Combination antiretroviral treatment (ART) initiated shortly after HIV infection may prevent seeding of a long-lasting reservoir of latently infected cells in some infants. We propose an interventional study in Botswana to screen for HIV infection from birth and provide immediate ART to infected infants. At 24 months from ART initiation, infants without viral reservoir detection will undergo a controlled treatment interrupton with close evaluation for viral rebound. We will enroll 50 HIV+ infants into two parallel early treatment cohorts: 30 infants who test HIV+ within 72 hours of birth and initiate ART at <7 days of life, and 20 infants who test HIV- within 72 hours of birth but HIV+ within 42 days of life and initiate ART by 56 days of life. Primary study aims will evaluate safety and efficacy of early ART; virologic and immunologic outcomes with early ART;and the possibility of functional cure (or the dynamics of viral rebound) after ART interruption. In Botswana, an established research infrastructure allows rapid diagnosis of HIV infection and high rates of treatment adherence and follow-up. In Boston, specialized virologic and immunologic testing is available to study viral reservoirs and the immunologic impact of early treatment. This unique collaboration will allow for a detailed investigation of how cellular HIV reservoirs, immune responses, and mechanisms of viral long-term persistence can be manipulated through early ART initiation.
The recent description of an infant with functional cure of HIV infection after starting antiretroviral therapy (ART) in the first days of life raises the questionof whether early ART can prevent the seeding of a long-lasting reservoir of latently infected cells in some infants. We propose an interventional study in Botswana to replicate these conditions and study the virologic and immunologic outcomes. At 24 months, infants without viral reservoir detection will undergo a controlled treatment interruption to determine if this strategy can lead t functional cure of HIV infection.
|Kuritzkes, Daniel R (2016) Hematopoietic stem cell transplantation for HIV cure. J Clin Invest 126:432-7|