Controversies in the Design of Strategies for the Cure of HIV Infection

Abstract

The cure for chronic human immunodeficiency virus (HIV) infections has been a goal pursued since the antiretroviral therapy that improved the clinical conditions of patients became available. However, the exclusive use of these drugs is not enough to achieve a cure, since the viral load rebounds when the treatment is discontinued, leading to disease progression. There are several theories and hypotheses about the biological foundations that prevent a cure. The main obstacle appears to be the existence of a latent viral reservoir that cannot be eliminated pharmacologically. This concept is the basis of the new strategies that seek a cure, known as kick and kill. However, there are other lines of study that recognize mechanisms of persistent viral replication in patients under effective treatment, and that would modify the current lines of research on the cure of HIV. Given the importance of these concepts, in this work, we propose to review the most recent evidence on these hypotheses, covering both the evidence that is positioned in favor and against, trying to expose what are some of the challenges that remain to be resolved in this field of research.

Harnessing Autophagy to Overcome Antigen-Specific T-Cell Dysfunction: Implication for People Living with HIV-1

“…Despite the success of ART in fully suppressing viral replication in plasma, HIV-1 remains an incurable infection. A cure for HIV-1, which represents the next objective in therapeutic research, is defined as a durable control of viral replication in the absence of ART [ 30 , 31 ]. Therefore, natural control of HIV-1 remains one of the most promising models for a cure, since elite controllers (EC) represent a unique HIV-1-infected and ART-naïve group of individuals who are defined by replication-competent virus control along with effective and persistent Ag-specific T-cell immune responses for years [ 32 , 33 , 34 , 35 ].…”