Early trial shows promise for one‑shot cure for HIV 

/ California Institute for Regenerative Medicine (CIRM)

By Holly Alyssa MacCormick 

A single infusion of a modified CAR-T cell therapy could pave the way for a potential one-shot cure for HIV, according to preliminary findings of a small, early-stage clinical trial. Steven G. Deeks, MD, the principal investigator of this California Institute for Regenerative Medicine (CIRM)-funded clinical trial, discussed the findings at a recent CIRM board meeting. 

Steven Deeks, MD Photo: UCSF

Roughly 40 million people worldwide and more than 143,000 Californians have HIV. Currently, HIV is treated with antiretroviral therapies These drugs are effective and relatively affordable with the aid of health insurance.  

“The fundamental problem with [the existing] treatment is that it requires a person to be engaged in healthcare and stay engaged for their entire life,” said Deeks. 

For many people, that’s a major barrier. 

In his presentation, Deeks discussed the clinical trial of nine cisgender males with HIV. Preliminary results of this study suggest the therapy has the potential to control HIV for months. He also discussed possible directions for future studies, including increasing gender and ethnic diversity among participants and finding ways to make the strategy safer and more scalable. 

Why a new HIV treatment is needed 

Existing HIV therapies target cells actively producing HIV, but not cells with inactive “latent” HIV. So, these therapies must be taken indefinitely on a strict schedule—daily for the pill form, or every 1,2, or 6 months for the injectable form—or the HIV quickly rebounds.  

There are many reasons why a person with HIV may not be able to take or maintain anti-HIV drugs for life, such as side effects, stigma associated with taking these drugs, and the high cost of these therapies if a person loses health insurance or access to HIV programs. 

When people with HIV stop taking antiretroviral drugs, their virus rebounds, often dramatically, which is harmful. Also, when the virus rebounds, transmission to partners becomes possible. That’s why Deeks and other HIV experts are concerned about recent cuts to HIV funding programs, such as the State Department’s plan to end 23 years of support for the President’s Emergency Plan for AIDS Relief (PEPFAR) this September.  

PEPFAR supported life-saving anti-HIV drugs for more than 20.6M people in 55 countries, including 566,000 children with HIV, according to HIV.gov. 

“Globally, we are concerned that thousands and thousands, maybe many more people who’ve been on treatment, [will] go off treatment, [and HIV] is rebounding and progressing,” said Deeks.  

A single-dose treatment for HIV—like the one Deeks and his team are developing—could help solve the problem of needing continuous and uninterrupted therapy for HIV, but until recently, this seemed nearly impossible. 

CAR-T therapy for HIV 

CAR-T cell therapy is often associated with cancer treatment. However, researchers first developed it in the 1980s with the aim of treating HIV. Early efforts to use CAR-T cell therapy to treat HIV were unsuccessful, so this therapy was developed to treat cancer. But, in roughly the last decade, researchers have gained a better understanding of HIV and how to target its active and latent cell forms. 

In 2020, Deeks and his team began a clinical trial that uses a technique called CAR-T therapy. The goal was to “train” the patient’s own immune system to identify and destroy HIV infected cells. 

CAR-T therapy involves taking some of a patient’s T-cells from their body. Those cells are then modified with a genetically engineered molecule called a chimeric antigen receptor (CAR). Then the re-engineered T cells are injected back into the patient.  

In this clinical trial, the CAR-T therapy targets HIV infected cells for destruction by the patient’s own immune system. The treatment includes an additional feature to protect the CAR-T cells from getting infected with HIV themselves. 

Clinical trial process and preliminary results 

The study consisted of three groups of three participants. In one group, patients simply stopped taking anti-HIV drugs. Then they each received an injection of the CAR-T therapy that same day. Participants in that group had no detectable CAR-T cells in the blood. All three participants had a resurgence of HIV, indicating the therapy wasn’t sufficient on its own.  

The remaining six participants received a low dose of chemotherapy three days before stopping anti-HIV drugs. The chemotherapy slightly suppresses the patient’s immune system. This is so it doesn’t attack and destroy the genetically engineered cells.  

Three of these participants received a low dose of the CAR-T therapy. Three received a high dose of the CAR-T therapy. Of these six participants, two had undetectable to low viral loads of HIV. (One for nearly a year and the other for nearly two years.) A third patient had intermittent control of HIV for almost three months.   

This clinical trial is slated for completion in late December 2029.  

“A so-called one-shot cure [for HIV] is no longer aspirational,” said Deeks. “I think it’s feasible.”

Closer to Cures is a speaker series featuring presentations by CIRM-funded awardees at each meeting of the California Institute for Regenerative Medicine’s governing board. The board is known as the Independent Citizens Oversight Committee (ICOC). The meetings and this speaker series are open to the public and  livestreamed on YouTube. 

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