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THE EMERGING POTENTIAL FOR HIV CURE FOR INFANTS, CHILDREN, AND ADULTS
U.S. Military HIV Rsr Prog, USA and The Thai Red Cross AIDS Rsr Cntr, Thailand
HIV cure is a desirable goal for children and adults living with HIV who face stigma and life-long antiretroviral therapy (ART) that requires strict adherence. In addition, treatment cost poses a significant burden to national programs and global donors that could be alleviated were a cure available. The ultimate objective is to eliminate all cells capable of producing HIV – a near unattainable goal with current therapies. The field has re-calibrated the HIV cure target to a more achievable one of HIV remission, i.e., the ability to control viral replication after ART interruption to levels below detection. The major obstacle is, however, the seeding of the HIV reservoir that occurs early during acute HIV infection and sets the stage for the establishment of latent reservoirs, particularly in long-lived CD4+ T cells and lymphoid tissues. The unique aspects of the pediatric immune system in the composition of the CD4+ T cell compartment and defense against HIV may influence HIV persistence. Early ART is an important step in the path towards an HIV cure. The pediatric population offers a unique opportunity for immediate treatment because of the known timing of HIV exposure in most newborns. Similarly, acute HIV infection studies have demonstrated the ability to identify and treat very early infection in adults. Both children and adults treated in acute HIV infection achieve significantly smaller HIV reservoirs, preserved immune functions with little viral escape to immune pressure. These qualities could enhance the effects of immune-based interventions aimed at depleting HIV-infected cells. However, despite these favorable qualities, the majority of early treated individuals do not achieve HIV remission. Therefore, additional therapies will be needed that may include latency reversing agents and passive and active immune therapies. There are exciting new developments of broadly neutralizing antibodies and therapeutic HIV vaccines that could be beneficial to HIV cure. It is highly likely that combination therapies that can generate persistent and effective immune responses to control HIV will be required for a durable HIV remission and cure. In this early discovery phase of HIV cure research that is associated with risks and uncertainties, and further complicated by the difficult concepts of remission and cure, it is also important that ethical, behavioral and social research be conducted in parallel to basic and clinical research.