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

Southern African Journal of HIV Medicine

Field Value
Title Effect of obesity on dolutegravir exposure in Black Southern African adults living with HIV
Creator Mondleki, Enkosi Banda, Clifford G. Chandiwana, Nomathemba C. Sokhela, Simiso Wiesner, Lubbe Venter, Francois Maartens, Gary Sinxadi, Phumla Z.
Subject Clinical pharmacology pharmacokinetics; dolutegravir; obesity; South Africa; antiretroviral treatment optimisation; HIV
Description 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.
Publisher AOSIS
Contributor This work was supported in part by the National Research Foundation (NRF) (Grant numbers UID113983 and UID120647 to P.S.), the Wellcome Trust (grant numbers [212265/Z/18/Z], [203135/Z/16/Z] to G.M.), United States Agency of Infectious Diseases (to S.S., N
Date 2022-12-13
Type info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion — —
Format text/html application/epub+zip text/xml application/pdf
Identifier 10.4102/sajhivmed.v23i1.1452
Source Southern African Journal of HIV Medicine; Vol 23, No 1 (2022); 6 pages 2078-6751 1608-9693
Language eng
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https://sajhivmed.org.za/index.php/hivmed/article/view/1452/2983 https://sajhivmed.org.za/index.php/hivmed/article/view/1452/2984 https://sajhivmed.org.za/index.php/hivmed/article/view/1452/2985 https://sajhivmed.org.za/index.php/hivmed/article/view/1452/2986
Coverage Southern Africa — —
Rights Copyright (c) 2022 Enkosi Mondleki, Clifford G. Banda, Nomathemba C. Chandiwana, Simiso Sokhela, Lubbe Wiesner, Francois Venter, Gary Maartens, Phumla Z. Sinxadi https://creativecommons.org/licenses/by/4.0