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

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. 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.

Keywords: Functional cure; Immune-based therapeutics; Pediatric HIV; Viral remission.

Fig 1.

Timing for immune therapeutic interventions in HIV-infected children. In utero infection and breast feeding period provide a unique early intervention opportunity using combination of ART and passive adminstration of bNAbs to supress viremia and limit establishment of latent virus resevoir as well as virus diversity. During the main window of opportunity (from 2 to 9 years of age), children’s immune ontogeny favors the developemnt of cell-mediated immunity that is likely to play a major role in eradication of HIV infection. Late immune therapeutic interventions provide further potentials to achive virus control, remission, and functional cure prior to sexual debut as well as ART interruption. Created with BioRender.