Interventions Needed to Prevent HIV Spread Through Breastfeeding, Even When Antiretrovirals Used, Study Says

Although short-course regimens of the antiretroviral drugs zidovudine and lamivudine are successful at reducing vertical HIV transmission among mother/infant pairs in resource-poor settings, the benefit of such interventions is reduced by later HIV transmission through breastfeeding, a study appearing in tomorrow's issue of the Lancet states. Dr. Joep Lange of the International Antiviral Therapy Evaluation Center at the University of Amsterdam and colleagues conducted a randomized, double-blind, placebo-controlled study, called PETRA, from June 1996 to January 2000 at five sites in South Africa, Uganda and Tanzania. All of the women were at least 18 years of age, showed evidence of HIV-1 infection, were less than 36 weeks pregnant, did not have any other life-threatening diseases, indicated an absence of fetal abnormalities and had the ability to be followed for 18 months postpartum. Participants were randomly assigned to one of four groups: group A received zidovudine and lamivudine beginning at 36 weeks' gestation along with an intrapartum dosing and a week's worth of drug therapy for mother and infant postpartum; group B received the same intrapartum and postpartum therapy minus the prepartum component; group C received only intrapartum dosing of zidovudine and lamivudine; and group D received a placebo. The majority of the women in the study used breastmilk as their primary source of infant feeding after delivery.

Results
HIV transmission rates at six weeks postpartum for infants in each group are listed below:

• Group A: 5.7%
• Group B: 8.9%
• Group C: 14.2%
• Group D: 15.3%

• Group A: 7%
• Group B: 11.6%
• Group C: 17.5%
• Group D: 18.1%

• Group A: 15%
• Group B: 18%
• Group C: 20%
• Group D: 22%

Conclusions
The researchers concluded that although the treatment regimens followed by both the A and B groups were effective at reducing HIV transmission at birth, the benefits of the regimens "diminished considerably" after 18 months because of HIV transmission through breastfeeding. The authors note that "ways must be found to minimize" the risk of HIV transmission through breastfeeding. They recommend investigating whether shortening breastfeeding time to six months and simultaneously administering prophylactic antiretrovirals to nursing mothers and uninfected infants may protect against HIV transmission. However, they acknowledge that in resource-poor settings, such as the regions where the study was conducted, it is "simply not possible [to forgo breastfeeding] for social, hygienic and financial reasons" (Lange et al., Lancet, 4/6).

Treating Women
In an accompanying commentary, Karen Beckerman of the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California-San Francisco writes that "prophylaxis against mother-to-child transmission must be linked to preventing the creation of orphans." She notes that with or without drug intervention, most children born to HIV-positive women will not acquire the virus. However, within two years of giving birth, 11% of HIV-positive breastfeeding mothers die. Beckerman states that although much has been done to reduce vertical HIV transmission, "strategies to prevent the creation of orphans -- that is, saving the lives of parents -- are rarely discussed," despite evidence in Western studies that treating pregnant women for HIV results in "far lower" HIV transmission rates than mother-to-child interventions alone. She notes that the study does not mention maternal-health endpoints and no maternal mortality data is given after six weeks during the follow-up period. "Now, in the third decade of AIDS, HIV prevention and AIDS treatment can and must be integral parts of the global response to the AIDS catastrophe," Beckerman states, concluding, "What better place to start than with mothers and children?" (Beckerman, Lancet, 4/6).