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Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease.

Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Kasonde P, Mwiya M, Tsai WY, Thea DM, Zambia Exclusive Breastfeeding Study (ZEB - PLoS ONE (2009)

Bottom Line: We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.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.

View Article: PubMed Central - PubMed

Affiliation: Gertrude H Sergievsky Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. lk24@columbia.edu

ABSTRACT

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.

Conclusion: 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.

Trial registration: (ClinicalTrials.gov) NCT00310726.

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Related in: MedlinePlus

Panel A: HIV-free survival among 229 children in the intervention group whose mothers had less severe disease and would not have been eligible for antiretroviral therapy during pregnancy stratified by whether they adhered to the intervention (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.035).Panel B: HIV-free survival among 97 children in the intervention group whose mothers had advanced disease and would have been eligible for antiretroviral therapy during pregnancy but did not receive it stratified by whether they adhered (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.006).
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pone-0006059-g001: Panel A: HIV-free survival among 229 children in the intervention group whose mothers had less severe disease and would not have been eligible for antiretroviral therapy during pregnancy stratified by whether they adhered to the intervention (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.035).Panel B: HIV-free survival among 97 children in the intervention group whose mothers had advanced disease and would have been eligible for antiretroviral therapy during pregnancy but did not receive it stratified by whether they adhered (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.006).

Mentions: There was significant effect modification by the severity of maternal disease. Children of women with less severe disease during pregnancy had significantly worse outcomes if their mothers were adherent and weaned early compared to infants whose mothers were non-adherent and continued breastfeeding (RH = 2.40 95% CI: 1.04–5.54). In contrast, children born to women with advanced HIV disease had significantly better outcomes if their mothers were adherent (Figure 1). The interaction was significant (p = 0.001) and early weaning remained associated with a more than 2-fold increase in the risk of HIV infection or death (RH = 2.60 95% CI: 1.06–6.36, p = 0.036) among infants born to mothers with less severe disease even after adjusting for maternal hemoglobin, body mass index, parity, and birth weight. No other factors met criteria for inclusion in final multivariable models.


Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease.

Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Kasonde P, Mwiya M, Tsai WY, Thea DM, Zambia Exclusive Breastfeeding Study (ZEB - PLoS ONE (2009)

Panel A: HIV-free survival among 229 children in the intervention group whose mothers had less severe disease and would not have been eligible for antiretroviral therapy during pregnancy stratified by whether they adhered to the intervention (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.035).Panel B: HIV-free survival among 97 children in the intervention group whose mothers had advanced disease and would have been eligible for antiretroviral therapy during pregnancy but did not receive it stratified by whether they adhered (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.006).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2698120&req=5

pone-0006059-g001: Panel A: HIV-free survival among 229 children in the intervention group whose mothers had less severe disease and would not have been eligible for antiretroviral therapy during pregnancy stratified by whether they adhered to the intervention (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.035).Panel B: HIV-free survival among 97 children in the intervention group whose mothers had advanced disease and would have been eligible for antiretroviral therapy during pregnancy but did not receive it stratified by whether they adhered (weaned by the completion of 4 months) (dashed line) or whether they continued breastfeeding after 4 months (solid line) (p = 0.006).
Mentions: There was significant effect modification by the severity of maternal disease. Children of women with less severe disease during pregnancy had significantly worse outcomes if their mothers were adherent and weaned early compared to infants whose mothers were non-adherent and continued breastfeeding (RH = 2.40 95% CI: 1.04–5.54). In contrast, children born to women with advanced HIV disease had significantly better outcomes if their mothers were adherent (Figure 1). The interaction was significant (p = 0.001) and early weaning remained associated with a more than 2-fold increase in the risk of HIV infection or death (RH = 2.60 95% CI: 1.06–6.36, p = 0.036) among infants born to mothers with less severe disease even after adjusting for maternal hemoglobin, body mass index, parity, and birth weight. No other factors met criteria for inclusion in final multivariable models.

Bottom Line: We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.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.

View Article: PubMed Central - PubMed

Affiliation: Gertrude H Sergievsky Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. lk24@columbia.edu

ABSTRACT

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.

Conclusion: 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.

Trial registration: (ClinicalTrials.gov) NCT00310726.

Show MeSH
Related in: MedlinePlus