A model-based comparative meta-analysis of the efficacy of dolutegravir-based and efavirenz-based regimens in HIV-infected patients

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2019-09, Vol.25 (9), p.687-694
• Main Authors: Ota, Ryosaku, Ishii, Hiromu, Tsuda, Masahiro, Higuchi, Yuriko, Yamashita, Fumiyoshi
• Format: Article
• Language: English
• Subjects: Adult; Alkynes; Anti-Retroviral Agents - therapeutic use; Antiretroviral Therapy, Highly Active - methods; Benzoxazines - therapeutic use; Combination antiretroviral therapy; Cyclopropanes; Dolutegravir; Efavirenz; Heterocyclic Compounds, 3-Ring - therapeutic use; HIV Infections - drug therapy; Humans; Model-based meta-analysis; Models, Theoretical; Nonlinear mixed effect modeling; Oxazines; Piperazines; Pyridones
• ISSN: 1341-321X; 1437-7780; 1437-7780
• DOI: 10.1016/j.jiac.2019.03.015

Currently, combinations of typical types of antiretroviral agents have been adopted as chemotherapy for human immunodeficiency virus (HIV) infection, comprising two nucleoside analogue reverse transcriptase inhibitors plus one of a non-nucleoside reverse transcriptase inhibitor, an integrase strand-transfer inhibitor, and a protease inhibitor. Although several meta-analyses have been conducted to determine first-line combination antiretroviral therapy, this has yet to be confirmed due to the technical limitation associated. In the present study, we applied a model-based meta-analysis (MBMA) approach, because it allows integration of information from clinical trials with varying dosing, duration, and sampling time points, resulting in enlargement of available data sources. We performed a bibliographic search to identify clinical trials involving dolutegravir (DTG)-based and efavirenz (EFV)-based regimens in HIV-infected, antiretroviral therapy-naïve adults, and then identified 30 independent trial data. The time course of drug effect was described by a consecutive first-order kinetic model and analyzed using the nonlinear mixed effect modeling approach. The developed model suggests that the DTG-based regimen provides a faster-acting and more sustainable drug effect than the EFV-based regimen. Moreover, the drug effect tends to appear more slowly and decay faster in severe patients having higher viral load or smaller baseline CD4 count.