- Email: [email protected]
Breastfeeding in HIV-1-positive mothers
CORRESPONDENCE
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human subjects. Geneva: CIOMS-WHO, 1993. Ziegler J, Cooper D, Johnson R, Gold J. Postnatal transmission of AIDS-associated retrovirus from mother to infant. Lancet 1985; 1: 896–98. Van de Perre P, Siminon A, Msellati P, et al. Postnatal transmission of the human immunodeficiency virus type I from mother to infant: a prospective cohort study in Kigali, Rwanda. N Engl J Med 1991; 325: 593–98.
Authors’ reply Sir—Randomisation in our trial was successful in that the two groups did not significantly differ for any enrolment, delivery, or neonatal characteristics.1 We have previously explained that the different HIV-1 infection rates at birth were probably an artefact of our definition of infant HIV-1 infection status rather than a failure of randomisation.1,2 Marian Tompson and colleagues raise the possibility that more contact with formula-feeding women might have resulted in improved health care. We would not judge such an outcome to bias the results, since it would be a component of the intervention, but it does suggest a mechanism for our observation. If true, more extensive contact with breastfeeders might lower their mortality risk. As we state in the discussion, the high non-adherence rate in the formula group would result in an underestimate of the true risk of maternal death associated with breastfeeding. If selfreported adherence in that group was inaccurate and true adherence was even lower, the underestimate would be even greater. Women were classified as exclusively breastfeeding if they reported that 100% of the infant feeds were from breastmilk. The median duration of breastfeeding among nonadherent women in the formula group was 13 months, compared with 17 months in the breastfeeding group. Although loss to follow-up was a limitation, we found no correlation between that and any marker of HIV-1 disease status, including CD4-cell count or plasma viral load, which might have predicted mortality. The only distinctive feature of women lost to follow-up was lower socioeconomic status. Thus, we find no support for the scenarios suggested by Tompson and colleagues. The effect of breastfeeding on health of HIV-1-infected women is an important issue and we encourage further research in this area. Unfortunately, the analysis of observational data by Coutsoudis and colleagues3 had inadequate power to address the issue of maternal death.
1096
Jeffrey Aleem and colleagues question the ethics of doing such a trial. Randomised trials are ethically justifiable only when a state of equipoise exists—ie, it is unknown which treatment will be associated with better outcome. We did not know whether the risk of HIV-1 transmission through breastfeeding would outweigh the risk of mortality through formulaassociated diarrhoea and other infectious diseases. That a short-course antiretroviral regimen (ie, one that could become the standard of care in less-developed countries) could reduce the risk of mother-to-child transmission of HIV-1 was first reported after the last woman in our trial had delivered. Our protocol underwent independent review and approval, including approval for verbal informed consent, by the ethics review committees of the University of Nairobi and the University of Washington. *Ruth Nduati, Barbra A Richardson, Grace John Stewart, Dorothy A Mbori-Ngacha, Joan Kreiss *Department of Pediatrics, University of Nairobi, Nairobi, Kenya; and Departments of Biostatistics, Medicine, and Epidemiology, University of Washington, Seattle, WA, USA 1
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Nduati R, John G, Mbori-Ngacha D, et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000; 283: 1167–74. Nduati R, Mbori-Ngacha D, John G, Richardson B, Kreiss J. Breastfeeding in women with HIV. JAMA 2000; 284: 956–57. Coutsoudis A, Coovadia H, Pillay K, Kuhn L. Are HIV-infected women who breastfeed at increased risk of mortality? AIDS 2001; 15: 653–55.
Sir—A strength of Nduati and colleauges’ study1 was the random assignment of formula or breastfeeding. They correctly present their primary results by intention-totreat. However, there was high nonadherence to assigned feeding methods. The researchers suggest that the high energy demands of breastfeeding in HIV-1-infected mothers might accelerate the progression to related death. If this effect is true, a higher mortality rate should be apparent in women who are exclusive breastfeeders than in those who mix feeding methods or avoid breastfeeding altogether. Potentially useful additional information could be obtained by taking into account the mortality rates according to a measure of milk production, such as the proportion of daily infant feeds given as breastmilk. Further analysis was also called for by Marie-Louise Newell2 in her accompanying commentary.
