Abstract
A functional Human immunodeficiency Virus (HIV) cure has been proposed as an alternative to antiretroviral treatment for life, and therapeutic vaccines represent one of the most promising approaches. The goal of therapeutic vaccination is to augment virus-specific immune responses that have an impact on HIV viral load dynamics. To date, the agreed feature to evaluate the effects of these therapeutic interventions is analytical antiretroviral treatment interruption (ATI), at least until we find a reliable biomarker that can predict viral control. Different host, immunologic, and virologic markers have been proposed as predictors of viral control during ATI after therapeutic interventions. This review describes the relevance of ATI and the different surrogate markers of virological control assessed in HIV therapeutic vaccine clinical trials.
Highlights
Antiretroviral therapy (ART) is effective in maintaining viral suppression and reducing morbidity and mortality in patients with Human Immunodeficiency Virus (HIV) infection
Lévy et al described that vaccination with ALVAC vCP1433 and HIV-LIPO-6T + IL-2 markedly increased the percentage of patients who responded to HIV antigens as compared with non-vaccinated patients and in previous studies, where both HIV-1 specific CD4+ lymphoproliferative responses (LPR) and breadth of HIV-specific CD8+ T cell immune responses resulted in a positive correlation with time off treatment after antiretroviral treatment interruptions (ATI) [43]
Data addressing whether soluble inflammation markers could influence viral control dynamics after ATI has been assessed in a peptide-based therapeutic HIV-1 p24 Gag vaccine candidate (Vacc4x clinical trial)
Summary
Antiretroviral therapy (ART) is effective in maintaining viral suppression and reducing morbidity and mortality in patients with Human Immunodeficiency Virus (HIV) infection. A second individual receiving a hematopoietic stem cell transplant with the same mutation has recently been cured as his HIV viral load remains 30 months after ART interruption [4] This treatment involves a high risk of mortality and is only used in patients who have life-threatening hematological malignancies. A functional cure is the generation of an efficient host immunity capable of suppressing HIV replication in the absence of ART This field currently lacks non-viral biomarkers of reservoir reduction or virologic control, requiring analytical antiretroviral treatment interruptions (ATI) to assess in-vivo efficacy of interventions aiming to achieve ART-free HIV remission [5]. ATI are only justifiable if the participant understand the risks, and if there is a scientific question that cannot be solved efficiently by any other means [5]
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