Small study shows one-time cell therapy can control HIV infection

Re-engineering an HIV patient's own immune cells to find and destroy the virus succeeded in controlling the infection in a small first-in-human study, but researchers said work is needed to confirm the findings and determine which patients are most likely to benefit.

The Phase 1 trial involved CAR-T, a one-time therapy in which a patient's T-cells are extracted, altered and multiplied in a lab and infused back into their body. In this case, the CAR-T targeted the CD4 and CCR5 binding sites of the HIV.

If left untreated, the virus replicates and destroys infection-fighting cells, eventually progressing to Acquired Immunodeficiency Syndrome, or AIDS. Globally, around 41 million people are living with HIV, and while advancements in antiretroviral therapy have transformed the infection into a manageable condition, treatment must be continued for life.

Unlike previous HIV "cures" involving cancer patients given bone marrow stem cells from a donor with a rare genetic mutation that resists HIV infection, researchers said CAR-T could be used by a much broader patient population.

"Our goal is to make these therapies affordable and accessible," said Dr. Boro Dropulić, executive director of non-profit Caring Cross, which collaborated on the study with researchers at University of California, San Francisco, University of California, Davis and Case Western Reserve University Hospital.

Of three trial patients treated with a standard CAR-T dose, researchers said two maintained undetectable to very low levels of HIV after stopping antiretroviral therapy - one for over two years so far and another for nearly a year. A third participant had an early rebound but then controlled HIV to low but detectable levels.

Three other patients in the trial, which was focused on safety, were not pretreated with chemotherapy used to prepare the bone marrow for reinfusion of the cells, while another three were given a lower CAR-T dose.

"The two that have been off (HIV drugs) the longest and doing well were importantly diagnosed pretty quickly and put on therapy pretty quickly," said Dr. Steven Deeks, professor of medicine at the University of California, San Francisco and the study's lead investigator.

Antiretroviral therapy "freezes the virus in place" so that it can't mutate, while also preventing the body's immune system from getting "ravished by HIV," he explained.

Deeks said work is underway now to determine why some patients have responded well.

"The CAR-T cells disappeared after several weeks... so we're really trying to come up with a mechanism to explain that," he said.

Currently, CAR-T treatments are available for several types of blood cancer, and are being developed for autoimmune diseases like lupus and scleroderma.

"In the cancer settings, the overall burden of disease is much higher. Typically the CAR-T cells persist much longer," Deeks said.

He said patients in the HIV trial did not have the same kind of harsh side effects, including a severe inflammatory response known as cytokine release syndrome, that can occur in cancer patients treated with CAR-Ts.

The study findings were due to be presented in Boston on Tuesday at the annual meeting of the American Society of Cell and Gene Therapy.

-Reporting By Deena Beasley in Los Angeles; Editing by Bill Berkrot/Reuters