Project Grant R01HD121457

Federal Grant Award Summary

Oregon Health & Science University (OHSU) received a $2.72 million Project Grant from the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865) to investigate the effects of long-acting antiretroviral therapy (LA-ART) on immune development in offspring exposed to maternal human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART). The four-year award, effective June 1, 2026 through May 31, 2030, will support translational research using a rhesus macaque model of simian immunodeficiency virus (SIV) infection to distinguish the immunological impacts of maternal HIV infection versus antiretroviral drug exposure on fetal immune development. The research addresses a critical gap in understanding why HIV-exposed uninfected (HEU) children—approximately 16 million globally as of 2023—experience increased risks of poor growth, infection-related mortality, and respiratory disease despite being HIV-negative.

The project will evaluate a novel LA-ART regimen combining FDA-approved drugs lenacapavir and cabotegravir administered bimonthly via injection to female macaques, with three experimental cohorts: SIV-infected LA-ART treated animals, uninfected LA-ART treated animals, and uninfected untreated controls. Offspring delivered naturally will be monitored through six months of age to assess how maternal SIV/LA-ART exposure versus LA-ART alone affects infant immune maturation and function through analysis of hematopoiesis and immune ontogeny, generating mechanistic insights applicable to clinical outcomes in human HEU populations.