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Results of an open-label, nonrandomized pharmacokinetic study found that antimalarial treatment with dihydroartemisinin/piperaquine (DP) in combination with dolutegravir (DTG)-based antiretroviral therapy (ART) was safe and efficacious among women with HIV infection who were pregnant. These findings were published in the Journal of Antimicrobial Chemotherapy.
Between December 2019 and July 2020, researchers conducted a study that enrolled women (N=13) from Malawi, Africa, who were pregnant and living with HIV infection. All patients were initially on efavirenz-based ART and were subsequently switched to DTG-based ART at 16 weeks’ gestation for a total of 4 weeks. Patients also were coadministered DP for 3 days as prophylaxis against malaria infection. Safety, efficacy, and pharmacokinetic parameters were evaluated.
Among women included in the study, treatment with DP was initiated at a median of 28 (range, 24-33) weeks’ gestation, and 4 patients were on isoniazid and pyridoxine as prophylaxis against tuberculosis (TB) infection.
When was administered alone, the overall 24-hour geometric mean (GM) exposure (area under the curve [AUC]0-24) of DTG was 33,555 ng·h/mL, with a maximum concentration (Cmax) of 2504 ng/mL. In addition, the 24-hour trough (C24) of DTG was 495 ng/mL, the time to maximum concentration (Tmax) was 2.3 hours, the time to half-life (t1/2) was 9.0 hours, and the oral clearance (CL/F) was 1.49 L/hour.
Following the coadministration of DTG with DP, the AUC0-24 (GM ratio [GMR], 1.30; 95% CI, 1.11-1.52; P =.004), Cmax (GMR, 1.31; 95% CI, 1.13-1.51; P =.001), and C24 (GMR, 1.42; 95% CI, 1.09-1.85; P =.008) of DTG were significantly increased, and the CL/F (GMR, 0.77; 95% CI, 0.66-0.90; P =.004) was significantly decreased. No differences were observed in regard to the Tmax (GMR, 1.13; 95% CI, 0.80-1.61; P =.379) or t1/2 (GMR, 1.10; 95% CI, 0.95-1.27; P =.063) of DTG.
Similar patterns of exposure were observed among the subset of patients receiving prophylaxis against TB infection.
A total of 16 adverse events (AE) were reported among all 13 patients included in the analysis. With the exception of 1 patient who developed catheter site pain of moderate severity, all AEs were of mild severity. Of note, there were 2 AEs suspected to be associated with DP and DTG coadministration, including nausea and pruritic rash.
All patients maintained HIV virologic suppression (HIV viral load count, <50 copies/mL) throughout the duration of the study.
This study was limited by its small sample size and insufficient power to assess the safety and efficacy of DP coadministered with DTG among the subset of patients receiving prophylaxis against TB infection.
This study found that although the coadministration of DP with DTG-based ART increased exposure to DTG, this combinatorial therapeutic was safe and efficacious among women with HIV infection who were pregnant.
Reference
Banda CG, Nkosi D, Allen E, et al. Effect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV. J Antimicrob Chemother. 2022;dkac081. doi:10.1093/jac/dkac081
