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Juan Ambrosioni 1,2 and María Salgado1,3, 4

1- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain

2-HIV Unit, Infectious Disease Service, Hospital Clinic- FUNDACIÓ DE RECERCA CLÍNIC BARCELONA-IDIBAPS, University of Barcelona, Barcelona, Spain

3- IrsiCaixa AIDS Research Institute, Badalona, Spain

4-Germans Trias i Pujol Research Institute, Badalona, Spain


HIV infection is currently a chronic condition manageable with specific medications, known as antiretroviral therapy (ART). Modern ART is easy to take, orally or even injectable in some cases, and includes the combination of two or three drugs that, in general, are co-formulated to simplify administration.  Moreover, when persons with HIV are diagnosed soon after infection, and when ART is rapidly initiated, life expectancy becomes similar to that of the general population (Trickey et at, Lancet Heal Longev, 2022). Not less important is that, if somebody regularly takes the medication and has very low virus in the body and blood (below the detection level of current techniques) the virus cannot be transmitted to others even if condoms are not used. This fact has led to the concept and much publicized phrase: ‘U = U’ or ‘Undetectable = Untransmittable’. 


However, ART should be taken lifelong because the virus remains ‘deeply sleeping’ in the cells (the virus integrates into the body cells, forming what is known as the ‘Viral Reservoir’) producing a rapid viral rebound if ART is discontinued. This prolonged treatment may lead to chronic toxicities and represents a significant cost for health systems. In addition, HIV remains associated to what are called the ‘non-AIDS comorbidities’ (diseases such as cancers or cardiovascular complications) that appear earlier than in the general population even in people who are rigorous in taking ART (Prodel et al, J Public health Res, 2021). This is caused by an increased state of inflammation in the body for everybody with HIV, even when viremia is suppressed. Last but not least, people with HIV still experience stigma and discrimination in many settings (Ferguson L,  et al, J Int AIDS Soc, 2022).


For all the above mentioned reasons, a cure for HIV infection remains a very relevant issue. Only a few exceptional cases are considered as cured of HIV by observing no viral rebound after a medical intervention (Hütter G, et al, NEJM 2009;  Gupta RK, et al, Nature 2019; and Jensen, et al, Nat Med 2023). All these cases have in common the need for allogenic stem cell transplantation because were suffering from serious blood cancers where other less aggressive therapies have failed. However, this is a complex and aggressive therapy and cannot be considered for all the people with HIV in the world, which is nowadays close to 40 million. Cases of prolonged aviremia (no replication of the virus) after variable time on ART, and not receiving stem cell transplantation or similar therapies, have also been described. They are called pos-treatment controllers (they have received ART for some time) and are a more achievable model to reproduce on a larger scale (Sáez-Cirión A, et al, PLoS Pathog. 2013).

For many years, many different strategies to eliminate the reservoirs or to potentiate, modulate and stimulate the immune system have been under investigation, with the aim to reduce the latency and allow the control of the virus by the immune system of the organism, without the need of long-life ART (Deeks et al, Nature Med. 2021). Some of these strategies have reached a clinical stage, where ART needs to be stopped to evaluate if the treatment for HIV cure or prolonged aviremia has worked, in the frame of clinical trials. This interruption of the ART is known as ‘Analytical Treatment Interruption’, ATI). 

The implications for people with HIV who participate in this type of studies are sometimes underestimated by the investigations and deserve a deeper analysis to guarantee a success of the research and the engagement with the needs of the community. Some of these implications are related to the balance about expectations and participant feelings.  A recent study, has seen that managing expectations, focusing on participants' contributions, and providing support to reduce feelings of having failed the research team and/or the HIV community following viral rebound should be part of HIV cure trial design (Bilger, et al, HIV Res Clin Pract, 2023). That implies that discussing the mental health impact of rebound during consent, distinct from risk, is needed.

Another important implication of the trials including an ATI step is related with the risk of HIV viral rebound and eventually, the transmission of HIV to others. In this way, the last studies are proposing a partner protection package (P3) approach to address these concerns, what implies three basic considerations: (1) ensuring the scientific and social value of the ATI and the trial, (2) reducing the likelihood of unintended HIV transmission, and (3) ensuring prompt management of any acquired HIV infection (Dubé, et al, The Lancet ID, 2023). We need to outline possible ways of implementing these basic considerations, with special focus a women-based research that has been traditionally under-included in trials (Dubé, et al, HIV Res Clin Pract, 2023).

A good model of researchers-community collaborative work is the stablished within the Martin Dellaney Collaboratories, funded by the NAIDS-NIH. In these programs, a Community Advisory Board (CAB) is always connected with the different collaboratories to have a bidirectional communication between the researches and the HIV community.  That generates an important engagement of the different participants of the studies with a good follow up of the research outcomes and the knowledge of the significant contribution that have done to the progress of the science. In addition, the CAB shares important guidelines to disseminate the science using plain language or more respectful vocabulary. 

Thus, a deep reflection about the risks and potential advantages, and the way to protect other people must be considered by the participants of these studies, and the health-care professionals who assist them and lead them through different cure studies.

While a cure or a prolonged aviremia without ART are still far away for the majority of the 40 million people with HIV in the world, the awareness of how the research advances on these topics, the risks, the advantages and consequences of these interventions, is important for everybody. Without these brave volunteers who take part of these studies, science cannot progress, and all the scientific community and the population in general should acknowledge them. The cure for HIV is challenging for scientists in the lab, for clinicians seeing the persons with HIV and for the people with HIV themselves. But working all together, advances towards HIV cure will continue.

HIV Cure from the perspective of scientists and community
DOI 10.24175/sbd.2024.000005

George Cv: Nuestro equipo
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