Natureeba 2017.

Study characteristics
Methods	Double‐blind, randomized, placebo‐controlled superiority trial
Participants	200 HIV‐positive pregnant women living in Tororo, Uganda Inclusion criteria HIV‐1 infection, confirmed by 2 assays Age ≥ 16 years Living within 30 km of the study site Gestation of 12 to 28 weeks confirmed by ultrasound Exclusion criteria History of any adverse events associated with cotrimoxazole or dihydroartemisinin/piperaquine therapy Active medical problem requiring inpatient evaluation WHO HIV disease stage 4 conditions not stable under treatment History of cardiac problems Signs of labour Current intake of ritonavir, drugs associated with known risk of torsades de pointes, or Cyt P450 3A inhibitors medications
Interventions	Daily cotrimoxazole plus monthly dihydroartemisinin‐piperaquine vs daily cotrimoxazole plus monthly placebo
Outcomes	The primary outcome was prevalence of placental malaria and incidence of malaria. Secondary outcomes included maternal peripheral parasitaemia during pregnancy and at delivery, maternal anaemia, cord blood parasitaemia, adverse birth outcomes, and adverse drug reactionss.
Notes	All participants received an LLIN. All participants received combination ART with efavirenz/tenofovir/lamivudine.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was performed in a 1:1 ratio using permuted variable‐sized blocks of 4 and 6.
Allocation concealment (selection bias)	Low risk	Pharmacists not otherwise involved in the study were responsible for treatment allocation and preparation of study drugs.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The study is a double‐blind, placebo‐controlled RCT. Participants assigned to receive daily CTXp alone were given placebo with the same appearance and number of tablets as active dihydroartemisinin/piperaquine.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Investigators assessing blood smears and placental histopathology were blinded to both treatment assignment and findings of prior assessments. Blinding of other staff involved in outcome assessment is unclear.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The study does not explain why not all (194/200, 97%) of enrolled women had placental tissue collected for histopathologic analysis (4 in the daily CTXp arm and 2 in the daily CTXp + monthly dihydroartemisinin/piperaquine arm).
Selective reporting (reporting bias)	Low risk	Not observed
Other bias	Unclear risk	Possible selection bias due to a difference in baseline characteristics between the groups: a higher proportion of primigravidae enrolled in the CTXp plus monthly dihydroartemisinin/piperaquine arm. It is not clear whether this difference was accounted for during data analysis. Adherence to treatment was not reported.

Abbreviations
ART: antiretroviral therapy; ATP: according to protocol; CD4: white blood cells with CD4 glycoprotein in their surface; CDC: Centers for Disease Control; CTXp: daily cotrimoxazole prophylaxis; HIV: human immunodeficiency virus; IPTp: intermittent preventive treatment of pregnancy; ITT: intention to treat; LLIN: long‐lasting insecticidal net; mg: milligrams; μL: microlitre; PCR: polymerase chain reaction; PMTCT: prevention of mother‐to‐child transmission; RCT: randomized controlled trial; SAE: severe adverse event; SP: sulfadoxine‐pyrimethamine; WHO: World Health Organization; vs: versus