Effectiveness of two antifolate prophylactic strategies against malaria in HIV-positive pregnant women in Bangui, Central African Republic: study protocol for a randomized controlled trial (MACOMBA).

International audienceBACKGROUND: Co-infection with malaria parasite and HIV is an emerging public health problem in tropical areas, particularly in pregnant women, and management of the concurrent effects of these two infections is challenging. Co-trimoxazole is a sulfamide preparation used to prevent opportunistic infections in HIV-infected patients, and many studies have reported that it has significant activity against malaria. As the efficacy of intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) against malaria is decreasing, co-trimoxazole might be an alternative for preventing malaria among HIV-infected populations. The aim of this study is to compare the effectiveness of SP-IPT, which is recommended for the prevention of malaria during pregnancy in the Central African Republic, with that of a daily dose of co-trimoxazole against P. falciparum infections among HIV-infected pregnant women in Bangui, the capital of the Central African Republic. METHODS/DESIGN: The MACOMBA study (MAternity and COntrol of Malaria-HIV co-infection in BAngui) is a multicentre open-label randomized clinical trial conducted at four maternity hospitals in Bangui. All HIV-infected pregnant women presenting for an antenatal clinic visit between the weeks 16 and 28 of amenorrhoea, with a CD4 count of more than 350 cells/mm3, will be eligible. All the women will provide written consent before being enrolled in the study and will then be randomly allocated to either SP-IPT (25 mg of sulfadoxine and 1.25 mg of pyrimethamine) or daily co-trimoxazole doses (960 mg per dose). The primary end-point is the placental malaria parasitaemia rate at delivery. Other main outcome measures include the number of malaria episodes during pregnancy, safety, and treatment compliance. Furthermore, the frequency of molecular resistance markers dhfr and dhps will be measured. DISCUSSION: In this trial, we seek to confirm whether co-trimoxazole is operationally suitable to replace SP-IPT in order to prevent malaria among pregnant women infected with HIV in the Central African Republic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01746199

Cotrimoxazole versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in HIV-infected pregnant women in Bangui, Central African Republic: a Pragmatic Randomized Controlled Trial

OBJECTIVE: The main objective of the MACOMBA (Maternity and Control of Malaria-HIV co-infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than Sulphadoxine-Pyremethamine-IPTp (IPTp-SP) to prevent placental malaria infection (primary endpoint) among HIV-positive pregnant women with a CD4+ count ≥350 cells/mm(3) in Bangui, CAR. METHODS: MACOMBA is a multicenter, open-label randomized trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomized and 112 (59 and 53 in CTX and IPTp-SP arms, respectively) were assessed for placental infection defined by microscopic parasitemia or PCR. RESULTS: Thirteen women had a placental infection: 5 in the CTX arm (1 by microscopic placental parasitemia and 4 by PCR) and 8 by PCR in the SP-IPTp (8.5% vs 15.1%, p = 0.28). The percentage of newborns with low birthweight (< 2500 g) did not differ statistically between the two arms. Self-reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms. CONCLUSION: Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV-infected pregnant women, as currently recommended by WHO