ABSTRACT
Despite the success of antiretroviral therapy (ART) for people living with HIV, lifelong treatment is required and there is no cure. HIV can integrate in the host genome and persist for the life span of the infected cell. These latently infected cells are not recognized as foreign because they are largely transcriptionally silent, but contain replication-competent virus that drives resurgence of the infection once ART is stopped. With a combination of immune activators, neutralizing antibodies, and therapeutic vaccines, some nonhuman primate models have been cured, providing optimism for these approaches now being evaluated in human clinical trials. In vivo delivery of gene-editing tools to either target the virus, boost immunity or protect cells from infection, also holds promise for future HIV cure strategies. In this Review, we discuss advances related to HIV cure in the last 5 years, highlight remaining knowledge gaps and identify priority areas for research for the next 5 years.
Subject(s)
HIV Infections/therapy , Research , Societies, Medical , HumansABSTRACT
Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures.
Subject(s)
HIV Infections/epidemiology , Antiretroviral Therapy, Highly Active , Combined Modality Therapy , Consensus , Disease Management , Expert Testimony , HIV , HIV Infections/drug therapy , HIV Infections/virology , Humans , Public Health SurveillanceABSTRACT
The International AIDS Society (IAS) convened the Towards an HIV Cure Symposium on 18-19 July 2015 in Vancouver, Canada, bringing together researchers and community to discuss the most recent advances in our understanding of HIV latency, reservoirs and a summary of the current clinical approaches towards an HIV cure. The symposium objectives were to: (1) gather researchers and stakeholders to present, review, and discuss the latest research towards an HIV cure; (2) promote cross-disciplinary global interactions between basic, clinical and social scientists; and (3) provide a platform for sharing information among scientists, clinicians, funders, media and civil society. The symposium examined basic molecular science and animal model data, and emerging and ongoing clinical trial results to prioritise strategies and determine the viral and immune responses that could lead to HIV remission without antiretroviral therapy. This report summarises some of the major findings discussed during the symposium.
