Early suppression of HIV in mothers reduces childhood health risks

“Exposure to maternal HIV infection during pregnancy and while breastfeeding has been associated with poorer health outcomes and higher risk of mortality among children,” shared Dr. Emily Begnel, a Research Scientist in the Department of Global Health at the University of Washington. While this sounds like bleak news for women living with HIV who wish to start a family, research is well underway to address this challenge. Antiretroviral therapy (ART) has become more routine in recent years, and Dr. Begnel, in collaboration with Dr. Dara Lehman—a Research Associate Professor in the Human Biology Division at Fred Hutchinson Cancer Center—and their colleagues, including those from the University of Nairobi, wanted to know if early ART treatment for mothers helps to improve health outcomes for their young children. Fortunately, their study, which was carried out in Nairobi, Kenya, showed children born to mothers receiving ART for HIV prior to or in early pregnancy had similar rates of acute diarrhea, malaria, hospitalization, and mortality and lower rates of acute respiratory tract infections compared to children born to mothers without HIV. These findings published in BMJ Global Health highlight the critical advancement in children’s healthcare with early access to ART for mothers.

“Many biological, socioeconomic, and behavioral factors are associated with this difference” between health outcomes for children who are HIV-exposed and un-exposed, stated Dr. Begnel. “However, existing studies have been biased by rapid changes to how we diagnose, treat, and prevent HIV.” A key change has been early uptake of ART for mothers living with HIV prior to or in early pregnancy in addition to HIV prophylaxis treatment for infants born to mothers living with HIV. In the past, ART was prescribed to mothers during late pregnancy, at the time of birth, or while breastfeeding, and the use of HIV prophylaxis for infants was limited. How then does early suppression of HIV in mothers and preventative HIV therapy in infants change the landscape of childhood health outcomes for children from mothers living with HIV? “Our study addressed this important gap in data,” commented Dr. Begnel. There are numerous benefits of initiating ART early. “Earlier ART initiation helps improve maternal health and immune system function, which in turn reduces children’s exposure to HIV virus, inflammation, and co-infections during pregnancy and breastfeeding. We hypothesized that this would translate into lower risk of common childhood infections (e.g., diarrhea, respiratory tract infections) and more serious health outcomes (e.g., hospitalization, death).”

This cohort study was thoughtfully designed to overcome limitations from earlier studies. Specifically, methods used to enroll cohorts and collect data in earlier studies introduced bias and made it unclear whether HIV exposure itself or confounding characteristics were responsible for the poorer outcomes among children of mothers living with HIV as compared to children who were HIV unexposed, shared Dr. Begnel. There were three main ways that Dr. Begnel and the research team modified their approach:
1) All HIV-exposed and unexposed children were enrolled from the same neighborhood to better control for measured and unmeasured sociodemographic and health characteristic differences between the two groups.
2) All mothers living with HIV who were enrolled in the study received at least 6 months of ART and most received the same regimen at enrollment and during follow-up to minimize differences in how children experienced HIV-exposure both in utero and while breastfeeding. Additionally, all infants born to women living with HIV received HIV prophylaxis after birth.
3) Many study visits were scheduled approximately every 3 months between infant birth and 24 months of age to more accurately capture childhood health outcomes.“With this strong study design, we were able to more accurately assess the risk of HIV exposure on health outcomes,” added Dr. Begnel.

Remarkably, this study revealed no difference in the risk of diarrhea, malaria, hospitalization, or mortality between children born to mothers living with HIV who received ART early—prior to pregnancy or during early pregnancy—as compared to those born to mothers without HIV, supporting “our hypothesis that earlier initiation of modern ART regimens may reduce the risk of adverse health outcomes,” stated Dr. Begnel. One unexpected but positive finding was that the children born to mothers living with HIV had lower rates of respiratory tract infections, including pneumonia, which was the opposite outcome as several earlier studies in which ART was not available, less effective, or initiated later in pregnancy or after birth. This finding is important and highly encouraging, suggesting that early ART for all women living with HIV, good adherence to infant HIV prophylaxis, and exclusive breastfeeding can support the health of children who are HIV-exposed but uninfected, shared Dr. Begnel. Key takeaways from this study include support for initiatives to improve access to ART for all individuals living with HIV and for HIV prophylaxis treatment for infants born to mothers living with HIV. Importantly, these interventions would not only limit infant exposure to HIV but also support breastfeeding, which is associated with lower morbidity and mortality for all children.

While it is unclear if children followed in this study had better health outcomes than previous cohorts due to changes in how they experienced HIV exposure or due to other factors, such as high uptake of exclusive breastfeeding for 6 months, the authors’ findings show improved health outcomes for children born to mothers living with HIV. “We are interested in repeating this analysis in our research partners’ larger cohorts that have more heterogeneity in these characteristics (i.e. characteristics of HIV exposure, such as, timing of maternal ART initiation, ART regimens, and uptake of HIV prophylaxis among the infants) to see if we can disentangle the mechanisms behind this difference,” shared Dr. Begnel. At the conclusion of this study, one remaining question is whether HIV exposure in utero or shortly after birth has lasting effects on the immune response and/or microbiome development of the child. “We continue to follow this cohort—the children are now approximately 6 years old!—and are working on analyses to compare the growth, immune responses to vaccines, bacterial microbiome and virome composition, and neurodevelopment” between HIV exposed and unexposed children. The extension of this study will also reveal whether older children require interventions to maintain good health outcomes like the children unexposed to HIV.

The spotlighted research was funded by the National Institutes of Health and Canadian Institutes of Health.

Begnel ER, Ojee E, Adhiambo J, Mabele E, Wandika B, Ogweno V, Lim ES, Gantt S, Kinuthia J, Lehman DA, Slyker J, Wamalwa D. 2025. The Linda Kizazi study: a comparison of morbidity and mortality from birth to 2 years between children who are HIV-unexposed and HIV-exposed, uninfected in the era of universal antiretroviral therapy. BMJ Glob Health. 10(1):e015841.