Karine Dubé

The International AIDS Society (IAS) held a virtual pre-conference meeting titled Pathways to an HIV Cure: Tools for Community and Clinicians, held July 1–3. The meeting focused on research developments, challenges of HIV cure clinical trials, and strategies for low and middle-income countries. Following are a few highlights.

Michael Louella from the defeatHIV Collaboratory Community Advisory Board in Seattle, Washington, discussed the need to better understand community attitudes and values to achieve an HIV cure. Louella recommended moving from a deficit approach to an asset approach that starts with meaningfully engaging the community. Louella added that it will be critical to understand the perspectives of HIV care teams in the search towards an HIV cure.

Dr. Jillian Lau from the Alfred Health and Monash University in Australia discussed community and clinician perspectives around HIV treatment interruptions. Dr. Lau recently completed a global survey on attitudes towards HIV treatment interruptions in people living with HIV and HIV care providers. Dr. Lau emphasized the need for targeted educational and community engagement materials. Barriers to HIV cure research participation—such as risk of transmission, and PrEP provision and counseling for sexual partners—will also need to be addressed.

Dr. Sarah Fidler from the Imperial College London reviewed challenges in HIV cure clinical studies. An important challenge will be determining when will it be considered safe to resume clinical studies given the ongoing COVID-19 pandemic. Dr. Fidler’s recommendations were to exclude participants who have a potentially increased risk of severe COVID-19 disease (e.g. diabetes, high BMI and older age). Dr. Fidler also emphasized the important role of community consultation in defining acceptable clinical trial parameters during the COVID-19 pandemic to reduce unnecessary risks and burdens.

Professor Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Australia, and Dr. John Frater [from Oxford University, England, squared off in a debate titled, Gene Therapy versus Immunotherapy—Which is More Likely to Work? Dr. Lewin presented five arguments for gene therapy: 1) studies should be aimed at complete elimination of HIV in the body—not remission; 2) there is proof of concept for the elimination of the CCR5 towards an HIV cure—with the Berlin Patient, Timothy Ray Brown and the London Patient, Adam Castillejo; 3) there are multiple gene therapy candidates in the pipeline; 4) the potential for ease of delivery; and 5) improvements in reducing complexity, toxicity, and cost of gene therapy approaches. Dr. Frater presented the argument towards immunotherapy, or drugs that could enhance the immune system. Examples include broadly neutralizing antibodies (bNABs) and chimeric antigen receptor (CAR) T cells. Immunotherapy could be used in thousands (or even millions of people), is relatively safe, and could eventually allow people living with HIV to stop their antiretroviral therapy and stay well.

Dr. Thumbi Ndung’u from the Africa Health Research Institute (AHRI) in South Africa provided an overview of HIV cure research relevant to resource-limited settings. HIV cure research will need to include high-burden settings in the future. Further, the need for a cure is justified by the high incidence of HIV and presence of significant HIV-associated multi-morbidities, such as cardiovascular disease, metabolic disorders, neurocognitive abnormality, and malignancies. Promising HIV cure strategies in development include early treatment, immune modulation, gene editing, and combination approaches. Dr. Ndung’u and Dr. Steve Deeks, professor of medicine at the University of California San Francisco (UCSF), announced a new initiative with the Bill and Melinda Gates Foundation aimed at developing a target product profile (TPP) to guide the development of HIV cure strategies relevant to low- and middle-income countries and align stakeholders in defining acceptable HIV cure research regimens. An ideal HIV cure product should be safe and effective (comparable to, if not better than, antiretroviral treatment), scalable and affordable, able to prevent re-infection, and work in all populations.

Karine Dubé is an assistant professor at the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. She is a socio-behavioral scientist focused on integrating a patient/participant perspective to HIV cure-related research.