Background
Sub-Saharan Africa bears the highest global burden of HIV/AIDS, with significant benefits from antiretroviral therapy (ART) affected by challenges such as drug resistance, suboptimal dosing, and wide inter-individual variability in drug response.1,2 Endemic co-infections also further complicate ART optimization. Pharmacometric approaches including population pharmacokinetic (popPK) and physiologically-based pharmacokinetic (PBPK) modeling quantify these influences to guide individualized dosing.3 This systematic review evaluates pharmacometric applications in African HIV/AIDS research, highlighting study trends, methodological approaches, and knowledge gaps to inform future research and policy.
Methods
We conducted a systematic literature search from inception till 2025 in PubMed, Google Scholar, and JSTOR databases for studies applying pharmacometric models to HIV/AIDS in Africa. Two reviewers independently screened studies using predefined inclusion/exclusion criteria (excluding non-compartmental analyses). Data on modeling methods, software tools, study populations, co-infections, and ART drugs were extracted and synthesized.
Results
From 478 articles screened, 54 studies met inclusion criteria. Most (94%) used popPK; while (6%) used PBPK models. NONMEM and Monolix were the dominant modeling tools; others included SAS, R, SIMCA, STATA, and Simulx. All studies focused on HIV; one-third (33%) addressed HIV/tuberculosis co-infection, and two studies examined HIV/malaria co-infection. Efavirenz was the most studied ART (41%). Most studies were conducted in South Africa, Uganda, and Zimbabwe, and cohorts were primarily adults, though several included children and pregnant women. The publication trend showed a steady increase from 2008–2015, a marked surge during 2016–2020, and the highest output in 2021–2025, when advanced pharmacometric platforms were most frequently applied.
Conclusion
Pharmacometric modeling optimizes ART dosing in African HIV research, yet significant gaps persist. We recommend pan-African collaborations and capacity-building to integrate advanced modeling techniques and real-world clinical data. Closer partnerships among pharmacometricians, clinicians, and policymakers can translate these insights into locally adapted dosage recommendations and improved clinical outcomes throughout Africa.
References
1. Ngara B, Zvada S, Chawana TD, Stray-Pedersen B, Fungai C, Simbarashe Rusakaniko. A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir: a study of HIV-infected Zimbabwean adolescents. BMC Pharmacology and Toxicology. 2020 Aug 3;21(1).
2. Abdelwahab MT, Wasserman S, James, Dheda K, Wiesner L, Gandhi NR, et al. Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis. Antimicrobial Agents and Chemotherapy. 2021 Sep 20;65(12).
3. Usman M, Khadka S, Saleem M, Rasheed H, Kunwar B, Ali M. Pharmacometrics: A New Era of Pharmacotherapy and Drug Development in Low- and Middle-Income Countries. Advances in Pharmacological and Pharmaceutical Sciences [Internet]. 2023 Mar 7;2023:3081422. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014156/
