Infants exposed to their mother’s antiretroviral treatment (ART) pre- and post-partum do not experience any significant poorer neurocognitive development compared to HIV-negative infants who are never exposed to HIV treatment, reassures a new study.
Triple ART and infant nevirapine prophylaxis are already known to be safe and effective at eliminating HIV transmission during breastfeeding, resulting in minimal adverse effects and high infant survival rates. However, the impact of ART on neurodevelopment outcomes throughout infancy and early childhood are less well known.
HIV-exposed and uninfected infants were identified from the IMPAACT Promoting Maternal and Infant Survival Everywhere (PROMISE), a breastfeeding study assessing several ART regimes for prevention of mother-to-child transmission (PMTCT). Mothers were either randomly assigned triple antiretroviral prophylaxis (lopinavir–ritonavir plus either lamivudine and zidovudine or emtricitabine and tenofovir), or zidovudine alone. After birth, mother and child were randomly assigned to either maternal triple antiretrovirals or infant nevirapine during breastfeeding.
Between August 2013 and December 2014, 861 children were enrolled in this prospective cohort to compare the neurodevelopment of those who had been exposed and those who had not been exposed to HIV treatment. HIV-exposed uninfected children made up 47% of the cohort, while the remaining 53% were HIV unexposed; 48% were enrolled in Malawi, while 52% were enrolled in Kenya. The children were paired based on age, sex, weight, socio-economic background and were followed for up to 60 months.
Neurocognitive development was assessed at 12, 24 and 48 months using the Mullen Scales of Early Learning (MSEL), a comprehensive test assessing visual reception, motor skills, receptive language, and expressive language. At 48 months and 60 months, the Kaufman Assessment Battery for Children, second edition (KABC-II) assessed memory, problem solving, non-verbal communications and simultaneous activities.
No difference was found between the two groups at 12 and 24 months using the MSEL test. At 48 months, however, MSEL cognitive scores were worse for infants whose mothers were not on triple therapy compared to infants whose mothers had stayed on triple therapy both pre- and post-partem.
The KABC-II composite scores (mental processing index) did not differ at 48 or 60 months according to exposure. Importantly, there was no difference in neurocapacity between infants whose mothers were on triple therapy versus infants who were not exposed to ART. The investigators speculate that the improved health of the mother through potent triple-therapy may have resulted in neurodevelopmental benefits for their HIV-exposed and uninfected children. They call for further research in this area, which would include collection of immunological biomarkers (tracking CD4 counts for example).
These results were published in the Lancet HIV and are important in the context of prevention of mother-to-child transmission (PMTCT) programmes in low-resourced contexts. While mothers living with HIV in high-income countries are generally advised to formula-feed their children, meaning their infants have minimal exposure to ART, this is not the case in sub-Saharan Africa. Instead, infants here are normally breastfed, to avoid issues around consistent supply of formula feed and clean water.
Exclusive breastfeeding while the mother is on treatment is highly effective at reducing HIV transmission. In some high-income countries, there is a move to support mothers living with HIV to breastfeed should they wish.
The authors note, “This is the first time such neurodevelopmental outcome findings are available for what has become the standard of care across sub-Saharan Africa, and they are reassuring because prevention of mother-to-child transmission programmes using new maternal triple antiretrovirals continue to be widely rolled out in sub-Saharan Africa and globally.”