40 years after the discovery of HIV: research nurtures the hope of remission

« 40 years of HIV science »

For 40 years, since the virus was first identified at the Institut Pasteur, researchers have been working to describe HIV and understand the various stages of infection, right through to its integration into the host cell genome. This knowledge has contributed to numerous scientific and medical advances in curbing the infection, and has also enabled people living with HIV to live longer, with a better quality of life. The personalities gathered at the opening of the “40 years of HIV science” symposium share the observation that, despite major advances, the fight against HIV is not over, even if they have high hopes for finding the paths to remission and cure: “I salute these years of research, medical advances and activism, but many challenges remain. Despite this progress, 630,000 people died of AIDS in 2022¹ and new infections continue to occur. The fight against HIV is not over. This international fight continues, and no one will be left behind,” said Stewart Cole, Director General of Institut Pasteur.

Forty years after the discovery of HIV, basic research is still deciphering the mechanisms of infection

To meet these challenges, various fields of investigation are being actively explored, in particular to decipher the molecular mechanisms involved in HIV replication, as well as its integration into the host cell genome. Thanks to cutting-edge techniques, it has been surprisingly demonstrated that the virus targets cell nuclei. In this way, it takes advantage of all the host cell’s mechanisms to multiply its genome and reconstitute viral particles to infect other cells. This discovery of cell nucleus targeting opens up new avenues for combating viral replication and persistence. Another avenue being explored is innate immunity, i.e. the body’s own defences, which can be mobilized immediately to block the virus as soon as it enters the cell. It is therefore possible to stimulate this natural response by developing immunotherapy treatments.

Dislodging the virus from all the cells in the body where it is lodged is essential to prevent it from persisting. Scientists are using new technologies to determine the location of reservoirs and understand how the virus settles there, evading the immune system and antiretroviral treatments. The lymph nodes and intestines are among the reservoirs being closely scrutinized by researchers.

Analyze the natural ability of certain people to block the virus

How can we explain the fact that, without antiretroviral treatment, some people are able to block the virus by slowing its progression or preventing viral reservoirs from being reactivated? These people control HIV infection thanks to optimal immune responses that neutralize the virus. Succeeding in reproducing the particularities of the immune cells responsible for this optimal activity is one way of exploring new therapeutic solutions to overcome HIV infection.

“The identification of HIV control in certain individuals is helping to boost hopes of remission and cure, and offers us a unique opportunity to study the underlying mechanisms,” explains Asier Sáez-Cirión, head of the Viral Reservoirs and Immune Control Unit at the Institut Pasteur.

Researchers are also interested in people who, despite heavy exposure to HIV, have never been contaminated, thanks to a genetic mutation that prevents the virus from entering their cells. This mutation could be induced by gene therapy. Developing molecular scissors to render the organism resistant, or targeting the virus once it has been integrated into the cells to eliminate it, are all avenues being explored to achieve a long-term cure.

Using the social sciences to make therapeutic innovation accessible to all

The challenges of medical research to understand how HIV infection works are compounded by societal issues. For 40 years, patient associations, scientists and social science researchers have been working together to change the way society looks at HIV and AIDS, by combating discrimination and the stigmatization of people living with HIV, and by mobilizing public authorities to promote prevention and early diagnosis. The availability of rapid diagnostic tests is one of the concrete results of this collective mobilization. Therapeutic innovation alone is not enough; it must be accompanied by targeted, relevant programs to reach people at risk of HIV contamination. The community-based research that has developed in this fight against HIV aims to complement knowledge to reduce inequalities of access and adapt to patients’ situations. 9.2 million people living with HIV still have no access to antiretroviral treatment in 2022. Access to antiretroviral treatment and means of preventing infection, such as PrEP (pre-exposure prophylaxis), are also societal battles being fought by stakeholders in the fight against HIV.

To achieve the goal of eradication, the international community mobilized at this symposium confirmed that we need to redouble our efforts to explore all the scientific avenues that open up with each new discovery about the virus, and to improve prevention and access to therapies.

Last but not least, the expertise brought together over the past 40 years in HIV research has also contributed to the fight against other diseases, such as Covid recently.