Working Toward a Cure for HIV: Where Are We?

The landscape of HIV treatment continues to shift and grow, with new and streamlined therapies introduced on a regular basis. People living with HIV today can lead very different lives than those of people who were diagnosed in the ’90s and early 2000s. Antiretroviral therapy (ART) makes it possible for a person living with HIV to experience complete viral suppression, even engaging in condomless sexual intercourse, or gestating a baby without fear of passing on the virus (Undetectable=Untransmittable). Investigators, however, are still in pursuit of the holy grail—total eradication of HIV from the body. Is there a cure? How long until we find it? And will it work for the majority of people living with HIV?

It’s important to understand that the definition of “cure” differs from investigator to investigator, and some disdain the term altogether. “I don’t even use the word ‘cure’ anymore,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told Contagion®. “I refer to it as different pathways to a sustained remission.”

Although ART has been considered a gamechanger for people living with HIV, allowing them to be completely virally suppressed for long periods, it’s not the right option for certain patients. “People psychologically don’t like to be reminded every day that they have to take ART to suppress their virus,” Fauci said. “It reminds you every single day that you’ve got a virus and you have to do something to suppress it.” Complicating things is the fact that some patients are quite sensitive to the potentially toxic side effects of ART. Other patients are simply resistant to ART. The goal, he said, is to offer people something that lasts longer than a daily pill.

In March at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019), investigators revealed results from the FLAIR and ATLAS studies, which showed that monthly long-acting injections of cabotegravir and rilpivirine were non-inferior to oral ART for adults with virologically suppressed HIV-1 infections.

According to Fauci, another important development in recent clinical trials is the discovery that combinations of broadly neutralizing HIV-1 antibodies (bNAbs) given as infusions every few weeks to months can replace ART and induce a lengthy remission. “It is certainly not risky,” he said of this therapy. “We’ve done clinical trials on many, many people. The adverse event rate is low and they’re well-tolerated.” The trials are currently in phase 1, meaning this promising therapy is several years away from coming to the market.

Nevertheless, Fauci feels that implementing bNAbs as an HIV therapy is more realistic than gene editing and stem cell transplants, 2 other potential cures that are being discussed. The 2 patients who supposedly have been cured, known as the Berlin patient and the London patient, both received stem cell transplants for cancer that ended up also inducing long-term remission of their HIV.

However, as Fauci explains, editing a person’s genes or wiping out their entire immune system is not a trivial thing; the logistics of performing these kinds of procedures on a larger scale are daunting. “What [are these treatments] going to do for the 36 million people living with HIV?” he asked.

Another potential avenue toward a cure involves immune enhancements with chimeric antigen receptors, also known as CAR-T cells. Scott Kitchen, PhD, assistant professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, sees this is an area worth focusing on. Kitchen and his team have come up with a method of genetically modifying the immune system’s T cells with a vector based on HIV. The idea is that when the engineered T cells are put back into a patient’s body, the cells express a molecule that targets and kills HIV cells.

CAR-T therapy has had success in animal models, and the hope is it will offer a cure for humans as well. “The individual that has this treatment basically has this lifelong production of HIV-specific cells,” Kitchen told Contagion®. There’s even talk of one day being able to directly manipulate cells inside the body rather than in a test tube. However, Kitchen cautions that this “pie in the sky” idea likely won’t happen any time soon, if it happens at all. “It’s still very, very early,” he said of advances in this area.

Researchers are particularly interested in the strides that CAR-T cell therapy has made in treating cancer over the past couple of years. “If we learn how to develop and use CAR-T cells in cancer...the approach [with HIV] will be somewhat the same,” said Paul Volberding, MD, professor of medicine at the University of California, San Francisco. “Stay tuned and maybe even keep a close eye on cancer therapy.”

Like other HIV researchers, Volberding agrees that predictions of a complete cure are premature. “It’s not in sight yet, but there still is a lot of work going on,” he said, citing “cautious optimism” as the mood in the HIV community. “We’re definitely still cautious.”

Contagion^® publishes an annual update on the clinical community's progress on a cure for HIV. Read last year's update here.