Advances and hope for perinatal HIV remission and cure in children and adolescents

Abstract

Purpose of review The known timing of HIV infection in perinatal transmission combined with the capacity for early antiretroviral therapy (ART) initiation and immune reconstitution can provide unique insights into HIV persistence. The scientific basis for a pediatric-specific research agenda aimed at HIV remission and cure is discussed. Recent findings Accumulating evidence supports a favorable biomarker profile for immunotherapeutic interventions in early treated, perinatally-infected individuals. HIV DNA concentrations in infected cells of early treated infants decrease over the first few years of life and, after >10 years of ART, the overwhelming majority of non-induced proviral genomes are replication-deficient. With early ART initiation, approximately half of perinatally-infected individuals become seronegative. Studies of untreated infants and vaccine trials indicate infected infants can generate HIV-specific humoral responses. Taken together, this evidence suggests early treatment results in low levels of replication-competent provirus, an absence of HIV-specific immunity, and the capacity to generate immune responses to potential immunotherapeutic interventions. Summary Perinatally HIV-infected individuals require lifelong ART due to the prompt establishment of viral latency in long-lived resting memory CD4+ T cells that rekindle viremia upon treatment cessation. However, intense research efforts are ongoing to perturb HIV latency towards reservoir clearance for virologic remission and cure in which perinatally-infected individuals can discontinue ART.

Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study (Preprint)

“…In 2015, among youth ages [13][14][15][16][17][18][19][20][21][22][23][24] diagnosed in the United States, 81% were gay and bisexual males. Out of newly diagnosed male youth, 55% were black and 24% were Latino [33].…”

“…Therefore, it has been suggested that adolescents may be more responsive to early cART than adults with better chances of obtaining drug free remission [24]. By identifying this population early and promptly initiating potent ART, with adequate surveillance and dedicated behavioral strategies to retain them in care and optimize ART adherence, it may be possible to significantly limit the size of their latent viral reservoirs and preserve their immune systems.…”

“…When ART is discontinued, these HIV latent reservoirs allow for viral rebound to occur [25] [26]. However, if cART is initiated during the acute phase of infection , it is possible to preserve the CD4 T cells and decrease the size of HIV reservoirs [24] [27] [19]. A period of drug free remission may then be possible [21].…”

“…These reservoirs usually reach a set point within the first two months of infection and serve as predictors of long term HIV control [10] [24]. When ART is discontinued, these HIV latent reservoirs allow for viral rebound to occur [25] [26].…”

Prevention of Mother-to-Child Transmission of HIV in Delta State of Nigeria: Evaluation of the Early Infant Diagnosis Program

“…There has been expectation that perinatal HIV remission and cure is possible in infants 28 , and few cases are beginning to emerge 29 . In this study, 7% (3/41; Table 2) of the positives that were re-tested at the 18 th month appeared equivocally negative and earmarked for further retesting.…”