James McMahon

This cross cutting session involved community, basic scientists and clinical researchers. Examination of cell based and animal models to test interventions that may enter the clinic were reviewed and also 2 prominent strategies examined in clinical studies, latency reversal and stem cell transplantation were reviewed.

The session began with community advocate Jeff Taylor describing how the driver for HIV cure is HIV-associated stigma, as Jeff stated, ‘We can’t treat our way out of this epidemic” and “The cure for stigma is a cure for HIV”. Then followed early data from a cell based model demonstrating how Staph aureus can stimulate dendritic cells and antigen (Staph aureus) specific CD4+ T-cells to upregulate CCR5 and alpha-4 beta-7 making these cells susceptible to HIV infection. Next, Thomas Rasmussen reviewed latency reversal trials and agents with HIV-specific latency reversal, specifically a cell model to screen drug compounds for upregulation of HIV-specific transcription and agents typically thought of as immune modulators having potential for HIV latency reversal (TLR agonists and immune checkpoint blockers). Finally, updates on stem-cell transplantation and updates on the London and Dusseldorf patients who are now without viral rebound for 22 and 8 months respectively.

Driven by a strong desire for HIV cure from the community, investigators are employing a broad array of innovative approaches to this challenge in the laboratory and the clinic. This session highlights how initial observations can be extended to devise a path to cure. Examples include development of models to understand how commonly occurring infections can drive HIV persistence, further investigation of the mechanisms by which immune modulators may impact the HIV reservoir and how the initial case of cure in The Berlin patient have been extended to other individuals in the ICISTEM cohort.

Angela Wahl

The following key topics in HIV cure research were covered: 1) why HIV cure is important to HIV-positive people, 2) the interplay between myeloid and CD4+ T cells, 3) approaches for HIV latency reversal, 4) animal models for HIV cure research, and 5) HIV cure by stem cell transplantation.

Jeff Taylor indicated that the top reason HIV cure is important to HIV-positive people is due to the stigma associated with being HIV-positive. Eric Cohen showed that S. aureus promotes RALDH2 activity in MDDC and a CCR5+ITGβ7+ phenotype in co-cultured CD4+ T cells and that MDDC trans-infect S. aureus-specific CD4+ T cells via a RALDH2/retinoic acid-dependent mechanism. Thomas Rasmussen summarized the in vivo efficacy of latency reversing agents to induce HIV expression and proposed that differences in study designs (e.g. romidepsin clinical trials) could affect the magnitude of the effect observed. Victor Garcia demonstrated how humanized mouse and non-human primate models of HIV/SIV can guide and compliment each other as observed with the in vivo testing of the latency reversing agent AZD5582. Monique Nijhuis introduced ICISTEM, an international collaboration to guide and investigate the potential for HIV cure in HIV-infected patients requiring allogeneic stem cell transplantation for hematological disorders.

The stigma associated with being HIV-positive is a key motivator for HIV-positive people to participate in HIV cure trials, even if they won’t experience a direct benefit. Careful attention must be paid to the design of HIV clinical trials and animal studies to ensure that outcomes are reliable and reproducible, ensuring confidence in their efficacy and safety. While the only HIV cure in a person to date was through stem cell transplantation, this approach may not be scalable to the global population. Stem cell transplantation combined with genome editing could extend the reach of this approach to more HIV-positive people.