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1 December 2021 (Geneva, Switzerland) – IAS – the International AIDS Society – has launched its latest strategy to find an HIV cure. Research Priorities for an HIV Cure: IAS Global Scientific Strategy 2021, was published today, World AIDS Day, in the journal, Nature Medicine.

The third edition of the IAS strategy comes soon after it was announced that an Argentinean woman, known as the ‘’Esperanza patient’’, had been cured of HIV through natural immunity. This breakthrough has provided new hope for an HIV cure.
 
The curing of Timothy Ray Brown, also known as the “Berlin patient”, of HIV in 2008 inspired the IAS to set up the Towards an HIV Cure programme, founded by HIV co-discoverer and Nobel Laureate Françoise Barré-Sinoussi, in 2010. The aim is to drive concerted efforts to accelerate global scientific research and engagement towards a cure for HIV.
 
At AIDS 2012, the 19th International AIDS Conference, in Washington D.C., the IAS launched the inaugural Towards an HIV cure: A global scientific strategy, which established cure as a pillar of the global HIV response. An updated strategy was released in 2016. The latest iteration comes after a decade of progress, which saw Adam Castillejo (the “London patient”) cured via a stem cell transplant and two women seemingly cured through natural immunity. In addition, several interventions have shown great promise for a cure in animal models of HIV.
 
“It is clear that an HIV cure is achievable. The past five years of following the science have taught us that,” Adeeba Kamarulzaman, President of the IAS and Director of the Centre of Excellence for Research in AIDS at the University of Malaya in Malaysia, said.
 
“The recent case of the cured Esperanza patient adds a new dimension to our understanding of HIV controllers, those people who naturally control HIV without antiretroviral therapy. The challenge is to identify how commonly elimination of all intact virus occurs in elite controllers and what the mechanism is that makes that possible. We can then work out how we can replicate it on a broad scale. We need an HIV cure that works for everyone so we can end the HIV pandemic.
 
“The surfacing of the Omicron SARS-CoV-2 variant is a reminder to us all that vaccine inequity and our failure to end infectious diseases, such as HIV and tuberculosis, are the same side of the coin – a devaluation of human life in poor countries.’’
 
A 68-member IAS International Scientific Working Group developed the 2021 strategy over a year. The strategy reflects on progress made, identifies gaps in the research agenda, and outlines recommendations for HIV cure research over the next five years.

What we’ve learnt:

• Several instances of remission and eradication have been recorded. Research towards an HIV cure is looking at these people, as well as HIV controllers, to better understand how a cure could work and help identify targets for HIV cure-related interventions.
• Research on HIV controllers has provided new information and directions for cure research.
• HIV reservoirs (cells that are the source of HIV once antiretroviral therapy, or ART, is stopped) are now seen as evolving rather than static sources of HIV not reached by ART. Important differences among people with HIV have been identified, such as biological sex, which affect reservoir location and dynamics.
• Technological developments allow for a better understanding of how HIV latency is established and how the virus is reactivated after an analytical treatment interruption (conducted in the context of HIV cure research). This allows for the identification of new targets for HIV cures.
• New drugs and interventions are being developed and have started to show success in animal (preclinical) models.

The key to a cure: the HIV reservoir

“Over the last decade, HIV cure research has greatly intensified but it remains clear that we will not cure HIV until we better understand where and how the virus hides. There has been substantial progress but more fundamental research is still needed,” Professor Sharon Lewin, Co-Chair of the IAS Towards an HIV Cure programme, President-Elect of the IAS and Director of the Peter Doherty Institute for Infection and Immunity in Australia, said.
 
To date, numerous trials have been designed to shock and kill the virus. Those trials have confirmed just how difficult that task is and also prompted the strategy to incorporate research that uses diverse ways to respond to challenges in targeting the HIV reservoir:

• “Poke and clear” (previously “shock and kill”) involves drugs called latency-reversing agents (LRAs) to awaken the dormant virus in HIV-infected cells. Following activation, the virus-producing cells are eliminated by a second intervention.
• “Block and lock” is a strategy on the opposite side of the spectrum that, instead of awakening the HIV reservoir, drives the reservoir into a deeper permanent resting state.
• “Reduce and control” attempts to reduce the size of the reservoir and help the immune system control viral replication without the need for long-term ART.

These approaches may use one or more agents, including broadly neutralizing antibodies (bNAbs), various killer cells, therapeutic vaccines, and cell and gene therapies.

Beyond the science, the journey to an HIV cure will also require:

• Coordinating investments to pursue the most promising HIV cure research approaches
• Strengthening international collaborations to ensure a multidisciplinary approach for the development of a cure that is accessible and scalable in diverse settings
• Promoting the involvement of early-career researchers and researchers from countries most affected by HIV
• Supporting communication and information exchange between public and private sector researchers working on HIV cure research to alleviate the regulatory and logistical challenges associated with drug development
• Building HIV cure research capacity among different populations and settings to generate increased HIV cure research and advocacy globally
• Enhancing community engagement in HIV cure research through knowledge dissemination and capacity building for advocacy and effective engagement to represent their interests
• Boosting research on the psychosocial and ethical implications of participating in HIV cure clinical research to ensure that both participants and clinical trial designers are well-informed and prepared.

Key research goals for the next five years:  

• Understanding HIV reservoirs
• HIV reservoir measurement
• Mechanisms of virus control
• Targeting the provirus
• Targeting the immune system
• Cell and gene therapy
• Paediatric remission and cure
• Social, behavioural and ethical aspects of cure

About IAS – the International AIDS Society
IAS – the International AIDS Society – leads collective action on every front of the global HIV response through its membership base, scientific authority and convening power. Founded in 1988, the IAS is the world’s largest association of HIV professionals, with members in more than 170 countries. Working with its members, the IAS advocates and drives urgent action to reduce the impact of HIV. The IAS is also the steward of the world’s most prestigious HIV conferences: the International AIDS Conference, the IAS Conference on HIV Science, and the HIV Research for Prevention Conference.
For more information, visit www.iasociety.org.

About the IAS Towards an HIV Cure Programme 
Established in 2010, the IAS Towards an HIV Cure programme drives concerted efforts to accelerate global scientific research and engagement towards a cure for HIV. Particular focus is given to advancing the HIV cure field in settings where resources for HIV cure research are limited and facilitating interaction with HIV and other biomedical research areas.

About the International AIDS Conference 
The International AIDS Conference is the largest gathering on HIV and AIDS in the world. First convened during the peak of the AIDS epidemic in 1985, it continues to provide a unique forum for the intersection of science, advocacy and human rights. Each conference is an opportunity to strengthen policies and programmes that ensure an evidence-based response to the epidemic. The conference also serves as a focal point to intensify political and financial commitments to HIV and related epidemics. AIDS 2022, the 24th International AIDS Conference, will be held in Montreal, Canada, and virtually from 29 July to 2 August 2022.
For more information, visit www.aids2022.org.