Beyond clinical trials: Cross-sectional associations of combination antiretroviral therapy with reports of multiple symptoms and non-adherence among adolescents in South Africa

H P M Natukunda, L D Cluver, E Toska, V Musiime, A R Yakubovich


Background. Studies investigating symptoms associated with combination antiretroviral therapy (cART) use among adolescents in resource-limited settings are rare beyond clinical trials. Identifying adolescents at risk of non-adherence is imperative for HIV/AIDS programming and controlling the epidemic in this key population.

Objective. To examine which cART regimens were associated with reports of multiple symptoms and past-week non-adherence in a large community-traced sample of HIV-positive adolescents in South Africa (SA).

Methods. A total of 1 175 HIV-positive ART-experienced adolescents aged 10 - 19 years attending 53 health facilities in the Eastern Cape Province, SA, were interviewed in 2014 - 2015. Ninety percent (n=1 059) were included in the study. Adolescents who reported no medication use and those with unclear or missing data were excluded from further analysis, resulting in a sample for analysis of n=501. Outcomes were reports of multiple symptoms (three or more symptoms in the past 6 months) and past-week ART non-adherence (<95% correct doses in the past week). Multivariable logistic regression analyses controlled for sociodemographic and HIV-related covariates in Stata 13/IC.

Results. Of the adolescents included, 54.3% were female. The median age was 14 (interquartile range 12 - 16) years, and 66.5% were vertically infected. The prevalence of multiple symptoms was 59.7% (95% confidence interval (CI) 55.3 - 63.9). Independent of covariates, stavudine (d4T)-containing cART regimens and the fixed-dose combination of tenofovir (TDF) + emtricitabine (FTC) + efavirenz (EFV) were associated with more reports of multiple symptoms (adjusted odds ratio (aOR) 3.38; 95% CI 1.19 - 9.60 and aOR 2.67; 95% CI 1.21 - 5.88, respectively). Lopinavir/ritonavir (LPV/r)-containing regimens were associated with fewer reports of multiple symptoms (aOR 0.47; 95% CI 0.21 - 1.04). For EFV-based regimens, adolescents on d4T + lamivudine (3TC) + EFV were more likely to report multiple symptoms than those on TDF + FTC + EFV or those on abacavir (ABC) + 3TC + EFV (aOR 3.26; 95% CI 1.01 - 10.52, aOR 2.86; 95% CI 1.35 - 6.05 and aOR 1.08; 95% CI 0.64 - 1.82, respectively). However, only TDF + FTC + EFV cART was associated with lower levels of non-adherence among participants (aOR 0.44; 95% CI 0.21 - 0.93).

Conclusions. Rates of multiple symptoms among HIV-positive ART-experienced adolescents were high. d4T-containing regimens and TDF + FTC + EFV were associated with more reports of multiple symptoms, whereas LPV/r-containing regimens were associated with fewer reports. However, adolescents on TDF + FTC + EFV were the most adherent subgroup. These findings support the World Health Organization-recommended discontinuation of d4T use, but also underscore the dilemma faced by clinicians when choosing between low-toxicity regimens and those that promote ART adherence, particularly among HIV-positive adolescents.


Authors' affiliations

H P M Natukunda, Pathology Department, Medical Research Council, Harwell Institute, UK; Department of Social Policy and Intervention, University of Oxford, UK

L D Cluver, Department of Social Policy and Intervention, University of Oxford, UK; Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, South Africa

E Toska, Department of Social Policy and Intervention, University of Oxford, UK; AIDS and Society Research Unit, Centre for Social Science Research, Faculty of Humanities, University of Cape Town, South Africa

V Musiime, Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda; Joint Clinical Research Centre, Kampala, Uganda

A R Yakubovich, Department of Social Policy and Intervention, University of Oxford, UK

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Adolescents; HIV/AIDS; Antiretroviral therapy; Symptoms; Side-effects; Adherence; South Africa

Cite this article

South African Medical Journal 2017;107(11):965-975. DOI:10.7196/SAMJ.2017.v107i11.12405

Article History

Date submitted: 2017-10-31
Date published: 2017-10-31

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