• To test the hypothesis that co-trimoxazole prophylaxis is not inferior to SP intermittent preventive treatment in preventing placental malaria. [ Time Frame: Pregnancy ] [ Designated as safety issue: No ]
  

• To evaluate efficacy of CTX prophylaxis in preventing malaria peripheral parasitaemia. [ Time Frame: Pregnancy ] [ Designated as safety issue: No ]
  
• To evaluate efficacy of CTX prophylaxis in preventing perinatal mortality and in improving birth weight [ Time Frame: At birth ] [ Designated as safety issue: Yes ]
  
• To establish the safety of CTX prophylaxis on the offspring by measuring the gestational age at delivery and birth weight. [ Time Frame: At birth ] [ Designated as safety issue: Yes ]
  
• To compare the efficacy profile of CTX prophylaxis to that of SP intermittent preventive treatment. [ Time Frame: Pregnancy ] [ Designated as safety issue: No ]
  
• To compare the safety profile of CTX prophylaxis to that of SP intermittent preventive treatment. [ Time Frame: Pregnancy ] [ Designated as safety issue: Yes ]
  
• Spontaneous abortion [ Time Frame: </=28 weeks gestation ] [ Designated as safety issue: Yes ]
  
• Pre-term delivery [ Time Frame: <37 completed weeks ] [ Designated as safety issue: Yes ]
  
• Neonatal mortality [ Time Frame: Within 28 days after birth ] [ Designated as safety issue: Yes ]
  
• Maternal mortality [ Time Frame: Up to 6 weeks following delivery ] [ Designated as safety issue: Yes ]
  
• Major and minor birth defects [ Time Frame: At birth and up to 6 weeks ] [ Designated as safety issue: Yes ]
  

Malaria is a major contributor of disease burden in Sub-Saharan Africa, with pregnant women and children being the most vulnerable population. P. falciparum infection in pregnancy leads to parasite sequestration in placental vascular space, with increased risks of abortion, stillbirth, prematurity, intrauterine growth retardation, maternal anaemia, low birth weight (LBW), perinatal, neonatal and infant mortality. In low transmission areas, malaria can evolve towards severe disease with high risk of mortality. In endemic areas, it is still associated with maternal anaemia, LBW and stillbirth. For prevention and control of malaria in pregnancy, WHO recommends Intermittent Preventive Treatment (IPT), insecticide treated nets (ITNs) and case management for malaria and anemia. HIV in pregnancy increases the risk of malaria, LBW, post-natal mortality and also anaemia, suggesting a synergistic interaction between HIV and malaria. In pregnant women, HIV-1 infection decreases the efficacy of sulfadoxine-pyrimethamine(SP)IPT, although 2 or more doses in 2nd and 3rd trimesters still reduce peripheral parasitaemia, placental infections and maternal anaemia.

To date, SP is the only treatment with data on efficacy and safety in IPT: WHO recommends at least 2 doses after the first trimester. But there is a documented increase in SP resistance, so cotrimoxazole (CTX) could be an alternative: many studies in Zambia and Uganda demonstrated that it reduces mortality and morbidity in HIV infected individuals, and CTX prophylaxis significantly improves birth outcomes in women with CD4 count <200.

Concurrent administration of SP and CTX has been associated with increased incidence of severe adverse reactions in HIV-infected patient. WHO has promoted CTX as alternative to SP for IPT in immuno-compromised HIV-infected pregnant women.

Unfortunately, there is no information on effectiveness of daily CTX for preventing placental malaria infection, maternal anaemia and LBW. In the past, CTX has been used to treat malaria in children and daily use of CTX by non-pregnant HIV-infected adults has been associated with a 70% reductions of the incidence of clinical malaria.

In this study, we will target both HIV infected and non-infected pregnant women with CD4≥ 200/µL, with the aim to establish the safety and efficacy of daily CTX in preventing malaria infection during pregnancy and its consequences, by assuming that CTX is not inferior to SP in reducing placental parasitaemia: such information is urgently needed to assist to issue guidelines on IPT in pregnant women.