In one study involving chronically HIV-infected patients, MMF was found to reduce the size of dividing CD4+ T cells and the reduction was found only to be correlated with viral replication in patients who maintained the capacity to inhibit lymphocyte proliferation (61). 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 Amotosalen hydrochloride and clinical trials exhibited 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. and in Amotosalen hydrochloride early life establishes a highly tolerogenic and broadly anti-inflammatory immune environment that may influence the efficacy of immune interventions towards a functional HIV cure in pediatric populations. Some of the unique aspects of the early life immune system that may favor HIV cure include: (1) the tolerogenic immune environment, which promotes low immune activation (19, 20) that contributes to the low expression of the HIV co-receptor CCR5 in memory CD4+ T cells, thus could limit the establishment of latent virus reservoir (24); and (2) the unbiased CD8+ T cell repertoires that generate autologous variant-specific anti-HIV cytotoxic T lymphocytes (CTL) responses early in HIV-infected children (25). The immune system in utero and in early life favors low levels of immune activation, at least initially, following HIV contamination but is then skewed towards increased immune activation associated with increased viral reservoir size, viral replication, microbial translocation, and mucosal inflammation as the disease progresses. The overall balance between these opposing influences may depend crucially around the timing of ART initiation. Early ART initiation will minimize the size of the latent viral reservoir as well as chronic immune activation and MYCN provide an opportunity for introduction of immune therapeutic interventions. Despite lack of HIV-specific immunity in infants who are treated early with ART, they appear to maintain normal immune system development and more active thymus (26), suggesting the potential for therapeutic vaccines that control latent or persistent HIV reservoir in the absence of ART. Differences in Amotosalen hydrochloride pathogenesis between HIV infected adults and children may also enhance the potential for a cure in HIV-infected neonates. The latent virus reservoir in HIV-infected infants is more homogeneous than in adults as it has not been selected by CTL and other immunologic pressures (27). Importantly, the rate of cell-associated virus decay following very early ART initiation is faster in infants than in early-treated children and adults, and the decrease in virus reservoir size continues for a longer time period of time in children as compared to adults (28C31). Recent studies have reported that HIV-infected infants develop bNAb responses earlier and more frequently than untreated HIV-infected adults, suggesting that this immune response could be harnessed in immune strategies towards a cure (32, 33). Importantly, although infants showed a delay in the development of antibodies capable of mediating antibody-dependent cellular Amotosalen hydrochloride cytotoxicity (ADCC), these effector functions are associated with a better disease outcome in HIV-infected infants, suggesting the ability to mediate clearance of HIV-infected cells (34, 35). Altogether, these observations provide a strong rationale for the development of strategies that harness the uniqueness of the early life immune system for the remission and/or eradication of HIV in children. Immunomodulatory brokers as adjunctive HIV treatment HIV contamination, in the absence of ART, results in profound.