Abstract
Increasing numbers of HIV-infected individuals have access to potent antiretroviral drugs that control viral replication and decrease the risk of transmission. However, there is no cure for HIV and new strategies have to be developed to reach an eradication of the virus or a natural control of viral replication in the absence of drugs (functional cure). Therapeutic vaccines against HIV have been evaluated in many trials over the last 20 years and important knowledge has been gained from these trials. However, the major obstacle to HIV eradication is the persistence of latent proviral reservoirs. Different molecules are currently tested in ART-treated subjects to reactivate these latent reservoirs. Such anti-latency agents should be combined with a vaccination regimen in order to control or eradicate reactivated latently-infected cells. New in vitro assays should also be developed to assess the success of tested therapeutic vaccines by measuring the immune-mediated killing of replication-competent HIV reservoir cells. This review provides an overview of the current strategies to combine HIV vaccines with anti-latency agents that could act as adjuvant on the vaccine-induced immune response as well as new tools to assess the efficacy of these approaches.
Highlights
Despite the undeniable success of antiretroviral therapy (ART) in limiting HIV replication, it has become increasingly evident that ART is not a long-term solution for HIV-infected individuals.Besides the deleterious side effects, ART does not eradicate HIV and does not optimally reconstitute the immune system [1,2]
Functional cure from HIV infection was achieved for the first time by Timothy Brown, the Berlin patient, who was given hematopoietic stem cell transplant (HSC) from CCR5 delta 32 donor [14]
We have previously shown a marked degree of clonotypic turnover within HIV-specific CD8+ T cell populations as a consequence of antigen decay after the initiation of ART with particular clonotypes selected for their higher functional sensitivity [42]
Summary
Despite the undeniable success of antiretroviral therapy (ART) in limiting HIV replication, it has become increasingly evident that ART is not a long-term solution for HIV-infected individuals. Eradication strategy aims at the induction of viral replication in latently-infected cells and at the elimination of these reactivated cells by either direct cytolytic targeting or by immunotherapeutic intervention [11]. Dr Siliciano’s group showed that after in vitro expansion of HIV-specific CD8+ T cells from ART-treated subjects, these cells were able to eliminate HIV-infected CD4+ T cells [12] This seminal study provided the rationale for new therapeutic strategies that combine agents that reactivate latently-infected CD4+ T cells with immune interventions that increase the numbers and function of HIV-specific CD8+ CTLs to clear HIV reservoirs in individuals on ART. Different approaches are currently being tested to reactivate latently-infected cells and restore immune functions. This review will describe the current knowledge and advances using these therapeutic strategies
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