Denoeud‐Ndam 2014b BEN.

Methods	Trial design: randomized, open‐label trial of 3 doses of IPTp Follow‐up: 3 scheduled IPTp administrations with at least a 1‐month interval between them. IPTp‐mefloquine administration and provision of cotrimoxazole. Clinical and adherence information, complete blood count, CD4 count, malaria screening, and treatment of malaria. At delivery: blood smears from placenta and umbilical cords and evaluation of newborns. Infant evaluation at 6 weeks, 4 months, and 2 months after weaning Adverse event (AE) monitoring: self‐reporting of all AEs. All adverse events were recorded at each visit. In addition, direct observation of early adverse reactions to mefloquine within 30 minutes after supervised intake was noted and later reactions were collected by phone the same day/evening or on the next day. Medical examination was performed 2 weeks after cotrimoxazole initiation to search for cutaneous reactions. An independent data and safety monitoring board reviewed all SAEs.
Participants	Numbers of participants randomized: 72 (cotrimoxazole), 68 (mefloquine) Inclusion criteria: HIV‐infected pregnant women of all gravidities aged > 18 years, living permanently in the study area, between 16 and 28 weeks of gestation, last dosage of IPTp taken 1 month before enrolment, women requiring antimalarial treatment enrolled at least 2 weeks after completion of treatment Exclusion criteria: history of neuropsychiatric disorder; severe kidney or liver disease; serious adverse reaction to mefloquine, sulfa drugs, or quinine
Interventions	IPTp with mefloquine 15 mg/kg single dose (250 mg tablet, Lariam, Roche) Three doses 1 month apart Cotrimoxazole Daily dose of 800 mg sulfamethoxazole and 160 mg trimethoprim All study participants were given LLITNs and daily supplementation with 100 mg ferrous sulphate and 5 mg folic acid. The first dose was given at ≥ 16 weeks of gestation. All women were observed for 30 minutes following IPTp administration. Women vomiting within the first 30 minutes were given a second full IPTp dose. Asymptomatic women and women with low parasitaemia (< 1000 parasites/µL) in the mefloquine groups were treated by the IPTp‐mefloquine dose. Otherwise, women received artemether‐lumefantrine or oral quinine. Thos with severe malaria were treated with intravenous quinine.
Outcomes	Maternal peripheral parasitaemia at delivery (PCR) Placental parasitaemia at delivery (blood smear and PCR) Mean maternal haemoglobin at delivery Maternal anaemia (< 9.5 g/dL) at delivery Cord blood parasitaemia at delivery Mean birth weight Low birth weight (< 2500 g) Prematurity Serious adverse events (SAEs) during pregnancy Spontaneous abortions (< 28 weeks) Stillbirths (≥ 28 weeks of gestation) Congenital malformations (< 28 weeks of gestation) Early neonatal mortality (< 7 days) Neonatal mortality Infant deaths after 7 days Vomiting Dizziness Headache Fatigue/weakness
Notes	Country: Benin Setting: 5 urban hospitals with PMTCT programmes Malaria transmission: intense and perennial transmission, with peaks during rainy seasons Resistance: increasing risk of resistance to sulfa drugs. Parasite resistance to cotrimoxazole Dates: 2009 to 2012 Funding: Sidaction Grant AI19‐3‐01528
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Randomization was stratified according to the study site and the number of previous pregnancies".
Allocation concealment (selection bias)	Low risk	Quote: "The study coordination center retained the master list and assigned treatment by phone".
Blinding of participants and personnel (performance bias) All outcomes	High risk	The trial blinded only the microscopist who evaluated blood smears.
Blinding of outcome assessment (detection bias) Efficacy	Low risk	No blinding of outcome assessment was reported, but the review authors judge that the efficacy outcome measurement is not likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Safety	High risk	No blinding of outcome assessment was reported; thus the review authors judge that the safety outcome measurement is likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data were balanced in numbers across groups.
Selective reporting (reporting bias)	Low risk	Protocol was not available, but published report describes all expected outcomes including those prespecified.
Other bias	Low risk	The study appears to be free of other sources of bias.