Effectiveness of co-trimoxazole to prevent Plasmodium falciparum malaria in HIV-positive pregnant women in sub-Saharan Africa: an open-label, randomized controlled trial.

BACKGROUND

Human immunodeficiency virus (HIV) and malaria during pregnancy cause substantial perinatal mortality. As co-trimoxazole (CMX) protects children and HIV-positive adults against malaria, we compared the effectiveness of daily CMX with sulfadoxine-pyrimethamine intermittent preventive treatment (IPT-SP) on malaria risk in HIV-positive pregnant women in a Plasmodium falciparum-endemic African area.

METHODS

From January 2009 to April 2011, we included in a randomized noninferiority trial all HIV type 1-infected pregnant women (≤28 weeks' gestation, CD4 count ≥200 cells/µL, hemoglobin level ≥7 g/L) in 19 health centers in Togo. Women were randomly assigned to daily 800 mg/160 mg CMX, or IPT-SP. The primary outcome was the proportion of malaria-free pregnancies. Other outcomes included malaria incidence, parasitemia, placental malaria, anemia, and infants' birth weight.

RESULTS

Of 264 women randomly assigned to the CMX or IPT-SP group, 126 of 132 and 124 of 132, respectively, were included in the analysis. There were 33 confirmed cases of clinical malaria among 31 women in the CMX group, and 19 among 19 women in the IPT-SP group. Ninety-five of 126 (75.4%) women in the CMX group and 105 of 124 (84.7%) in the IPT-SP group remained malaria-free during their pregnancy (difference, 9.3%; 95% confidence interval [CI], -.53 to 19.1, not meeting the predefined noninferiority criterion). The incidence rate in intention-to-treat analysis was 108.8 malaria episodes per 100 person-years in CMX (95% CI, 105.4-112.2) and 90.1 in IPT-SP (95% CI, 86.8-93.4) (not significant). Prevalence of parasitemia was 16.7% in the CMX group vs 28% in the IPT-SP group (P = .02). Histology revealed 20.3% placental malaria in the CMX group vs. 24.6% in the IPT-SP group (not significant). Grade 3-4 anemia was more frequent in the CMX group (10% vs 4%; P = .008). No pregnant women died. Median birth weight was similar.

CONCLUSIONS

Daily CMX was not noninferior to IPT-SP for preventing maternal malaria but safe and at least similar regarding parasitemia or placental malaria and birth outcomes. Clinical Trials Registration  ISRCTN98835811.