Multi-stakeholder consensus on a target product profile for an HIV cure

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

Multi-stakeholder consensus on a target product profile for an HIV cure

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

IAS Towards an HIV Cure Symposium: people focused, science driven: 18-19 July 2015, Vancouver, Canada.

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

The binding of platinum hexahalides (Cl, Br and I) to hen egg-white lysozyme and the chemical transformation of the PtI6 octahedral complex to a PtI3 moiety bound to His15

This study examines the binding and chemical stability of the platinum hexahalides K(2)PtCl(6), K(2)PtBr(6) and K(2)PtI(6) when soaked into pre-grown hen egg-white lysozyme (HEWL) crystals as the protein host. Direct comparison of the iodo complex with the chloro and bromo complexes shows that the iodo complex is partly chemically transformed to a square-planar PtI(3) complex bound to the N(δ) atom of His15, a chemical behaviour that is not exhibited by the chloro or bromo complexes. Each complex does, however, bind to HEWL in its octahedral form either at one site (PtI(6)) or at two sites (PtBr(6) and PtCl(6)). As heavy-atom derivatives of a protein, the octahedral shape of the hexahalides could be helpful in cases of difficult-to-interpret electron-density maps as they would be recognisable ‘objects’

Research priorities for an HIV cure : International AIDS Society Global Scientific Strategy 2021

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. An effective and scalable cure strategy is a top priority for the HIV research field; this Review discusses recent advances, knowledge gaps, and priority research areas for the next 5 years

Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021

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.Fil: Deeks, Steven G.. University of California; Estados UnidosFil: Archin, Nancie. University of North Carolina; Estados UnidosFil: Cannon, Paula. University of Southern California; Estados UnidosFil: Collins, Simon. Hiv I-base; Reino UnidoFil: Jones, R. Brad. Cornell University; Estados UnidosFil: de Jong, Marein A. W. P.. Aidsfonds; Países BajosFil: Lambotte, Olivier. Universite Paris-Saclay;Fil: Lamplough, Rosanne. International AIDS Society; SuizaFil: Ndung’u, Thumbi. University College London; Estados Unidos. Ragon Institute of MGH; Estados Unidos. University of KwaZulu-Natal; SudáfricaFil: Sugarman, Jeremy. University Johns Hopkins; Estados UnidosFil: Tiemessen, Caroline T.. University of the Witwatersrand; SudáfricaFil: Vandekerckhove, Linos. University of Ghent; BélgicaFil: Lewin, Sharon R.. The Peter Doherty Institute For Infection And Immunity; Australia. Monash University; Australia. University of Melbourne; AustraliaFil: Deeks, Steven. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: de Jong, Marein. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Ndhlovu, Zaza. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Chomont, Nicolas. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Brumme, Zabrina. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Deng, Kai. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Jasenosky, Luke. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Jefferys, Richard. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Orta Resendiz, Aurelio. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Mardarelli, Frank. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Nijhuis, Monique. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Bar, Katharine. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Howell, Bonnie. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Schneider, Alex. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Nabatanzi, Rose. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Blankson, Joel. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados Unido