The AIDS epidemic has had a devastating impact on child survival in sub-Saharan Africa. In Botswana, under-five mortality almost doubled from 1990 to 2000. Since then, remarkable progress has been made to prevent pregnant HIV-positive mothers from passing the virus to their infants, either in utero or through breastfeeding. Yet in a study published this July in BMC Pediatrics, Harvard AIDS Initiative (HAI) researchers found that HIV-exposed or infected children in Botswana account for more than half of deaths in children younger than two.
Botswana, a country at the epicenter of the HIV/AIDS epidemic in southern Africa, has a successful national antiretroviral (ART) program to treat those infected with HIV. Particular attention is given to expectant mothers to prevent mother-to-child transmission (PMTCT) of HIV. Currently, about 26% of pregnant women in Botswana are HIV-positive.
At the request of Botswana’s government, researchers conducted a study to determine the current infant mortality rate. “If you don’t know the infant mortality rate, you can’t design interventions to save babies,” said Dr. Roger Shapiro, Principal Investigator of the study.
From January 2012 to March 2013, 3000 mothers (half HIV-infected and half HIV-uninfected) and their 3033 children (1515 HIV-exposed) were enrolled within 48 hours of delivery at five hospital maternity wards in Botswana. Follow up visits were conducted via cell phone at one and three months, then every three months until 24 months after delivery.
By 24 months, 2.1 % of children followed in the study were HIV-infected. Overall, 106 children died for a mortality rate of 3.5 % over two years. Of the 106 children who died, 12 (38 %) were HIV-infected, 70 (4.7 %) were HIV-exposed uninfected (uninfected children of HIV-positive mothers), and 24 (1.6 %) HIV-unexposed.
“Kids who are HIV-exposed are twice as likely to die,” said Dr. Rebecca Zash, the study’s first author and a clinician at Beth Israel Deaconess Medical Center in Boston. “Because so few children are infected and so many are exposed, most of the deaths in Botswana are in that exposed but uninfected group.”
Formula Feeding as a Confounding Factor?
In 1999, attempting to prevent mother-to-child transmission (PMTCT) of HIV, Botswana’s Ministry of Health encouraged HIV-infected mothers to formula feed exclusively and provided them with free formula. At the time, many countries followed a similar policy. This was before ART was freely available in Botswana and before research showed the benefits of breast-feeding for infants born to HIV-infected mothers.
Botswana began to roll out its national ART program in 2001. By 2012, all pregnant HIV-infected women had access to three-drug ART to prevent mother-to-child transmission.
For babies born to mothers with a suppressed viral load on ART, the shift to formula feeding as part of PMTCT efforts may have done more harm than good. Mother’s milk contains immune factors that help protect a newborn from common infectious diseases, even if the mother is infected with HIV. Research at HAI and elsewhere revealed that higher rates of diarrhea and pneumonia are associated with formula feeding.
In the Botswana study, infectious diseases— diarrhea and pneumonia—were the number one cause of death in both HIV-exposed and unexposed kids. HIV-exposed babies were twice as likely to die and almost all of those babies were formula fed. “We suspect that formula feeding contributed to the higher mortality, but because so few HIV-exposed babies were breast fed and so few HIV-unexposed babies were formula fed, we couldn’t disentangle the two,” said Shapiro.
Infant feeding policies in Botswana are slowing changing. New 2016 HIV Clinical Care Guidelines recommend “HIV positive women who are suppressed on ART should be encouraged to breastfeed their children for a maximum of six months.” This makes sense because the fraction of infants who may die from diarrhea and pneumonia as a result of formula feeding is higher than the number who will get HIV-infected under an effective PMTCT program.
The World Health Organization (WHO), which announced new guidelines this July, more strongly endorses breastfeeding. For infants born to HIV-positive mothers who are doing well on ART, the WHO recommends that “mothers living with HIV should breastfeed for at least 12 months and may continue breastfeeding for up to 24 months or longer (similar to the general population) while being fully supported for ART adherence.”
Beyond ART & Breastfeeding
Achieving low child mortality in Botswana will require interventions to decrease maternal HIV prevalence, as well as interventions to improve outcomes among children and adults already affected by HIV.
“Antiretroviral therapy is absolutely needed and making a huge impact, but it’s not the end of the story,” said Zash. “We also have to reduce the number of HIV-infected pregnant women, and that’s going to take time.”
In addition to encouraging breastfeeding and preventing new adult HIV infections, HAI researchers are looking at ways to treat infectious diseases in young children. “One possible measure is increasing the frequency that HIV-exposed kids are seen in pediatric clinics,” said Zash. “Closer monitoring could lead to saved lives.”