Advancements in Developing Strategies for Sterilizing and Functional HIV Cures.

Wei Xu,Haoyang Li,Hanzhen Zhang,Chen Hua,Lu Lu,Shibo Jiang,Qian Wang,Weihua Li

doi:10.1155/2017/6096134

Abstract

Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4+ T cells. Currently, two types of HIV cures are in development: a “sterilizing cure” and a “functional cure.” A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment. Based on these concepts, significant progress has been made in different areas. This review focuses on recent advancements and future prospects for HIV cures.

Highlights

Combined antiretroviral therapy has enabled the sustained control of viremia in virtually all human immunodeficiency virus (HIV) patients
We proposed that an HIV prophylactic and therapeutic vaccine could be designed by combining anti-α4β7 monoclonal antibody (mAb) with a V2-containing antigen in gp120 for induction of strong V2-specific antibody responses against HIV-1 infection because (1) both V2-specific B cell receptor (V2-BCR) and α4β7 integrin are expressed on B cells; (2) binding of V2-containing antigen to α4β7 integrin would block its binding to V2-BCR; and (3) blocking V2-containing antigen binding to α4β7 integrin by anti-α4β7 mAb would allow the V2-containing antigen to bind with V2-BCR on B cells to induce V2-specific antibody responses against HIV-1 infection [61]
The above findings suggest that a CD4 molecule, CD4 domain, or small-molecule CD4 mimetic can trigger the HIV-1 Env conformation change, resulting in the exposure of some conserved epitopes or region in gp120 or gp41, which can serve as a target for antibodies with a neutralizing effect of antibody-dependent cellular cytotoxicity (ADCC) effect, or for peptide-based HIV-1 fusion inhibitors, such as enfuvirtide

Summary

Introduction

Combined antiretroviral therapy (cART) has enabled the sustained control of viremia in virtually all human immunodeficiency virus (HIV) patients. It has prolonged lifespan, improved quality of life, and transformed HIV infection from a fatal disease into a chronic infectious disease [1,2,3]. It is very difficult to find donors with human leukocyte antigens (HLA) identical to those of recipients for CCR5 Delta32/Delta stem cell transplantation, while the mortality rate of transplant surgery is up to 30%. The human genome has integrated a large number of retrotransposon sequences over the course of evolution, and HIV may coexist with humans if it is restricted From this perspective, the functional cure is as important as the sterilizing cure. This article will review the advancements in developing strategies for both sterilizing and functional HIV cures

Strategies for Sterilizing HIV Cure

Strategies for Functional Cure

Findings

Conclusion