Studies look at approaches other than antiretrovirals
Breast-feeding has become critical area of research
Now that short-course AZT regimens could become a reality in developing countries, one critical area where more research is needed is the impact of antiretroviral therapy on breast-feeding in developing countries. At the same time, other alternatives, from vaginal washing to cesarean section, are being studied, health officials note.
"A lot of us think that in a breast-feeding population, a short-course regimen that doesn’t have a postpartum component is likely to have more limited efficacy," says Lynne Mofenson, MD, associate branch chief for clinical research at the Center for Research for Mothers and Children at the National Institute of Child Health and Human Development in Bethesda, MD. "So the question is what can you do instead of, or in addition to, that might interrupt breast feeding transmission, and that is clearly the next critical question in the developing world." (See more on breast-feeding issues in the AIDS International supplement, inserted in this issue.)
The only controlled trial studying breast-feeding vs. formula feeding is being conducted in Nairobi. Enrollment has been completed and most of the babies have been born. However, 24 months of follow-up will be needed to determine whether breast-feeding transmission occurs.
Another breast-feeding study, in Ethiopia, is looking at using short-course AZT plus one week of AZT to the infant, who will be weaned early at three months.
Here are other approaches to preventing perinatal transmission currently being studied:
• HIV Immunoglobulin trial. Similar to the U.S. trial that was stopped, this Uganda study is looking at one infusion to the mother at 38 weeks and one infusion to the baby at birth with HIV antibody-positive plasma from Ugandan donors. It will be compared to mother-child pairs given intravenous saline solution.
• Four studies of Vitamin A supplementation in Africa. At least one study in Africa has shown that low vitamin A levels in the mother were associated with increased risk of transmission to the baby. In other study, mothers are given vitamin A only antepartum; in another the vitamins given are multinutrients. A third study gives mothers vitamin A plus multi-nutrients. Two studies, one in Malawi, the other in Tanzania, have completed enrollment and are in follow-up with babies to determine infection status. Results should be completed later this year.
• Vaginal cleansing. As reported recently in the Lancet, this approach didn’t appear to be effective. However, one tantalizing finding was its potential efficacy in women with prolonged duration of membrane rupture. Although not effective in the overall group, it actually was associated with a decrease in neonatal and maternal morbidity, Mofenson says.
• Suppositories. Two studies are looking at suppositories with different antiviral agents. A Phase I study in Côte d’Ivoire was completed and appears to be well tolerated. Another study in Tanzania is looking at chlorhexidine administered using lavage rather than swabbing.
• Cesarean section. A European trial looking at cesarean vs. vaginal delivery has been slow in enrolling patients and may not be able to answer the question. However, the National Institutes of Health in collaboration with French and Italian researchers are conducting a large meta-analysis of 15 different cohort studies involving over 10,000 mother-infant pairs. The analysis will collect data already gathered from previous studies, but is also going back to patient charts to collect additional information, such as CD4 counts, Mofenson says. Analysis should be available by this summer.
"It won’t answer the question definitively in today’s environment where combination therapy is common, but it will provide some information on whether C-section decreases transmission risk in women not receiving therapy or who are receiving only AZT," she adds.
In a study published in AIDS, Swiss researchers reported this year that 31 HIV-positive women given cesareans in addition to AZT prophylaxis had no transmission of virus to their children, compared to 7% for those who had AZT prophylaxis alone.
1. Kind C, Rudin, C, Siegrist C, et al. Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. AIDS 1998; 12:205-210.