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Seeking to Limit HIV Transmission During Breast-Feeding

Drugs work; a policy of early weaning does not.

The use of peripartum antiretroviral prophylaxis to reduce mother-to-child HIV transmission has been one of the biggest triumphs in HIV control. Unfortunately, infants who are protected from intranatal infection can still acquire the virus by breast-feeding, and, after more than a decade of research, few simple solutions are available to address this problem in developing countries. Two large studies now examine different approaches.

In Malawi, investigators conducted a randomized trial of extended prophylaxis among more than 3000 neonates who were born HIV-negative to HIV-positive mothers. All infants received a single dose of nevirapine and 1 week of AZT prophylaxis. Infants in the intervention groups then received a 13-week course of nevirapine, with or without AZT, while those in the control group received no further prophylaxis. About 90% of the mothers breast-fed for at least 6 months; fewer than 5% were receiving antiretrovirals during the 14-week postpartum period.

Between the ages of 6 weeks and 9 months, infants in the intervention groups had significantly lower rates of HIV infection than did those in the control group (protective efficacy >60% at 14 weeks for both extended regimens). From 9 months to 15 months, these differences persisted but were no longer uniformly significant, and, by 24 months, infection rates were similar in all groups. Overall mortality rates were similar across groups; after 6 months, control infants had slightly but not significantly higher mortality rates, apparently because of their higher HIV infection rates. Side effects from the drugs were rare; no information was provided about drug-resistance problems in infants who became infected despite prophylaxis.

A less successful intervention was reported from Zambia, where 958 HIV-infected women were randomized to abruptly wean infants at 4 months or to continue breast-feeding for as long as they liked. Although women in the early-wean group received intensive counseling, formula, and cereal, only 70% successfully weaned their infants by 5 months (vs. 7% in the control group). An intent-to-treat analysis showed only a slight, nonsignificant difference in HIV infection rates between the groups (21% in the early-wean group vs. 26% in controls). Mortality at 24 months was similar for uninfected children in both groups, but, among HIV-infected infants, mortality was significantly higher in the early-wean group.

Comment: These important studies are likely to affect policy — in fact, results from the Zambian study have already weakened the WHO’s previously strong recommendation to stop breast-feeding at 6 months. Still, they raise as many questions as they answer. Antiretrovirals clearly reduce transmission, but the issue of drug resistance is still unresolved, and providing antiretrovirals for the duration of breast-feeding poses a clear financial burden. Meanwhile, limiting breast-feeding could be nutritionally dangerous to sick children and unacceptable to their mothers. Editorialists point out that in this arena, scientists will have to adapt their prevention strategies to a variety of cultural, economic, and psychological factors.

— Abigail Zuger, MD

Published in Journal Watch HIV/AIDS Clinical Care June 4, 2008

Citation(s):

Kumwenda NI et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med 2008 Jun 4; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa0801941)

Kuhn L et al. Effects of early, abrupt weaning for HIV-free survival of children in Zambia. N Engl J Med 2008 Jun 4; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa073788)

Gray GE and Saloojee H. Breast-feeding, antiretroviral prophylaxis, and HIV. N Engl J Med 2008 Jun 4; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMe0803991)

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