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HXTC Therapy Safe, Well Tolerated in HIV Patients

HIV-specific ex-vivo expanded T cell therapy appears to be safe and well tolerated in people with HIV taking antiretroviral therapy who are virally suppressed.

HIV-specific ex-vivo expanded T cell (HXTC) therapy appears to be safe and well tolerated in people with HIV taking antiretroviral therapy (ART) who are virally suppressed, according to a new study published online September 21 in the journal Molecular Therapy.

“The safety and tolerability in this first proof-of-concept study for HXTC therapy is consistent with results of previous clinical trials of adoptively transferred virus-specific T cells, with most studies documenting only grade 1 or 2 adverse events,” investigators from the University of North Carolina (UNC) at Chapel Hill write.

Although ART has dramatically improved the treatment landscape for patients with HIV, it is not a cure. Indeed, the latent HIV that persists despite ART is known as the HIV reservoir and is the main obstacle to achieving an HIV cure.

In patients who have received ART, the existing HIV-specific immune response is insufficient to clear persistent HIV infection. However, adoptive T cell therapy represents one way to use the patient’s own immune response to fight HIV.

This therapeutic strategy has proven to be successful in treating virus-related cancers and infections after hematopoietic stem cell transplantation. Its approach involves collecting immune cells from the patient, expanding them in the laboratory by growing them to numbers in the billions range, and then returning them to the patient to help kill the cancer cells.

“We found that this approach of reeducation [of] the immune cells and reinfusing them was safe, which was the primary goal of the study,” senior author of the study, David Margolis, MD, Sarah Graham Kenan Distinguished Professor of Medicine and director of the UNC HIV Cure Center at the Institute of Global Health & Infectious Diseases, told Contagion®.

“This paves the way for the next step, which is to combine this immunotherapy approach with what is called 'latency reversal' therapy, in order to wake up the HIV out of its latent state where it is invisible to the immune system, then clear it out with the immunotherapy,” he added. “We hope a general audience will take away that this is a promising advancement for the field, but caution against overinterpreting the results on efficacy.”

The team as previously adapted this technique in the HIV setting, to expand broadly-specific cytotoxic T cells that simultaneously target multiple HIV antigens. Their new phase 1 proof-of-concept study focused on producing HXTCs, with the long-term goal of using them in strategies to clear persistent HIV infection.

In the study, the investigators gave 2 infusions of HXTCs over a 2-week period to 6 HIV-infected participants who were virally-suppressed on ART.

HXTC infusion was safe and well tolerated, according to the authors. Only 2 participants experienced transient, self-limiting fevers and myalgia of grade 1 severity. And 1 participant experienced a transient increase in viremia that resolved without intervention within 60 days. All other adverse events were not considered infusion-related.

The infusions led to a mild-to-moderate increase in T cell-mediated antiviral activity in 2 patients, although the authors note that the clinical significance of this is unknown.

Although an aggregate analysis showed no overall enhancement of the HIV-specific immune response, the investigators did not find this surprising; this is because the 2 infusions had comprised a relatively low dose of cells, they explain, and also because of a lack of in vivo stimuli to encourage expansion of the T cells when they were returned to the body.

Additionally, the investigators found no decrease in the size of the latent reservoir. However, this was most likely because of the absence of therapies that would disturb the latent reservoir and allow infected cells to be recognized land targeted by the immune response, they write.

“A critical question will be whether HXTC therapy in combination with latency-reversing agents can deplete the HIV reservoir to an extent that is measurable by current gold standard assays of HIV latency,” the authors conclude.

A study of HXTC used in combination with vorinostat is currently being evaluated in an ongoing clinical trial.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.