitudinal viral populations. Among 1,031 cohort participants, 33% disengaged from care during a median follow-up of 6.9 years (interquartile range 3.7-8.5). Of these, 26% subsequently re-entered care. Disengagement was associated with male gender, age <30, lower education level and low CD4 count. Among participants with endpoint assessments available, 20% (112/565) experienced virological failure, 32% (257/809) experienced immunological failure, and 23% (190/831) experienced weight loss. A lower risk of virological failure was associated with professional occupations compared to elementary: adjusted hazard ratio 0.17 (95% confidence interval 0.04-0.70). There was extensive subtype variation and drug resistance at first-line ART failure in the 101 participants sampled. Major protease mutations at second-line failure were detected in 45% (18/40), and were associated with therapeutic PI levels and an increased rate of emergent gag mutations. There was also a high prevalence of protease and gag variants in West African subtypes, prior to PI exposure. Most future therapeutic options were predicted to be effective, with the exception of newer NNRTIs. In summary, adverse outcomes were common during second-line ART. Resources should be allocated to promote engagement in care and provide routine virological monitoring to target adherence interventions and inform the need for third-line regimens.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Clinical and HIV determinants of antiretroviral therapy response in a Nigerian subtype G/CRF02_AG epidemic
Language: English
Additional information: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10145899
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