We all look different to HIV, a virus that destroys the immune system. The defensive cells record every interaction with foreign agents, infections from viruses and bacteria, but also with mechanisms occurring within the body, such as microbiome metabolism, the effects of aging, or the development of diseases. At a preconference session at the 13th IAS Conference on HIV Science (IAS 2025), scientists explained the interactions of different microorganisms with HIV.
While people living with HIV can lead virtually normal lives thanks to antiretroviral therapy (ART), HIV persists in a latent state within cellular reservoirs that scientists do not know how to eliminate. “Transcription is a critical step in the viral life cycle. … But there are currently no drugs suppressing HIV transcription, and that may be one of the reasons why current antiretroviral therapy is not curative,” Melanie Ott told the audience at the 13th IAS Conference on HIV Science this week in Kigali, Rwanda.
HIV infects immune cells, mainly CD4+ T cells. But they are not the only ones. It also settles in the genome of myeloid cells, monocytes or macrophages. According to a study from Johns Hopkins University, the viral DNA inserted into myeloid cells is functional. The virus also reactivated from the monocyte-derived macrophage reservoir. New cure strategies need to take these cells into account to eradicate the virus from the body.
HIV research is a winding road where one obstacle leads to another, slowing down success. The first barrier to getting the cure starts before one can even talk about it. “Cure may be too powerful and promising a term. Remission is probably better,” said John Mellors, whose work led to the universal use of plasma HIV-1 RNA and CD4+ T-cell counts in HIV-1 infection.
“Cure means maintaining an undetectable viral load off antiretroviral treatment. That means you cannot transmit it to people. Within that definition, there are people that have complete eradication of every single virus. And then, you have people that have a low level of virus that are able to keep under control without drugs,” Sharon Lewin told BioWorld. “Remission is maintaining a viral load less than 50 copies per milliliter in the absence of any retroviral. But there is still virus detectable,” she explained. Lewin is the director of The Peter Doherty Institute for Infection and Immunity in Melbourne, and the president of the International AIDS Society (IAS).
Anthony Fauci has retired from his position as director of the National Institute of Allergy and Infectious Diseases (NIAID) and as chief medical advisor to the U.S. president. But Fauci, who has advised every president since Ronald Reagan, continues to share his encyclopedic knowledge with the HIV research community, as he has since the beginning of the HIV pandemic. Fauci co-founded the first National Conference on Human Retroviruses and related infections in 1993. At the Opening Session of the 30th edition of the Conference on Retroviruses and Opportunistic Infections (CROI), he highlighted the advances that have collectively extended the life expectancy of newly diagnosed patients by decades.
Results published Feb. 17, 2023, in Immunity have given a wider view of what happens in the earliest stages of HIV infection. Treatments against HIV prevent the replication of the virus, but do not kill the reservoir of latently infected cells that starts to build almost immediately upon infection.
A multiomic analysis of the HIV reservoir has characterized the phenotypic and epigenetic heterogenicity of the virus-infected memory CD4+ T-cell population in people living with HIV taking antiretroviral therapy (ART-PLWH). This is the step towards an ex vivo single-cell atlas for these cells, which could help to design new strategies to eliminate the reservoir.
Researchers around the world are making advances in understanding how HIV becomes latent and seeking out vulnerabilities that could provide routes to targeting reservoirs and eliminating them.
Investigators from the Ragon Institute of MGH, MIT and Harvard have reported new details on a so-called exceptional elite controller, a patient who has rid herself of an HIV infection.
Like Berlin patient Timothy Ray Brown before him, London patient Adam Castillejo, whose case was top story of the 2019 Conference on Retroviruses and Opportunistic Infections (CROI), energized the HIV cure research field by his sheer existence. Curing HIV, Pablo Tebas told the audience at a themed discussion on curative strategies, “has been considered [for] a long time the holy grail.”
