Differential Effects of Early Weaning for HIV-Free Survival of Children Born to HIV-Infected Mothers by Severity of Maternal Disease

Gertrude H Sergievsky Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
PLoS ONE (Impact Factor: 3.23). 02/2009; 4(6):e6059. DOI: 10.1371/journal.pone.0006059
Source: PubMed


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.
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.
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.
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.
( NCT00310726.

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    • "abrupt cessation at 4 mo vs EBF ≥6 mo be used for preventing mother-to-child HIV transmission? Settings: Zambia Bibliography: Kuhn 2005, Kuhn 2008, Arpadi 2009, Kuhn 2009, Fawzy 2011 (ZEBS) "
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    ABSTRACT: In 2012, we conducted systematic reviews for the World Health Organization (WHO) on numerous topics relevant to antiretroviral medicines, treatment as prevention, the continuum of care, prevention of mother-to-child HIV transmission, service delivery and operational questions and other topics. We used standard Cochrane Collaboration methods in conducting the reviews. We used the GRADE methodology to assess evidence quality. Our work informed WHO's 2013 "Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection." This document presents our review on optimal duration of breastfeeding for mothers with HIV infection, breastfeeding their infants, when mothers or infants are receiving antiretroviral medications. Please be aware that this review only includes studies identified up to December 2012. There may have been new studies with relevant data published since that time.
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    • "Our study showed a 40% reduction in likelihood of death or HIV infection by nine to 24 months when mothers initiated HAART for PMTCT, consistent with previous reports of increased HIV-free child survival with use of maternal HAART initiated during pregnancy and extended during breastfeeding [19,33,34]. Breastfeeding with early cessation was reported by 33% of HIV-positive mothers; however, mode of breastfeeding was not associated with HIV-free survival in our study, although previous randomized trials have provided evidence of the negative impact of early and abrupt cessation of breastfeeding on HIV-free survival of children [35,36]. The Rwandan Ministry of Health has already set new national standards and guidelines for PMTCT in line with the 2010 WHO guidelines [11], choosing the option B regimen (every HIV-positive pregnant woman will receive HAART as a lifelong treatment if eligible or as prophylaxis until one week after cessation of breastfeeding) [37]. "
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    ABSTRACT: Operational effectiveness of large-scale national programmes for the prevention of mother to child transmission (PMTCT) of HIV in sub-Saharan Africa remains limited. We report on HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the national PMTCT programme in Rwanda. We conducted a national representative household survey between February and May 2009. Participants were mothers who had attended antenatal care at least once during their most recent pregnancy, and whose children were aged nine to 24 months. A two-stage stratified (geographic location of PMTCT site, maternal HIV status during pregnancy) cluster sampling was used to select mother-infant pairs to be interviewed during household visits. Alive children born from HIV-positive mothers (HIV-exposed children) were tested for HIV according to routine HIV testing protocol. We calculated HIV-free survival at nine to 24 months. We subsequently determined factors associated with mother to child transmission of HIV, child death and HIV-free survival using logistic regression. Out of 1448 HIV-exposed children surveyed, 44 (3.0%) were reported dead by nine months of age. Of the 1340 children alive, 53 (4.0%) tested HIV positive. HIV-free survival was estimated at 91.9% (95% confidence interval: 90.4-93.3%) at nine to 24 months. Adjusting for maternal, child and health system factors, being a member of an association of people living with HIV (adjusted odds ratio: 0.7, 95% CI: 0.1-0.995) improved by 30% HIV-free survival among children, whereas the maternal use of a highly active antiretroviral therapy (HAART) regimen for PMTCT (aOR: 0.6, 95% CI: 0.3-1.07) had a borderline effect. HIV-free survival among HIV-exposed children aged nine to 24 months is estimated at 91.9% in Rwanda. The national PMTCT programme could achieve greater impact on child survival by ensuring access to HAART for all HIV-positive pregnant women in need, improving the quality of the programme in rural areas, and strengthening linkages with community-based support systems, including associations of people living with HIV.
    Journal of the International AIDS Society 01/2012; 15(1):4. DOI:10.1186/1758-2652-15-4 · 5.09 Impact Factor
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    • "HIV-free survival by breastfeeding practice. HIV-free survival of children born to HIV-infected women with CD4 counts >350 is better if breastfeeding continues than if breastfeeding stops early [47]. "
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    ABSTRACT: Clinical and epidemiologic research has identified increasingly effective interventions to reduce mother to child HIV transmission in resource-limited settings These scientific breakthroughs have been implemented in some programmes, although much remains to be done to improve coverage and quality of these programmes. But prevention of HIV transmission is not enough. It is necessary also to consider ways to improve maternal health and protect child survival. A win-win approach is to ensure that all pregnant and lactating women with CD4 counts of <350 cells/mm3 have access to antiretroviral therapy. On its own, this approach will substantially improve maternal health and markedly reduce mother to child HIV transmission during pregnancy and delivery and through breastfeeding. This approach can be combined with additional interventions for women with higher CD4 counts, either extended prophylaxis to infants or extended regimens of antiretroviral drugs to women, to reduce transmission even further. Attempts to encourage women to abstain from all breastfeeding or to shorten the optimal duration of breastfeeding have led to increases in mortality among both uninfected and infected children. A better approach is to support breastfeeding while strengthening programmes to provide antiretroviral therapy for pregnant and lactating women who need it and offering antiretroviral drug interventions through the duration of breastfeeding. This will lead to reduced HIV transmission and will protect the health of women without compromising the health and well-being of infants and young children.
    Journal of the International AIDS Society 12/2009; 12(1):36. DOI:10.1186/1758-2652-12-36 · 5.09 Impact Factor
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