Miranda Smith
HIV cure research strategy launched
21st International AIDS Conference (AIDS 2016), Durban, South Africa. Photo shows Steven Deeks, Towards a HIV Symposium Co-Chair, speaking at the Towards an HIV Cure Press Conference. Photo©International AIDS Society/Steve Forrest/Workers’ Photos
An updated scientific strategy towards an HIV cure was released on the eve of the 21st International AIDS Conference in Durban, South Africa. The strategy was developed over 2 years by a broad group of international experts including basic scientists, clinical researchers, social scientists and ethicists. The resulting International AIDS Society Global Scientific Strategy: Towards an HIV Cure 2016 highlights gaps in current HIV cure research and makes concrete recommendations for progress in seven key areas. Here we summarise the recommended directions in each of the seven areas.
1. Molecular biology of HIV latency
This area focusses on the molecules and mechanisms involved in establishing and maintaining latent HIV infection. A lot of progress has already been made in this area, but the strategy identifies four issues needing further investigation. These are:
- Developing lab models of infection reflecting the diversity of latently infected cells in people living with HIV.
- Using new strategies to explore and better understand latently infected cells – for example, strategies that look at a single cell at a time.
- Exploring the contribution of naturally occurring proteins that interfere with HIV infection (HIV restriction factors), including how these proteins control the formation and ongoing maintenance of latent infection.
- Developing better ways to measure and analyse latent infection in cells from people living with HIV.
2. Immunology of HIV persistence
HIV infection damages the immune system right from the beginning, and while antiretroviral therapy goes a long way to minimising the damage, HIV remains in the body. Understanding how the ongoing presence of HIV impacts on the immune response, and exactly what type of immune response may be needed to get rid of HIV are still open questions. The strategy identifies four major priorities for research in this area:
- Understanding where replication-competent HIV is found throughout the body by studying a wide range of adults and children with HIV infection.
- Characterising how the immune environment affects the HIV reservoir, including its size, distribution and ability to be reactivated
- Determining how drugs that modify the immune response affect latent HIV.
- Developing and testing drugs to boost the immune system to either get rid of virus-producing cells during antiretroviral treatment, or control HIV replication if antiretroviral treatment is stopped.
3. Models for HIV cure or sustainable remission
Interventions to induce either HIV cure or long term remission (control of HIV infection in the absence of antiretroviral therapy) will need to be tested in animal models, and ultimately also in human populations. These tests raise important ethical issues since they will need to grapple with strategies that either have unknown safety profiles, or which pose known safety risks to participants, and which may offer only limited benefit on an individual level. Four research priorities are outlined to guide developments in this area:
- Establishing a shared definition of the term ‘HIV remission’ in both clinical research and community settings, and prioritising the use of this term rather than ‘cure’
- Understanding how the timing of antiretroviral therapy impacts on HIV persistence by carefully and systematically studying both the virus and the host immune response at the time that therapy is started
- Developing robust and ethical animal and clinical studies for exploring HIV reservoirs and changes occurring to these reservoirs in response to planned interventions, including the evaluation of candidate biomarkers for predicting if HIV will re-emerge
- Carefully weighing the possibility of gaining useful scientific knowledge against the interests of study participants when designing studies to test testing invasive or potentially risky interventions
4. Remission in the paediatric population
A staggering number of new HIV infections in children every year and the prospect of an entire lifetime on antiretroviral treatment makes achieving HIV remission a priority for children. The strategy outlines the following priorities for research in paediatric populations:
- Understanding how the immune system and its components develop in children
- Exploring how latent reservoirs are established and maintained in children
- Understanding immune responses against HIV that exist before infection, and how these and other strategies to manipulate the immune response might be used to eliminate latently infected cells
- Establishing ethical frameworks for conducting HIV cure research in children
5. Gene and cell therapy
The curing of the Berlin patient, Timothy Brown, through a stem cell transplant with HIV resistant cells has opened the door to exploring multiple strategies for gene and cell therapy. Strategies include making cells resistant to HIV, removing integrated HIV from infected cells, and enhancing cells’ ability to recognise and destroy HIV infected cells. Recommendations for further research in this area include:
- Exploring the potential of engineered T cells to destroy HIV-infected cells
- Improving ways to deliver modifying strategies specifically to latently infected cells
- Testing strategies to boost immune responses in combination with gene/cell therapies
- Understanding the consequences of conditioning strategies used prior to transplantation and developing safer alternatives
6. Novel biomarkers to quantify HIV persistence
Any strategy to reduce latent HIV needs reliable methods to assess effectiveness through measuring HIV persistence. It is critical to estimate how much virus may re-emerge and cause ongoing infection after an intervention. There is currently no consistent marker for predicting how long it will take for virus to re-emerge if treatment is stopped. Research priorities identified in this area are:
- Determining the performance characteristics of all ways of measuring potential biomarkers in a systematic way
- Developing sample repositories and databases to validate any proposed markers for the duration of HIV remission when antiretroviral treatment is stopped
- Assessing biomarkers of HIV persistence in different populations, including children, women, the elderly, and the transgender community
- Using technological advances in a variety of fields to identify new potential biomarkers of viral persistence and latently-infected cells
7. Social science and health systems research
Recognising the complexities of both the HIV epidemic, and efforts to progress towards a cure, the IAS strategy includes priorities for social science and health systems research. Social science research can inform community engagement strategies, contribute to the ethical design and conduct of clinical trials and potentially limit unintended outcomes of cure interventions. Health systems research can contribute to policy relevance, health systems preparedness and facilitate public-private collaboration. In these areas, the strategy identifies the following priorities:
- Identifying and understanding the perceptions, attitudes and beliefs around HIV cure of people living with HIV, their partners and communities
- Measuring and promoting engagement from a diverse range of individuals from many local contexts in HIV cure research
- Using analytic strategies to optimise clinical trials and demonstrate the financial impact of cure strategies
- Determining optimal health systems and policies for promoting HIV cure research
Developed by an impressive range of world-class researchers, the global scientific strategy provides a robust, comprehensive and state-of-the-art framework for future HIV cure research.
The strategy has been published in the journal Nature Medicine
The full recommendations from the International AIDS Society Towards a Cure Working Group can be found here
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