Kuhn 2008.

Methods	Randomized controlled trial
Participants	HIV‐infected women were recruited from two antenatal clinics in Lusaka, Zambia that offered VCT and the two dose nevirapine prophylaxis regimen (one dose to mother, one dose to infant) prophylaxis.  Pregnant women (less than 38 weeks gestation) were recruited.  Women could volunteer if they intended to breastfeed for any length of time, accepted treatment with nevirapine, and agreed to be randomly assigned to the intervention or control group.  Exclusion criteria were severe pregnancy complications (e.g., pre‐eclampsia), previous cesarean delivery, and HIV‐related conditions requiring hospitalization. Median CD4 count of mothers at baseline was ˜330 cells/mm3.  The maternal plasma viral load (median) was about 36,000‐41,000 copies/mL.  Slightly over a third of the women were eligible for antiretroviral therapy.  The mean age was 26 years.  84‐85% were married.  Over half of mothers had no schooling or only primary school education. 3216 women and 3276 infants were enrolled, and infants underwent randomization at birth;  of 3276 infants assigned an intervention, 3106 were included in the primary analysis;  of these, 2389 reached the HIV infection endpoint OR did not have HIV infection and were under follow‐up or completed follow‐up. Median maternal age was ˜26 years.  ˜2/3 had < grade 8 education;  median CD4 count was ˜400; ˜2/3 presented early (>4 hours before delivery)
Interventions	Early, abrupt weaning Participants were randomly assigned to one of two groups.  The experimental intervention encouraged women to breastfeed exclusively to 4 months and then to stop breastfeeding abruptly, or as rapidly as possible.  Women in the control group were encouraged to breastfeed exclusively to 6 months, gradually introduce complementary foods, and continue to breastfeed for a duration of their own choice (standard practice).
Outcomes	Child mortality rates were similar by 24 months in the two groups:  23.9% in the intervention group and 24.6% in the control group (p = 0.96).  There was no significant difference in HIV‐free survival between the two groups according to the intention‐to‐treat analysis:  at 24 months of age, 68.4% of children in the intervention group and 64.0% in the control group were alive and not infected with HIV (p = 0.13) Among uninfected children who were still being breastfed at 4 months, there was no significant difference between the groups in HIV‐free survival at 24 months:  83.9% of the children in the intervention group survived to 24 months without HIV infection, as compared with 80.7% in the control group (p = 0.27).  Between 4 and 24 months, rates of postnatal HIV transmission were not significantly different (6.2% in the intervention group and 8.8% in the control group, p = 0.19), and mortality among uninfected children was similar in the two groups (0.7% in the intervention group and 11.7% in the control group, p = 0.71).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Use of a computer algorithm with randomized permuted block design within each site
Allocation concealment?	High risk	"Participants were informed of their assignment at the next (usually second‐month) visit to ensure sufficient time for preparation."
Blinding? All outcomes	High risk	This study was not blinded.
Incomplete outcome data addressed? All outcomes	Low risk	"Home‐visit teams tracked the participants who did not return for appointments. Information about children’s deaths was sought from hospital and clinic records and from interviews with caretakers and health care personnel. The circumstances of all deaths were reviewed to identify the causes of death."
Free of selective reporting?	Low risk	No problems apparent
Free of other bias?	Low risk	No problems apparent