Our research activities are focused on identifying new therapeutic approaches to target HIV reservoirs and to reinforce immune responses against HIV, to achieve scalable sustained remission of HIV infection.
We develop a translational research strategy, combining basic and clinical research, to identify mechanisms of HIV control that may be relevant in vivo. On this regard, we gain invaluable knowledge from unique cases of natural and post-treatment HIV control of infection and non-human primate models of SIV infection. We have identified cellular factors that condition the establishment and persistence of HIV infection in target cells and the characteristics of innate and adaptive immune responses that are associated with viral control in the absence of antiretroviral treatment. Our recent results have exposed key links between immunometabolism and HIV infection. In particular, we have shown that the metabolic status of CD4+ T cells determines their susceptibility to infection and we have proposed that this might be exploited to selectively eliminate infected cells. Moreover, critical differences in the quality and efficiency of CD8+ T cells from natural HIV controllers and HIV non-controllers are linked to their metabolic program. These results indicated that interventions altering immunometabolism could constitute an integrated approach to control HIV without ART.
Our new laboratory will expand our work on the identification of new potential ways to selectively eliminate HIV infected cells and to enhance immune responses to mimic those found in natural and post-treatment controllers. Based on the original concepts already generated, we are implementing pilot pre-clinical and clinical studies seeking HIV remission in people leaving with HIV. The protective mechanisms and the therapeutic strategies that we are exploring have the potential to be extrapolated to other infectious diseases.
A total of seven individuals worldwide (two patients in Berlin and patients in London, Düsseldorf, New York, City of Hope and Geneva) are considered likely to have been cured or to be in long-term remission of HIV infection after receiving a bone marrow transplant to treat blood cancer. Romuald, the Geneva patient, who is being monitored at Geneva University Hospitals (HUG), is the only one to have experienced HIV remission following a bone marrow transplant without the CCR5-delta 32 mutation. This rare genetic mutation is known to make CD4 cells naturally resistant to HIV.
The case published in Nature Medicine was part of a study coordinated by Professor Alexandra Calmy, MD, PhD, Director of the HIV/AIDS Unit in the Division of Infectious Diseases at Geneva University Hospitals (HUG) and Vice-Dean in the Faculty of Medicine at the University of Geneva (UNIGE), and Professor Asier Sáez-Cirión, Head of the Viral Reservoirs and Immune Control Unit at the Institut Pasteur (Paris), in collaboration with the Institut Cochin and the IciStem consortium.
Unlike in previous cases, where the presence of the CCR5-delta 32 mutation seems to have played a decisive role in the HIV outcome, the study published shows that the Geneva patient’s cells remain susceptible to HIV infection. Despite this, the virus remains undetectable in the patient nearly three years after antiretroviral treatment was stopped.
People living with HIV need to take antiretroviral treatment for life to prevent the virus from multiplying in their body. But some people, known as “post-treatment controllers,” have been able to discontinue their treatment while maintaining an undetectable viral load for several years. Starting treatment early could promote long-term control of the virus if treatment is discontinued. Scientists from the Institut Pasteur, the CEA, Inserm, Université Paris Cité and Université Paris-Saclay, in collaboration with Institut Cochin and with the support of MSDAvenir and ANRS Emerging Infectious Diseases, used an animal model to identify a window of opportunity for the introduction of treatment that promotes remission of HIV infection: it appears that starting treatment four weeks after infection promotes long-term control of the virus following the interruption of treatment after two years of antiretroviral therapy. These results highlight how important it is for people with HIV to be diagnosed and begin treatment as early as possible.
The findings were published in the journal Nature Communications on January 11, 2024.
Forty years after the discovery of HIV in 1983 at the Institut Pasteur, 38.4 million people were living with the virus worldwide in 2021.[Only two cases of people being cured had previously been described: the Berlin patient in 2009 and the London patient in 2019. The IciStem consortium now presents a new case of probable HIV cure, following a bone marrow transplant from a donor with the genetic mutation CCR5-delta 32, known to provide natural protection against HIV. The man, treated in Düsseldorf, received a stem cell transplant to treat leukemia, then was able to stop his antiretroviral treatment for HIV under supervision. Four years later, no trace of HIV virus can be detected in his body. This study offers further proof that it is possible to cure HIV and raises new therapeutic prospects for scientists and clinicians who have devoted their efforts to fighting the virus for the past 40 years. The findings are published on February 20 in Nature Medicine.
Current HIV treatments efficiently block viral multiplication but cannot cure infection as they do not target HIV infected cells. HIV cure or profound HIV remission have been described in three persons with HIV who underwent allogeneic stem cell transplantation to treat severe blood cancers. However, this procedure has not eradicated the virus in other persons. A work led by scientists from the University Medical Center Hamburg and Institut Pasteur in the context of the ICISTEM international consortium has analyzed the evolution of the immune system in 16 persons with HIV after allogeneic stem cell transplantation. The scientists identified a phase of strong activation of the immune system occurring after the transplant which may provide a window of vulnerability for the reseeding of the HIV reservoir in the expanding donor cells. Their findings are published in the journal Science Translational Medicine on May 6, 2020.
Cells from the rare individuals who naturally control HIV infection have been the focus of investigation for nearly 15 years with the aim of elucidating their specific features. Following research on the ANRS CO21 CODEX and CO6 PRIMO cohorts, scientists from the Institut Pasteur have described the characteristics of CD8 immune cells in these “HIV controller” subjects. The unique antiviral power of these immune cells can be attributed to an optimal metabolic program that confers persistence and the ability to react effectively against infected cells. Working ex vivo, the scientists successfully reprogrammed cells from infected non-controller individuals to give them the same antiviral potency as controllers’ cells. Their findings are published in the journal Nature Metabolism on July 12, 2019.
Current HIV treatments need to be taken for life by those infected as antiretroviral therapy is unable to eliminate viral reservoirs lurking in immune cells. Scientists have identified the characteristics of CD4 T lymphocytes that are preferentially infected by the virus. Thanks to metabolic activity inhibitors, the researchers have managed to destroy these infected cells, or ‘reservoirs’, ex vivo. Cell Metabolism, March 2019
Chez les personnes infectées par le VIH-2, la maladie ne progresse que rarement, même sans traitement. Il apparaît qu’elles disposent de ressources remarquables en lymphocytes CD8, particulièrement efficaces pour éliminer les cellules hébergeant le virus. Lire l’actualité complète sur le site de l’Inserm
A young woman now aged 18 and a half, who at birth was HIV-infected via mother-to-child transmission (during pregnancy or at delivery), is in virological remission, despite not having taken any antiretroviral therapy for the last 12 years. Monitored in the French ANRS pediatric cohort, this young woman seems to have benefited from the treatment that was initiated shortly after her birth and stopped approximately six years later. Her case suggests that long-term remission after early treatment is possible in children infected by HIV since birth, as demonstrated in adults in the ANRS VISCONTI study.