Nduati and colleagues’ finding of no excess mortality or morbidity in mothers who breastfed their infants compared with those who did not is reassuring, but the numbers of women involved were small and the study had at most 50% power to exclude a threefold increase in mortality in mothers who breastfed. Their results warrant no change in current policies on infant feeding by HIV-1-infected women,3 which are: when replacement feeding is acceptable, feasible, affordable, sustainable, and safe, avoidance of all breastfeeding by HIV-1-infected mothers is recommended, otherwise, exclusive breastfeeding is recommended during the first months of life; to keep to a minimum risk of HIV-1 transmission, breastfeeding should be discontinued as soon as feasible, taking into account local circumstances, the individual woman’s situation and the risks of replacement feeding (including infections other than HIV-1 and malnutrition); HIV-1infected women should have access to information, follow-up clinical care, and support, including family-planning services and nutritional support. Nduati and colleagues’ results emphasise the need for proper support to mothers who are infected with HIV1 and provide a further reason for women to know their HIV-1 infection status. This information particularly applies to pregnant women who should be given access to programmes to prevent mother-to-child transmission of HIV-1 and access to care and support programmes for HIV-1-related disorders. WHO recommends that such programmes should include the prevention and treatment of opportunistic infections, treatment with antiretroviral drugs if possible, and psychosocial and nutritional support. *Tim Farley, Olivier Fontaine, Philippe Gaillard, Isabelle de Zoysa, Connie Osborne Departments of *Reproductive Health and Research, Child and Adolescent Health and Development, and HIV/AIDS (Prevention), WHO, 1211 Geneva 27, Switzerland 1
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3
Nduati R, Richardson BA, John G, et al. Effect of breastfeeding on mortality among HIV-1 infected women: a randomised trial. Lancet 2001; 357: 1651–55. Newell M-L. Does breastfeeding really affect mortality among HIV-1 infected women? Lancet 2001; 357: 1634–35. WHO. New data on the prevention of mother-to-child transmission of HIV and their policy implications: conclusions and recommendations: WHO technical consultation on behalf of the UNFPA/UNICEF/WHO/UNAIDS interagency task team on mother-to-child transmission of HIV, report no. WHO/RHR/01.28. Geneva: WHO, 2001.
THE LANCET • Vol 358 • September 29, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
3
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human subjects. Geneva: CIOMS-WHO, 1993. Ziegler J, Cooper D, Johnson R, Gold J. Postnatal transmission of AIDS-associated retrovirus from mother to infant. Lancet 1985; 1: 896–98. Van de Perre P, Siminon A, Msellati P, et al. Postnatal transmission of the human immunodeficiency virus type I from mother to infant: a prospective cohort study in Kigali, Rwanda. N Engl J Med 1991; 325: 593–98.
Authors’ reply Sir—Randomisation in our trial was successful in that the two groups did not significantly differ for any enrolment, delivery, or neonatal characteristics.1 We have previously explained that the different HIV-1 infection rates at birth were probably an artefact of our definition of infant HIV-1 infection status rather than a failure of randomisation.1,2 Marian Tompson and colleagues raise the possibility that more contact with formula-feeding women might have resulted in improved health care. We would not judge such an outcome to bias the results, since it would be a component of the intervention, but it does suggest a mechanism for our observation. If true, more extensive contact with breastfeeders might lower their mortality risk. As we state in the discussion, the high non-adherence rate in the formula group would result in an underestimate of the true risk of maternal death associated with breastfeeding. If selfreported adherence in that group was inaccurate and true adherence was even lower, the underestimate would be even greater. Women were classified as exclusively breastfeeding if they reported that 100% of the infant feeds were from breastmilk. The median duration of breastfeeding among nonadherent women in the formula group was 13 months, compared with 17 months in the breastfeeding group. Although loss to follow-up was a limitation, we found no correlation between that and any marker of HIV-1 disease status, including CD4-cell count or plasma viral load, which might have predicted mortality. The only distinctive feature of women lost to follow-up was lower socioeconomic status. Thus, we find no support for the scenarios suggested by Tompson and colleagues. The effect of breastfeeding on health of HIV-1-infected women is an important issue and we encourage further research in this area. Unfortunately, the analysis of observational data by Coutsoudis and colleagues3 had inadequate power to address the issue of maternal death.
