Malaria in Pregnancy, HIV Infections
Conditions
Keywords
malaria, pregnancy, HIV, prevention, cotrimoxazole, mefloquine
Brief summary
The purpose of this study is to evaluate the efficacy of cotrimoxazole prophylaxis in prevention of malaria during pregnancy in HIV-infected women, compared to intermittent preventive treatment with mefloquine.
Detailed description
Malaria infection during pregnancy can have adverse effects on both mother and fetus, including maternal anaemia and low birth weight which are responsible for mother and infant mortality. It is a particular problem for women in their first and second pregnancies and for women who are HIV-positive. Maternal HIV infection potentiates many of these adverse effects. In HIV-infected women, the World Health Organization (WHO) advocates the use of insecticide-treated bednets, and drugs : If the CD4 cell count is below 350/mm3 or the HIV disease is in WHO stage 2, 3 or 4, cotrimoxazole prophylaxis for the prevention of pneumocystosis and toxoplasmosis is indicated, that is assumed to also protect those women from malaria. Otherwise, they have to receive at least three doses of intermittent preventive treatment (IPT), most commonly with sulfadoxine-pyrimethamine (SP) given at the antenatal care visits. If IPT with SP has been a subject of many investigations, cotrimoxazole efficacy has never been assessed in prevention of malaria during pregnancy. The investigators aim to evaluate the efficacy of cotrimoxazole prophylaxis in prevention of malaria during pregnancy in HIV-infected women. The investigators postulate that cotrimoxazole prophylaxis is not inferior to IPT in all women, unrelated to their CD4 cell count. In the control arm, the investigators will use mefloquine as IPT. The safety and efficacy of this drug have already been assessed in HIV-negative patients (NCT00274235). A randomized controlled trial will be conducted in five hospitals in Benin. Pregnant women will be enrolled both in the Antenatal Care unit and in the Infectious Diseases unit of each setting. All women will receive insecticide-treated bednets at enrolment. Randomization will be stratified by hospital and CD4 cell count range. Women assigned to cotrimoxazole will receive cotrimoxazole prophylaxis daily during all the course of pregnancy. Women assigned to mefloquine IPT will receive mefloquine three times during pregnancy. Women randomised in this arm and having a low CD4 cell count or an advanced HIV disease will also receive cotrimoxazole prophylaxis in prevention of HIV/AIDS opportunistic infections. Drug efficacy will be judged on the prevalence of placental malaria at delivery. This study will contribute to updating the recommendations concerning the prevention of malaria during pregnancy in HIV-infected women.
Interventions
DRUGcotrimoxazole
800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery
DRUGmefloquine
mefloquine 15 mg/Kg three times, between 16 and 28 weeks, 24 and 32 weeks, then 28 and 36 weeks of pregnancy
Sponsors
Sidaction
Saint Antoine University Hospital
National University Hospital, Cotonou
Université d'Abomey-Calavi
Ministry of Health, Benin
Institut de Recherche pour le Developpement
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed HIV seropositivity * Permanent residency in the study catchment's area * Confirmed pregnancy, gestational age\< 28 weeks * More than 18 years of age * Karnofsky index ≥80 * Willingness to deliver at the hospital * Written informed consent
Exclusion criteria
* History of allergy to study drugs : sulpha drugs, mefloquine, quinine * History or presence of major illnesses : severe renal disease , severe hepatic disease, severe neuropsychiatric disease * Mefloquine or halofantrine received within the 4 weeks prior to enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| proportion of placental malaria (presence of parasites in the placental blood smear at delivery) | delivery |
Secondary
| Measure | Time frame |
|---|---|
| proportion of low birth weight infants (<2500 g) and mean birth weight | delivery |
| proportion of maternal anaemia (<11g/dl) and severe maternal anaemia (<8g/dl) at delivery and during pregnancy | course of pregnancy and delivery |
| cord blood malaria infection at delivery (infant parasitemia) | delivery |
| pre-term deliveries (< 37 weeks) | delivery |
| placental malaria mean parasite density at delivery | delivery |
| congenital anomalies | first 6 months of life |
| safety profile of the two treatments: proportion and detailed description of adverse effects in each treatment arm | course of pregnancy (mother) anf first 6 months of life (infant) |
| Mother-to-child HIV transmission rate in each treatment arm | 2 months after breastfeeding cessation |
| To document the effect of cotrimoxazole in reducing infections in HIV-infected women, we will measure the incidence of bacterial and parasitic infections (other than malaria) during pregnancy | course of pregnancy |
| spontaneous abortions (early:<28 weeks, late: ≥28 weeks) and still births | course of pregnancy |
Countries
Benin
Outcome results
None listed