Broadly neutralizing antibody and the HIV reservoir in acute HIV infection: a strategy toward HIV remission?

Abstract

Purpose of review: Infection of long-lived CD4 T cells is a major obstacle to HIV remission, and antiretroviral therapy (ART) instituted during acute HIV infection restricts HIV reservoir establishment. Broadly neutralizing antibodies (bNAbs) may be employed in conjunction with early ART as strategies toward HIV remission.

Recent findings: Proof-of-concept studies in vitro and in animal models demonstrated bNAbs' ability to block viral entry into cells, suppress viremia and reduce cell-associated viral DNA. Combination bNAbs were more effective than single bNAb in suppressing viremia. When bNAb was used with ART with or without combination latency reversing agents, it prevented viral rebound after ART interruption in at least half of the animals. In one study, macaques with low baseline viral load achieved viral remission even after the blood bNAb titer was no longer detected.

Summary: The acute HIV infection period represents a unique opportunity to explore the use of bNAbs with ART to limit the reservoir seeding that may enhance the chance of HIV remission. This article discusses the effects of early ART and bNAbs on HIV reservoirs and proposes research strategies in acute HIV infection aiming at HIV reservoir reduction and HIV remission.

FIGURE 1

Proposed research strategies for using broadly neutralizing antibody (bNAb) in acute HIV infection. In the typical course of HIV infection (grey line), HIV RNA peaks during acute infection, penetrates various body compartments to establish a latent reservoir, and ultimately reaches a steady level of viremia. Antiretroviral therapy (ART) initiated during chronic infection reduces HIV RNA, often to undetectable levels, but the virus rebounds when ART is stopped. bNAbs can be administered with ART during acute infection in order to possibly achieve a more rapid viral suppression (black line) and prevent establishment of a significant HIV reservoir. In people treated with ART during acute HIV infection, bNAbs could be given in attempt to eliminate HIV-infected cells to an extent that, thereby, viremic control posttreatment interruption can be achieved (dark grey line). It is also possible to give latency reversing agents (LRAs) to reactivate the expression of HIV on infected cells to facilitate the bNAb’s function in eliminating these reactivated cells.