Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi. Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women.
Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear.
                In Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women.
                Of HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP.
                In HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted. Intermittent preventive treatment of malaria during pregnancy (IPTp) reduces placental infection, maternal anemia, and low birth weight (LBW). However, the optimal dosing regimen in settings in which human immunodeficiency virus (HIV) is highly prevalent among pregnant women remains controversial.
                We conducted a randomized, double-blind, placebo-controlled study of IPTp comparing the standard 2-dose sulfadoxine-pyrimethamine (SP) regimen with monthly IPTp among a cohort of HIV-positive pregnant Zambian women. Primary outcomes included placental malaria (by smear and histology) and maternal peripheral parasitemia at delivery.
                There were no differences between monthly IPTp (n=224) and standard IPTp (n=232) in placental malaria by histopathology (26% vs. 29%; relative risk [RR], 0.90 [95% confidence interval {CI}, 0.64-1.26]) or placental parasitemia (2% vs. 4%; RR, 0.55 [95% CI, 0.17-1.79]). There also were no differences in maternal anemia, stillbirths, preterm delivery, LBW, or all-cause mortality of infants at 6 weeks.
                In an area of mesoendemicity in Zambia, monthly SP IPTp was not more efficacious than the standard 2-dose regimen for the prevention of placental malaria or adverse birth outcomes. IPTp policy recommendations need to take into account local malaria transmission patterns and the prevalence of HIV.
                ClinicalTrials.gov identifier: NCT00270530.
Three or more doses of SP may have some advantages over the standard two doses in HIV-positive pregnant women, but larger trials would be necessary to confirm an effect on patient important outcomes. However, since SP cannot be administered concurrently with co-trimoxazole - a drug often recommended for infection prophylaxis in HIV-positive pregnant women, new drugs and research is needed to address needs of HIV-positive pregnant women.