Kumwenda 2008.

Methods	Randomized controlled trial
Participants	Pregnant women who presented for either antenatal or delivery services at specific health centers in Blantyre, Malawi were offered HIV counseling and testing.  All women with HIV infection, except those late presenters whose HIV infection was not identified until after they gave birth, received a single intrapartum dose of nevirapine.  Women could be enrolled in the trial if they had HIV infection, were at least 18 years of age (although women <18 years of age could be enrolled if they consented and a guardian gave permission), were pregnant or had given birth within the previous 24 hours at one of the study clinics, were a resident of the study area, were willing to return for postnatal follow‐up visits for up to 2 years, and intended to breastfeed.  The study excluded infants with life‐threatening conditions requiring immediate care.  Mothers were counseled to breastfeed exclusively for six months and to consider weaning thereafter.
Interventions	Arm 1:  single dose nevirapine PLUS 1 week of zidovudine (control regimen) Arm 2:  control regimen PLUS daily nevirapine starting at age 7 days until the age of 14 weeks Arm 3:  control regimen PLUS daily nevirapine with zidovudine starting at age 7 days until the age of 14 weeks The control regimen was single dose nevirapine PLUS 1 week of zidovudine. (Those women who enrolled early enough received one dose of intrapartum nevirapine; some women (approximately 30%) presented too late to receive intrapartum nevirapine.)
Outcomes	HIV infection status: Of 3016 infants, 255 were found to have HIV infection (242 confirmed and 13 presumptive). Among infants who were not infected at birth, between the ages of 6 weeks and 18 months, the control group had consistently higher rates of HIV infection, as compared with both extended‐prophylaxis groups.  At 9 months, the estimated rate of HIV infection (primary end point) was 10.6% in the control group, 5.2% extended nevirapine group (P < 0.001), 6.4% in extended dual prophylaxis group (P = 0.002).  There were no significant differences between the two extended‐prophylaxis groups.  The estimated protective efficacy of the extended prophylaxis regimens were: 6 weeks:    Nevirapine:  67% (95%CI: 43‐81) Nevirapine + Zidovudine:  69% (95%CI: 45‐83) 14 weeks:  Nevirapine:  67% (95%CI: 49‐79) Nevirapine + Zidovudine:  66% (95%CI: 48‐78) 6 months:  Nevirapine:   60% (95%CI: 42‐73) Nevirapine + Zidovudine:  49% (95%CI: 27‐64) 9 months:  Nevirapine:   51% (95%CI: 30‐66)        Nevirapine + Zidovudine:  40% (95%CI: 16‐57) Mortality: No statistically significant differences in mortality by study arm. HIV‐free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group.
Notes	Adverse effects: Infants receiving nevirapine + zidovudine prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) deemed possibly related to a study drug.  There was no difference in adverse events between the control group and the nevirapine only prophylaxis group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"Randomization procedures employed permutated block algorithms of sizes 9 and 12, stratified by study clinic. A computer generated randomization list assigned infants to the appropriate treatment arms using a 1:1:1 allocation ratio. Randomization numbers were placed in sequentially labeled and sealed envelopes." (From Kumwenda 2008)
Allocation concealment?	High risk	Not addressed
Blinding? All outcomes	High risk	This study was not blinded.
Incomplete outcome data addressed? All outcomes	Low risk	"All Grade 3‐4 toxicities, rashes Grade 2B or higher and ALT levels Grade 2 or higher were considered serious. Serious adverse events, including deaths and hospitalizations, were reported to the University of Malawi, Johns Hopkins University, and CDC Institutional Review Boards (IRBs). Abnormal clinical and laboratory findings were followed until resolution to Grade 2 or lower. Infants discontinued from study drug(s) were followed for the study duration." (From Kumwenda 2008 Supplement)
Free of selective reporting?	Low risk	No problems apparent
Free of other bias?	Low risk	No problems apparent.