Peripartum ART does not affect offspring cognition
Use of triple antiretroviral therapy (ART) during pregnancy and breastfeeding did not affect the cognitive development and function of the offspring compared with those whose mothers were not exposed to ART, reveals the IMPAACT PROMISE-BF study presented at the IAC 2018.
“Triple ARTs during pregnancy and breastfeeding dramatically decrease the risk of HIV transmission from mothers to infants,” said Professor Michael Boivin of Michigan State University in East Lansing, Michigan, US. However, there was concern that exposure to triple-ART prophylaxis during antepartum and postpartum period may affect infant neurodevelopment.
To address this concern, the investigators compared the developmental outcomes of the ART-exposed offspring of HIV-infected mothers (HEU) vs age-matched, uninfected reference who were unexposed to ART (HUU) in Uganda and Malawi. [IAC 2018, abstract WEAB0201]
The study comprises two phases of randomization: antepartum (from 14 weeks gestation to term) and post-partum (during breastfeeding duration up to 18 months). During antepartum period, pregnant HIV-infected mothers were randomized to triple ART prophylaxis or zidovudine (ZDV) alone. In the post-partum phase, mother-newborn dyads were randomized to receive either maternal prophylaxis with triple ART or infant prophylaxis of nevirapine (NVP). Among the 942 offspring enrolled, 465 (49 percent) were HUU.
No significant difference was observed in early learning ability, as indicated by the MSEL* composite cognitive score, among the offspring of different treatment arms and including HUU reference group up to 48 months.
There was also no significant difference in mental processing ability among all offspring at 48 months, as measured by KABC-II**.
“Both ante- and postpartum maternal triple-ART exposure did not result in greater developmental or cognitive risk for their HEU children through 48 months of age compared with HUU children. Overall, HUU and HEU children were developmentally comparable,” said Boivin.
“[Nonetheless,] triple maternal ART and unexposed reference children had the highest point estimates, and were better than other exposure group combinations,” he noted, alluding to groups whereby mothers were removed from triple ART in the post-partum phase.
On the other hand, the researchers found that stunting significantly predicted offspring development and cognition, rather than HIV exposure status per se.
The MSEL cognition composite as well as KABC Mental Processing Index and nonverbal index were significantly related to the WHO standardized height-for-age (HAZ) criteria for stunting (p<0.01 for all).
After adjusting for HAZ, breastfeeding was also significantly associated with better MSEL composite cognitive ability scores at 12 months compared with non-breastfed infants (p<0.008) in Uganda but not Malawi (as most infants were breastfed in Malawi and too few non-breastfed infants were available for comparison).
“Maternal triple ART at both the antepartum and postpartum stage presumably results in better clinical management of HIV disease and viral suppression. Caregiving health and vitality outweighs triple ART exposure risk for impoverished children,” said Boivin.
“Better gestational and post-natal care for the mom allows her to provide better quality of caregiving for the child, enhancing development in the first 1000 days,” he continued, adding that supportive health care for mother and child such as treatment for malaria, anaemia, micronutrient support are important and beneficial child neurodevelopment.