Abstract
Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART) but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs) with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.
Highlights
Since 1983, human immunodeficiency virus type 1 (HIV-1) has been a worldwide epidemic, with reportedly more than 35 million people living with HIV-1 globally and 2.1 million newly infected each year
While most antivirals against HIV-1 approved by the Food and Drug Administration are reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs), the integrase inhibitors (INIs) have become a prominent class of antivirals [1]
Because of the high variability of HIV-1 envelope glycoprotein spike (Env) and the unique properties required of a broadly neutralizing antibodies (bNAbs), the development of rare bNAbs for chronically HIV-1-infected individuals may take several years
Summary
Since 1983, human immunodeficiency virus type 1 (HIV-1) has been a worldwide epidemic, with reportedly more than 35 million people living with HIV-1 globally and 2.1 million newly infected each year. Because of the high variability of HIV-1 Env and the unique properties required of a bNAb, the development of rare bNAbs for chronically HIV-1-infected individuals may take several years Such bNAbs will play a significant role in guiding the new structure-based immunogen designs and contribute to both HIV-1 prevention and treatment fields. In latest progress on anti-HIV therapy, Byrareddy et al reported that the combination of antiretroviral and α4β7 antibody therapy could effectively control viremia and reconstitute immune systems in macaques infected with simian immunodeficiency virus (SIV) This occurred during the combinatorial treatment period and even after the treatment was terminated [16], indicating that the antibody is targeting the integrin in CD4+ T cells (α4β7) instead of bNAbs directed to the virus per se. The CD4-binding site on the Env trimer could be an ideal target for vaccine design
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