1096
Jeffrey Aleem and colleagues question the ethics of doing such a trial. Randomised trials are ethically justifiable only when a state of equipoise exists—ie, it is unknown which treatment will be associated with better outcome. We did not know whether the risk of HIV-1 transmission through breastfeeding would outweigh the risk of mortality through formulaassociated diarrhoea and other infectious diseases. That a short-course antiretroviral regimen (ie, one that could become the standard of care in less-developed countries) could reduce the risk of mother-to-child transmission of HIV-1 was first reported after the last woman in our trial had delivered. Our protocol underwent independent review and approval, including approval for verbal informed consent, by the ethics review committees of the University of Nairobi and the University of Washington. *Ruth Nduati, Barbra A Richardson, Grace John Stewart, Dorothy A Mbori-Ngacha, Joan Kreiss *Department of Pediatrics, University of Nairobi, Nairobi, Kenya; and Departments of Biostatistics, Medicine, and Epidemiology, University of Washington, Seattle, WA, USA 1
2
3
Nduati R, John G, Mbori-Ngacha D, et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000; 283: 1167–74. Nduati R, Mbori-Ngacha D, John G, Richardson B, Kreiss J. Breastfeeding in women with HIV. JAMA 2000; 284: 956–57. Coutsoudis A, Coovadia H, Pillay K, Kuhn L. Are HIV-infected women who breastfeed at increased risk of mortality? AIDS 2001; 15: 653–55.
Sir—A strength of Nduati and colleauges’ study1 was the random assignment of formula or breastfeeding. They correctly present their primary results by intention-totreat. However, there was high nonadherence to assigned feeding methods. The researchers suggest that the high energy demands of breastfeeding in HIV-1-infected mothers might accelerate the progression to related death. If this effect is true, a higher mortality rate should be apparent in women who are exclusive breastfeeders than in those who mix feeding methods or avoid breastfeeding altogether. Potentially useful additional information could be obtained by taking into account the mortality rates according to a measure of milk production, such as the proportion of daily infant feeds given as breastmilk. Further analysis was also called for by Marie-Louise Newell2 in her accompanying commentary.
Nduati and colleagues’ finding of no excess mortality or morbidity in mothers who breastfed their infants compared with those who did not is reassuring, but the numbers of women involved were small and the study had at most 50% power to exclude a threefold increase in mortality in mothers who breastfed. Their results warrant no change in current policies on infant feeding by HIV-1-infected women,3 which are: when replacement feeding is acceptable, feasible, affordable, sustainable, and safe, avoidance of all breastfeeding by HIV-1-infected mothers is recommended, otherwise, exclusive breastfeeding is recommended during the first months of life; to keep to a minimum risk of HIV-1 transmission, breastfeeding should be discontinued as soon as feasible, taking into account local circumstances, the individual woman’s situation and the risks of replacement feeding (including infections other than HIV-1 and malnutrition); HIV-1infected women should have access to information, follow-up clinical care, and support, including family-planning services and nutritional support. Nduati and colleagues’ results emphasise the need for proper support to mothers who are infected with HIV1 and provide a further reason for women to know their HIV-1 infection status. This information particularly applies to pregnant women who should be given access to programmes to prevent mother-to-child transmission of HIV-1 and access to care and support programmes for HIV-1-related disorders. WHO recommends that such programmes should include the prevention and treatment of opportunistic infections, treatment with antiretroviral drugs if possible, and psychosocial and nutritional support. *Tim Farley, Olivier Fontaine, Philippe Gaillard, Isabelle de Zoysa, Connie Osborne Departments of *Reproductive Health and Research, Child and Adolescent Health and Development, and HIV/AIDS (Prevention), WHO, 1211 Geneva 27, Switzerland 1
2
3
Nduati R, Richardson BA, John G, et al. Effect of breastfeeding on mortality among HIV-1 infected women: a randomised trial. Lancet 2001; 357: 1651–55. Newell M-L. Does breastfeeding really affect mortality among HIV-1 infected women? Lancet 2001; 357: 1634–35. WHO. New data on the prevention of mother-to-child transmission of HIV and their policy implications: conclusions and recommendations: WHO technical consultation on behalf of the UNFPA/UNICEF/WHO/UNAIDS interagency task team on mother-to-child transmission of HIV, report no. WHO/RHR/01.28. Geneva: WHO, 2001.
THE LANCET • Vol 358 • September 29, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.