Abstract
Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reservoirs and can result in multiple side effects including the development of multidrug-resistant escape mutants. Antibody-based treatments have emerged as alternative approaches for a HIV-1 cure. Here, we will review clinical advances in coreceptor-targeting antibodies, with respect to anti-CCR5 antibodies in particular, which are currently being generated to target the early stages of infection. Among the Env-specific antibodies widely accepted as relevant in cure strategies, the potential role of those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs) in eliminating HIV-1 infected cells has gained increasing interest and will be presented. Together, with approaches targeting the HIV-1 replication cycle, we will discuss the strategies aimed at boosting and modulating specific HIV-1 immune responses, highlighting the harnessing of TLR agonists for their dual role as latency reverting agents (LRAs) and immune-modulatory compounds. The synergistic combinations of different approaches have shown promising results to ultimately enable a HIV-1 cure.
Highlights
At the end of December 2020, 27.5 million people were accessing antiretroviral therapy (ART), up from 7.8 million in 2010. This life-long treatment reduced new human immunodeficiency virus type 1 (HIV-1) infections by 52% since its peak in 1997 [1], as well as the progression to Acquired Immunodeficiency Syndrome (AIDS) and the complications associated with inflammation [2]
We will focus on coreceptor-targeting antibodies (Abs), those targeting CCR5, and among the Env-specific antibodies, we will point out those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs)
Abs in some subjects was significantly associated with a progression toward disease; conLTNP status persisted in subjects who maintained anti-CCR5 Abs [15]
Summary
At the end of December 2020, 27.5 million people were accessing antiretroviral therapy (ART), up from 7.8 million in 2010 This life-long treatment reduced new human immunodeficiency virus type 1 (HIV-1) infections by 52% since its peak in 1997 [1], as well as the progression to Acquired Immunodeficiency Syndrome (AIDS) and the complications associated with inflammation [2]. HIV-1 infected patients experience non-AIDS diseases including cardiovascular and bone diseases and cognitive disorders [5]. To overcome these barriers, new strategies have been implemented to achieve a more effective curative intervention to eradicate HIV-1. 1. Ninety clinical trials basedareonregistered the targets reported in this
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