Immunotherapeutic Approaches to HIV Cure and Remission

Ming J. Lee; S. Fidler; John Frater

Disclosures

Curr Opin Infect Dis. 2022;35(1):31-41. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: Despite improvements in the effectiveness of antiretroviral therapy (ART), there are still unmet needs for people living with HIV which drive the search for a cure for HIV infection. The goal of this review is to discuss the challenges and recent immunotherapeutic advances towards developing a safe, effective and durable cure strategy for HIV.

Recent Findings: In recent years, advances have been made in uncovering the mechanisms of persistence of latent HIV and in developing more accurate assays to measure the intact proviral reservoir. Broadly neutralising antibodies and modern techniques to enhance antibody responses have shown promising results. Other strategies including therapeutic vaccination, latency reversal agents, and immunomodulatory agents have shown limited success, but newer interventions including engineered T cells and other immunotherapies may be a potent and flexible strategy for achieving HIV cure.

Summary: Although progress with newer cure strategies may be encouraging, challenges remain and it is essential to achieve a high threshold of safety and effectiveness in the era of safe and effective ART. It is likely that to achieve sustained HIV remission or cure, a multipronged approach involving a combination of enhancing both adaptive and innate immunity is required.

Introduction

Improvements in antiretroviral therapy (ART) have led to excellent prognosis for people living with HIV (PWH), preventing onward transmission and disease progression. Despite these advances, there are still unmet needs for PWH which drive the search for a cure. Most ART is oral medication requiring daily adherence. Stigma and treatment fatigue associated with taking daily ART remains a concern for many people with HIV.[1] Although the development of long-acting ART may address some of these issues, nonadherence or delayed doses leading to treatment resistance remains an issue, and the costs of delivery may still prove prohibitive particularly in resource-limited settings.[2] Thus the search for a cure remains a priority. A cure may be 'functional', where there is long-term control of HIV replication without treatment, or 'sterilising', where there is complete elimination of HIV provirus from the body.

Cure strategies can be divided into two basic approaches – targeting the provirus directly, or enhancing HIV-specific immunity. The former approach which includes aiming to limit the size or characteristics of the HIV reservoir, preventing viral replication, and silencing of the HIV provirus ('block and lock'), is covered in a recent review by Vansant et al.,[3] and will not be covered further here.

In this review, we will discuss developments in immunotherapeutic approaches to enhance HIV-specific immune responses, as summarised in Figure 1.

Figure 1.

Diagram summarising immunotherapeutic strategies targeting the latent HIV reservoir.

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