Original Research

Effect of obesity on dolutegravir exposure in Black Southern African adults living with HIV

Enkosi Mondleki, Clifford G. Banda, Nomathemba C. Chandiwana, Simiso Sokhela, Lubbe Wiesner, Francois Venter, Gary Maartens, Phumla Z. Sinxadi
Southern African Journal of HIV Medicine | Vol 23, No 1 | a1452 | DOI: https://doi.org/10.4102/sajhivmed.v23i1.1452 | © 2022 Enkosi Mondleki, Clifford G. Banda, Nomathemba C. Chandiwana, Simiso Sokhela, Lubbe Wiesner, Francois Venter, Gary Maartens, Phumla Z. Sinxadi | This work is licensed under CC Attribution 4.0
Submitted: 31 August 2022 | Published: 13 December 2022

About the author(s)

Enkosi Mondleki, Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Clifford G. Banda, Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Nomathemba C. Chandiwana, Ezintsha, University of the Witwatersrand, Johannesburg, South Africa
Simiso Sokhela, Ezintsha, University of the Witwatersrand, Johannesburg, South Africa
Lubbe Wiesner, Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Francois Venter, Ezintsha, University of the Witwatersrand, Johannesburg, South Africa
Gary Maartens, Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
Phumla Z. Sinxadi, Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa


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Abstract

Background: Dolutegravir, a component of the preferred first-line antiretroviral therapy regimen, has been associated with increased weight gain. South Africa has a high prevalence of obesity, especially among women. Understanding dolutegravir exposure in patients with obesity is important for dose optimisation.

Objectives: We compared the pharmacokinetic parameters of dolutegravir in Southern African adults living with HIV with and without obesity.

Method: Blood samples were collected at various time points over a 24 h-period for dolutegravir assays. Non-compartmental analysis was conducted and geometric mean ratios (GMRs), with 90% confidence intervals (CIs), were generated to compare dolutegravir pharmacokinetic parameters between the groups. Regression analyses to assess predictors of dolutegravir exposure were done.

Results: Forty participants were enrolled, 26 were women and 10 had obesity. Dolutegravir area under the concentration-time curve to 24-h and the maximum concentrations were not statistically significantly lower in participants with obesity: GMR 0.91 (90% CI: 0.71–1.16) and GMR 0.86 (90% CI: 0.68–1.07), respectively. In a multivariate linear regression analysis adjusting for age, gender, body mass index, creatinine clearance and randomisation arm (tenofovir alafenamide or tenofovir disoproxil fumarate), a unit increase in body mass index was associated with 1.2% lower dolutegravir area under the concentration-time curve to 24-h (P = 0.035).

Conclusion: Dolutegravir exposure was marginally lower in participants with obesity, but this is not clinically significant. Our findings suggest that there is no need to dose adjust dolutegravir in people with obesity.


Keywords

pharmacokinetics; dolutegravir; obesity; South Africa; antiretroviral treatment optimisation; HIV

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