Antiretroviral (ARV) therapy suppresses HIV, but viral replication rebounds once treatment is discontinued. The redistribution of lipids in the plasma membrane to form microdomains is crucial for viral entry and biogenesis during HIV infection. Researchers at Johns Hopkins University School of Medicine found neutral sphingomyelinase 2 (nSMase2) to be a key component of the late stages of HIV viral assembly and maturation; they hypothesized that nSMase2 inhibitors could help avoid viral rebound.

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).

Current antiretroviral therapies preserve the immune system, reduce HIV-associated morbidity and prevent HIV transmission but still, the virus persistence in CD4 cells remains a crucial factor to battle. Previous studies have explored the role of interleukin-2-inducible tyrosine kinase (ITK) inhibition in lymphoma, allergy and other infectious diseases.

In the larger picture, the fight against HIV has been a triumph of modern medicine. A patient diagnosed with HIV in the 1980s had a remaining life expectancy of 1 to 2 years. In 2023, they can expect to live another half century. But so far, an HIV vaccine has remained elusive. In the newest phase III failure, Janssen Pharmaceutical Cos. of Johnson and Johnson closed down its Mosaico trial more than a year ahead of schedule, following a data and safety monitoring board’s (DSMB) report saying the study was not expected to hit its primary endpoint.

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.

Fifteen years ago, at the 2008 Conference on Retroviruses and Opportunistic Infections (CROI), researchers announced that they had cured a patient – Timothy Ray Brown, initially known only as the Berlin Patient to preserve his privacy – of HIV through a hematopoietic stem cell transplant. Now, as researchers are gathered in Seattle for CROI 2023, reports of another cured patient were published Feb. 20, 2023, in Nature Medicine. Ten years after receiving a hematopoietic stem cell transplant, and 4 years after stopping antiretroviral treatment (ART), a 53-year-old patient may have been cured of HIV infection.