Maternal, Fetal, and Neonatal Outcomes of Additional Dihydroartemisinin-Piperaquine to Trimethoprim-Sulfamethoxazole in Intermittent Preventive Treatment for Malaria in HIV-Positive Pregnancies: A Systematic Review and Meta-Analysis

Purpose: This systematic review evaluates the addition of Dihydroartemisinin-Piperaquine (DHA-PPQ) to Trimethoprim-Sulfamethoxazole (TMP-SMX) for Intermittent Preventive Treatment (IPT) in HIV-positive pregnancies, focusing on its effects on malaria infection, maternal adverse events, fetal adverse events, and birth outcomes. Patients and Methods: Following PRISMA guidelines, we searched PubMed, Cochrane, Google Scholar, and Scopus until December 16, 2024. Out of 390 studies, three were included, assessed for bias using ROB 2.0, and analyzed with random-effects meta-analysis in RevMan 5.4.1. Results: We analyzed three studies involving 1353 participants who received 800/160 mg of TMP-SMX, with or without 40/320 mg of DHA-PPQ administered three times. The addition of DHA-PPQ showed a non-significant trend toward lower malaria infection outcomes, including maternal parasitaemia (OR: 0.83; 95% CI 0.52, 1.33, p = 0.44) and rates of placental malaria (OR: 0.66; 95% CI 0.40, 1.08, p = 0.10). DHA-PPQ significantly lowered maternal adverse events (OR: 0.78; 95% CI 0.67, 0.91, p = 0.003), which included low hemoglobin (OR: 0.83; 95% CI 0.69, 1.00, p = 0.05), gastrointestinal events (OR: 0.66; 95% CI 0.46, 0.95, p = 0.03), neurological events (OR: 0.61; 95% CI 0.22, 1.69, p = 0.35), and skin reactions (OR: 0.40; 95% CI 0.08, 2.11, p = 0.28). No significant differences were observed in fetal adverse events (OR: 1.05; 95% CI 0.68, 1.65, p = 0.69), which comprised spontaneous abortion (OR: 1.81; 95% CI 0.60, 5.51, p = 0.30), stillbirth (OR: 1.02; 95% CI 0.55, 1.89, p = 0.95), and congenital anomalies (OR: 0.89; 95% CI 0.32, 2.47, p = 0.83). Finally, no significant effect was observed on birth outcomes (OR: 1.13; 95% CI 0.88, 1.45, p = 0.81), including low birth weight (OR: 1.15; 95% CI 0.85, 1.56, p = 0.36) and premature birth (OR: 1.08; 95% CI 0.70, 1.68, p = 0.73). Conclusion: Additional DHA-PPQ shows promising efficacy in reducing malaria infection, a statistically significant reduction in maternal adverse events, with no significant differences in fetal and birth outcomes. Keywords: malaria, HIV-positive pregnancies, TMP-SMX, DHA-PPQ