Pediatric HIV: the Potential of Immune Therapeutics to Achieve Viral Remission and Functional Cure

• Type of Material: Article
• Authors: Stella J Berendam, Duke University; Ashley N Nelson, Duke University; Ria Goswami, Duke University; Deborah Persaud, Johns Hopkins University; Nancy L Haigwood, Oregon Health & Science University; Ann Chahroudi, Emory University; Genevieve G Fouda, Duke University; Sallie R Permar, Duke University
• Language: English
• Date: 2020-05-01
• Publisher: SPRINGER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, Springer Science Business Media, LLC, part of Springer Nature
• Final Published Version (URL): http://dx.doi.org/10.1007/s11904-020-00495-1
• Title of Journal or Parent Work: CURRENT HIV/AIDS REPORTS
• Volume: 17
• Issue: 3
• Start Page: 237
• End Page: 248
• Keywords: DEPENDENT CELLULAR CYTOTOXICITY; Life Sciences & Biomedicine; DNA; Functional cure; Viral remission; Pediatric HIV; Science & Technology; Immune-based therapeutics; BROADLY NEUTRALIZING ANTIBODIES; INFECTION; MONOCLONAL-ANTIBODIES; ACTIVE ANTIRETROVIRAL THERAPY; INFANTS; VIROLOGICAL CONTROL; CD8(+) T-CELLS; Infectious Diseases; RESPONSES

Abstract

Purpose of Review: In the absence of antiretroviral therapy (ART), more than 50% of perinatally HIV-infected children die by 2 years of age. Early ART from infancy is therefore a global recommendation and significantly improves immune health, child survival, and disease outcome. However, even early treatment does not prevent or eradicate the latent reservoir necessitating life-long ART. Adherence to life-long ART is challenging for children and longstanding ART during chronic HIV infection led to higher risks of non-AIDS co-morbidities and virologic failure in infected children. Thus, HIV-infected children are an important population for consideration for immune-based interventions to achieve ART-free remission and functional cure. This review summarizes how the uniqueness of the early life immune system can be harnessed for the development of ART-free remission and functional cure, which means complete virus control in absence of ART. In addition, recent advances in therapeutics in the HIV cure field and their potential for the treatment of pediatric HIV infections are discussed. Recent Findings: Preclinical studies and clinical trials demonstrated that immune-based interventions target HIV replication, limit size of virus reservoir, maintain virus suppression, and delay time to virus rebound. However, these studies have been performed so far only in carefully selected HIV-infected adults, highlighting the need to evaluate the efficacy of immune-based therapeutics in HIV-infected children and to design interventions tailored to the early life maturing immune system. Summary: Immune-based therapeutics alone or in combination with ART should be actively explored as potential strategies to achieve viral remission and functional cure in HIV-infected pediatric populations.