Boston, MA -- HIV infection among infants remains an enormous global health challenge. Each day, 300 to 500 infants in sub-Saharan Africa become infected with the virus. HIV progresses much faster in infants than in adults because of their weaker immune systems. While antiretroviral drugs are highly effective at suppressing HIV in newborns and infants, these drugs are typically not administered immediately after birth, at least not in most countries hardest hit by the HIV epidemic. In 2010, an infant with HIV born in Mississippi was given antiretroviral therapy (ART) within 30 hours of her birth. This infant was then able to maintain spontaneous viral control for several months after stopping antiretroviral therapy, raising the possibility that early treatment might make a critical difference for newborns. The Early Infant Treatment (EIT) Study, led by Roger Shapiro, MD, MPH, from the Harvard T.H. Chan School of Public Health and Mathias Lichterfeld, MD, PhD, and Daniel Kuritzkes, MD, both from Brigham and Women's Hospital, sought to further investigate this possibility in newborns from Botswana. As part of an international collaborative effort, investigators from the Brigham conducted immunological and virological testing, finding that initiating ART immediately, rather than waiting a few weeks, provided measurable benefits for infants born with HIV. The team's results are published in Science Translational Medicine.
"Our study suggests that strategies to test and treat infants immediately after birth may improve outcomes. We find that ART initiation within hours after birth is doable and translates into multiple benefits for the infants -- lower frequencies of reservoir cells and improved immune responses," said Lichterfeld, the corresponding author and an associate physician in the Division of Infectious Diseases at the Brigham. Lichterfeld is also an associate member of the Ragon Institute of MGH, MIT and Harvard; and an associate nember of the Broad Institute of MIT and Harvard. "What excites me most about this work is that making a comparatively small change in the timing of treatment may have a large impact on long-term treatment outcomes."
The EIT study is a prospective clinical trial that enrolled infants from two major maternity hospitals in the Francistown and Gaborone regions of Botswana, a country with the third highest HIV-1 prevalence in the world. Infants enrolled in the study began ART in the first days (frequently, within hours) immediately following their births. The team compared their results to those of infants not in the study who received ART later (within a median of four months after birth). Infants were then followed for two years with blood sampling at regular intervals.
Investigators focused on 10 infants enrolled in the EIT study who were HIV positive at birth. They measured the number of virally infected cells (typically called viral reservoir cells) and many different types of innate and adaptive immune responses. The team observed that the number of reservoir cells was extremely small (significantly smaller than in adults who were on ART for a median of 16 years). The number of reservoir cells was also significantly smaller than in infected infants who started treatment later. The team also identified specific types of innate immune cells (NK cells and monocytes) that were on the rise while the viral reservoir size shrank, suggesting that these cells may influence or modulate viral reservoir cells.
The authors note that the current study is quite small, entailing the analysis of just 10 EIT infants. A total of 40 infants have been recruited into the study, and samples from the remaining infants are now being analyzed. In addition, a new clinical trial has been started with some of the EIT infants in which a different treatment (broadly-neutralizing antibodies) is being evaluated.
This project was supported by the National Institutes of Health (U01 AI114235, AI120850, AI098487, AI106468, AI117841, AI120008, AI124776, AI130005, AI122377, AI135940, AI116228, AI078799, HL134539, AI125109, and DA047034. Lichterfeld has received speaking and consulting honoraria from Merck and Gilead. A co-author has received consulting honoraria and/or research support from Gilead, Merck, and ViiV.
Science Translational Medicine