Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth

Abstract

Early antiretroviral therapy (ART) in HIV-infected infants generally fails to achieve a sustained state of ART-free virologic remission, even after years of treatment. Our studies show that viral reservoir seeding is different in neonatal macaques intravenously exposed to SIV at birth, in contrast to adults. Furthermore, one month of ART including an integrase inhibitor, initiated at day 3, but not day 4 or 5 post infection, efficiently and rapidly suppresses viremia to undetectable levels. Intervention initiated at day 3 post infection and continued for 9 months achieves a sustained virologic remission in 4 of 5 infants. Collectively, an early intervention strategy within a key timeframe and regimen may result in viral remission or successful post-exposure prophylaxis for neonatal SIV infection, which may be clinically relevant for optimizing treatment strategies for HIV-infected or exposed infants.

More than the Infinite Monkey Theorem: NHP Models in the Development of a Pediatric HIV Cure

“…The duration of infection prior to ART start, as well as the duration of ART, have been shown to influence viral rebound kinetics in adult rhesus macaques [ 121 – 123 ]. To assess the influence of early ART on viral rebound in the pediatric setting, Wang et al challenged newborn rhesus macaques with SIVmac251 intravenously 6 h after birth, started ART 3-day post-infection, and then stopped ART 9 months later [ 124 ]. Four out of 5 animals had no evidence of viral rebound, and the animal that rebounded was the only one with evidence of integrated SIV DNA in axillary lymph nodes and detectable levels of SIV RNA in the rectum.…”