World AIDS Day: IAS launches new global scientific research strategy to cure HIV

Researchers Continue to Track Science Towards Workable Cure Amid Breakthrough Cases Like Patient Esperanza

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

The third edition of the IAS strategy comes shortly after it was announced that an Argentinian woman, known as “Patient Esperanza”, had been cured of HIV through natural immunity. This breakthrough provided new hope for a cure for HIV.

Timothy Ray Brown’s HIV Cure, also known as the ‘Berlin Patient’, in 2008 inspired IAS to set up the Towards a Cure for HIV program, founded by the Co-Discovery of HIV and winner of the Nobel Prize Françoise Barré-Sinoussi, in 2010. The objective is to lead concerted efforts to accelerate global scientific research and the commitment to a cure for HIV.

At AIDS 2012, the 19th edition AIDS Conference, in Washington DC, the IAS launched the first Towards a cure for HIV: a global science strategy, which has made healing 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”) healed via a stem cell transplant and two women apparently healed thanks to the natural immunity. In addition, several interventions have shown great promise for a cure in animal models of HIV.

“It is clear that a cure for HIV is achievable. The last five years of following science have taught us that ”, Adeeba kamarulzaman, Chairman of IAS and Director of the Center of Excellence for AIDS Research at the University of Malaysia in Malaysia, said.

“The recent case of Esperanza’s cured 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 often the elimination of all intact viruses occurs in elite controllers and what is the mechanism that makes this possible. We can then determine how we can replicate it on a large scale. We need an HIV cure that works for everyone so that we can end the HIV pandemic.

“The emergence of the Omicron SARS-CoV-2 variant reminds us all that vaccine inequity and our failure to end infectious diseases, such as HIV and tuberculosis, are on the same side of the coin – a devaluation of human life in the poor of countries. ”

An international scientific working group of the IAS, composed of 68 members, has developed the 2021 one-year strategy. The strategy reflects progress made, identifies gaps in the research agenda, and presents recommendations for HIV cure research over the next five years.

What we have learned:

  • Several cases of remission and eradication have been recorded. Research towards a cure for HIV is focusing on these people, as well as on HIV controllers, to better understand how a cure might work and to help identify targets for interventions related to HIV cure.
  • Research on HIV controllers has provided new information and new directions in the search for cures.
  • HIV reservoirs (cells that cause HIV after antiretroviral therapy or ART are stopped) are now seen as evolving rather than static sources of HIV unaffected by ART. Important differences among people living with HIV have been identified, such as biological sex, which affect the location and dynamics of the reservoir.
  • Technological developments provide a better understanding of how the latency of HIV is established and how the virus is reactivated after an interruption of analytical treatment (carried out as part of research into the cure of HIV). This makes it possible to identify new targets for HIV treatments.
  • New drugs and interventions are under development and have started to show positive results in animal models (preclinical).

The key to a cure: the HIV reservoir

“Over the past decade, research into a cure for HIV has intensified dramatically, but it remains clear that we will not cure HIV until we have a better understanding of where and how the virus is hiding and will be no better able to measure the reservoir of HIV. Sharon lewin, co-chair of the IAS Towards an HIV Cure program,
The president-elect of the IAS and director of the Peter Doherty Institute for Infection and Immunity in Australia, said.

To date, many tests have been designed to shock and kill the virus. These trials confirmed how difficult this task is and also prompted the strategy to integrate research using various ways to address the challenges of targeting the HIV reservoir:

  • “Poke and clear” (formerly “shock and kill”) involves drugs called latency reversing agents (LRAs) to wake up the virus dormant in HIV-infected cells. After activation, the virus-producing cells are eliminated by a second intervention.
  • “Block and lock” is an opposite-spectrum strategy that, instead of arousing the reservoir of HIV, drags the reservoir into a deeper permanent state of rest.
  • “Shrink 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 can use one or more agents, including broadly neutralizing antibodies (bNAb), various killer cells, therapeutic vaccines, and cell and gene therapies.

Beyond science, the cure for HIV will also require:

  • Coordinate investments to pursue the most promising HIV cure research approaches
  • Strengthening international collaborations to ensure a multidisciplinary approach for the development of an accessible and scalable remedy in various contexts
  • Promote the participation of early-career researchers and researchers from countries most affected by HIV
  • Support communication and information exchange between public and private sector researchers working on HIV cure research to alleviate regulatory and logistical challenges associated with drug development
  • Strengthen HIV cure research capacities among different populations and contexts to generate increased research and advocacy on HIV cures globally
  • Improve community engagement in HIV cure research through knowledge dissemination and capacity building for advocacy and effective engagement to represent their interests
  • Stimulate research on the psychosocial and ethical implications of participating in clinical research on HIV cure to ensure that participants and clinical trial designers are well informed and prepared.

Main research objectives for the next five years:

  • Understanding HIV reservoirs
  • HIV reservoir measurement
  • Virus control mechanisms
  • Target the provirus
  • Targeting the immune system
  • Cell and gene therapy
  • Pediatric remission and cure
  • Social, behavioral and ethical aspects of healing

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