Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease.
BACKGROUND
We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.


METHODS
958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention) or to continued breastfeeding (control). Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART) became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.


RESULTS
Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98). Children of women with less severe disease during pregnancy (not eligible for ART) had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06-6.36) compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it) who weaned early had better outcomes (p-value interaction = 0.002). In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65-9.39) increase in HIV infection or death among infants of mothers with less severe disease.


CONCLUSIONS
Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding.


BACKGROUND
(ClinicalTrials.gov) NCT00310726.
Kuhn
Louise
L
Gertrude H Sergievsky Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. lk24@columbia.edu
Aldrovandi
Grace M
GM
Sinkala
Moses
M
Kankasa
Chipepo
C
Semrau
Katherine
K
Kasonde
Prisca
P
Mwiya
Mwiya
M
Tsai
Wei-Yann
WY
Thea
Donald M
DM
D015492:AIDS Serodiagnosis; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009035:Mothers; D010349:Patient Compliance; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D016896:Treatment Outcome; D014886:Weaning; D015024:Zambia
D019380:Anti-HIV Agents