SWEN 2008.

Methods	Randomized controlled trial
Participants	Pregnant women who presented to antenatal and delivery facilities in Addis Ababa, Ethiopia, Pune, India, and Kampala, Uganda, who were identified as HIV‐infected, were offered the local standard of care for prevention of MTCT of HIV and provided infant feeding counseling, consistent with WHO/UNICEF guidelines. Women were eligible for study enrolment if they indicated an intention to breastfeed their infants and provided informed consent.
Interventions	In Arm 1 (control arm) of the trials, 200 mg nevirapine was provided to women in labor and 2 mg/kg to infants shortly after birth.  In Arm 2 of the trials, this two‐dose nevirapine regimen was provided in addition to infant dosing of 5 mg nevirapine each day starting at age 7 days through six weeks of life.  The risk of HIV infection and death at 6 weeks and 6 months of age in infants who were HIV‐uninfected at birth was estimated.  The analysis included data for 1887 infants.
Outcomes	At six weeks of age, more children in the single‐dose nevirapine group than the extended‐dose nevirapine group were infected (relative risk:  0.54; 0.34‐0.86; p=0.009).  However, at six months of age, the risk of transmission was similar (relative risk 0.80; 0.58‐1.10; p=0.16).  HIV‐free survival was higher in the extended prophylaxis arm, at both six weeks (p = 0.008) and six months (p = 0.03).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"For all three countries, block randomisation was used with treatment assignments generated by computer at a central data coordinating centre at Johns Hopkins University. The randomisation list was provided to study pharmacists only in each country."
Allocation concealment?	Unclear risk	"Study products were administered by pre‐filled amber oral syringes in Ethiopia and Uganda and by opaque dropper bottles in India, after training of mothers by study pharmacists .A number of specific study procedures were implemented to introduce some degree of masking of study staff and care givers. Specifically, none of the study investigators or staff, with the exception of the study pharmacists and a member of the central data management team, had access to the randomization assignments for study participants." Because study pharmacists knew the randomization assignments, however, and worked directly with the mothers, it is possible that allocation was not sufficiently well concealed.
Blinding? All outcomes	High risk	"This study was not blinded"; However, "[t]he reliability of the HIV PCR results were assessed through a centralised quality assurance programme, coordinated by the laboratory of one of the authors (JBJ) at Johns Hopkins School of Medicine, which included blinded retesting of samples from HIV‐infected infants and a random sample of HIV‐uninfected infants. Final infant infection status was assigned for each country by a blinded study investigator and results from all three countries were subsequently reviewed by a fourth blinded investigator (JBJ) to ensure consistency across the countries.
Incomplete outcome data addressed? All outcomes	Low risk	"Since many infant deaths occurred at home or outside of the study clinics, information about the cause of these deaths was limited to verbal autopsy interviews of mothers and other family members. Thus, HIV status at the time of death was not available for infants who could have become HIV positive between their last study visit and their death. 38 (72%) of the deaths occurred among infants for whom their last HIV screening test was negative by HIV PCR. However, the mean time from this last study visit until death was 13·8 (SD 17·7) days, decreasing the likelihood that we failed to identify HIV‐infected infants before their death. We assessed the distribution of mortality by sex, because of an imbalance between study groups at baseline, but there was no significant difference between males and females in terms of the distribution of overall mortality (data not shown). We found no differences between groups in other factors that might be associated with infant mortality, including maternal age, maternal CD4 cell count, maternal viral load (available in India and Uganda), maternal education level, parity, gravidity, and gestational age at enrolment (data not shown)."
Free of selective reporting?	Low risk	No problems apparent.
Free of other bias?	Low risk	No problems apparent.