Researchers continue to follow the science towards a scalable cure amid breakthrough cases such as the Esperanza patient
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 past 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 and we also get much better at measuring the HIV reservoir,” 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 approachesStrengthening international collaborations to ensure a multidisciplinary approach for the development of a cure that is accessible and scalable in diverse settingsPromoting the involvement of early-career researchers and researchers from countries most affected by HIVSupporting 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 developmentBuilding HIV cure research capacity among different populations and settings to generate increased HIV cure research and advocacy globallyEnhancing community engagement in HIV cure research through knowledge dissemination and capacity building for advocacy and effective engagement to represent their interestsBoosting 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 reservoirsHIV reservoir measurementMechanisms of virus controlTargeting the provirusTargeting the immune systemCell and gene therapyPaediatric remission and cureSocial, behavioural and ethical aspects of cure