Among babies born to HIV-infected mothers, those who are fed breast milk and given zidovudine for the first six months of life have a risk of dying or contracting HIV similar to infants who are fed formula and given zidovudine for the first month, according to a randomized study in Botswana.1 By the age of seven months, the breast-fed infants had a higher rate of HIV infection (9% vs. 6%), but the formula-fed infants had a higher rate of death (9% vs. 5%). At the age of 18 months, the proportion of infants who had died or contracted HIV was essentially the same (14–15%) in the two groups.
The study was part of a larger trial of interventions to reduce mother-to-child HIV transmission, which tested both a peripartum intervention (a single dose of nevirapine vs. placebo, given to both mothers and infants) and the postpartum intervention (breast-feeding plus zidovudine vs. formula feeding plus zidovudine). Pregnant women visiting antenatal clinics in southern Botswana during 2001–2003 were eligible for the study if they were HIV-positive but in fairly good health, at 33–35 weeks of gestation and aged 18 years or older. All women were given zidovudine from 34 weeks of gestation until delivery. After delivery, mothers in one group were advised to feed their infants only formula, and their infants were given zidovudine for one month; mothers in the other group were advised to exclusively breast-feed their infants for six months and then wean them, and their infants were given zidovudine for those six months. Infants were examined and tested periodically though age 18 months. Their rates of HIV infection, death, and the two combined were estimated by the Kaplan-Meier method.
Analyses were based on 1,179 live first-born infants. Their mothers had a median age of about 27 years; one-fourth had a primary education, and two-thirds had a secondary education. Sixty-one percent of mothers did not have any monthly personal income. The majority obtained their drinking water from a tap in the yard (55%) and had a private latrine for their household (74%). The infants had a median birth weight of 3.1 kg. About 8% weighed less than 2.5 kg at birth, and 5% were born prematurely.
By the age of seven months, infants fed breast milk and given zidovudine had a higher cumulative rate of HIV infection than their counterparts fed formula and given zidovudine (9% vs. 6%). The difference remained significant at 18 months of age (10% vs. 6%). When the peripartum intervention was also considered, the higher rate of HIV infection associated with breast-feeding relative to formula feeding was more pronounced when infants and mothers had been given nevirapine than when they had been given a placebo.
Seven months after birth, infants fed formula and given zidovudine had a higher cumulative rate of death than their counterparts who had been breast-fed and given zidovudine (9% vs 5%). However, the difference was no longer significant at 18 months of age. Diarrhea and pneumonia were the leading causes of death. When the peripartum intervention was also considered, formula feeding was associated with a higher rate of death than breast-feeding when infants and mothers had been given a placebo; in contrast, breast-feeding was associated with a higher rate of death than formula feeding when they had been given nevirapine.
Eighteen months after birth, breast-fed infants given zidovudine and formula-fed infants given zidovudine had essentially the same cumulative rate of death or HIV infection (15% and 14%, respectively). When the peripartum intervention was also considered, breast-feeding was associated with a higher rate of this outcome than formula feeding when infants and mothers had been given nevirapine; in contrast, formula feeding was associated with a higher rate of this outcome than breast-feeding when they had been given a placebo.
In safety analyses, formula-fed infants given zidovudine had higher rates than their breast-fed counterparts given zidovudine of severe or worse signs or symptoms (18% vs. 13%) and hospitalization (20% vs. 16%) by the age of seven months. However, the breast-fed infants had a higher rate of abnormal blood tests overall (25% vs. 15%), as well as a higher rate of abnormal tests leading to discontinuation of the zidovudine (9% vs. 2%).
The study's results, according to the researchers, do not definitively support prolonged use of zidovudine in infants to prevent mother-to-child transmission of HIV by breast-feeding. At the same time, they note, the findings underscore the need to assess local patterns of childhood illnesses, particularly infectious ones, before implementing formula feeding as an alternative strategy. The researchers conclude that "further study is warranted to determine the efficacy and safety of other interventions to prevent mother-to-child transmission related to breastfeeding, such as the use of maternal HAART [highly active antiretroviral therapy] during the breastfeeding period."—S. London
1. Thior I et al., Breastfeeding plus infant zidovudine prophylaxis for 6 months vs. formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study, Journal of the American Medical Association, 2006, 296(7):794–805.