Early Treatment with Integrase Inhibitor Achieves a Functional Cure for Pediatric SIV Infection

Abstract Neonatal HIV infection causes rapid disease progression to end-stage of AIDS if untreated. To date, there are no reported cases of a genuine functional cure in Pediatric AIDS ClinicalTrial Group lacking integrase inhibitor regimen, even when initiated early. In this study, three infant rhesus macaques born on the same day were intravenously infected with SIV on the day of birth and received ART containing tenofovir, FTC, and dolutegravir (DTG) initiated 3 days post infection and continued daily for 9 months. The results showed early ART combination effectively suppressed viral replication to undetectable viremia throughout the treatment course. Remarkably, two of three infants showed complete virologic remission and intestinal CD4+ T cell preservation throughout the period of studyafter analytical treatment interruption (ATI), as well as undetectable cell-associated proviral DNA in PBMCs, axillary lymph nodes (LNs), and rectal biopsies. However, viral rebound was observed in one of the three infants at two months post ATI. Notably, very low levels of integrated proviral SIV DNA were detected in the lymph node of this animal under cART. Sustained virologic remission was achieved in the other two infants despite absence of protective MHC alleles or neutralizing antibody responses. These findings suggest that early integrase inhibitor-based ART, initiated before irreversible proviral reservoir seeding, can completely suppress viral replication and effectively block new viral genome integration, providing a proof of concept that HIV functional cure and possibly a cure is possible, at least in a proportion of infants postnatally infected with HIV.