Hopes for an HIV cure: familiar faces talking about a new goal

A panel of speakers discussed HIV Cure Research at a Town Hall Forum in San Francisco

Last night CIRM was one of the sponsors of a Town Forum on HIV Cure Research, along with the Gladstone Institutes and the AIDS Research Institute at UCSF. The panel of speakers included several who I’ve known since long before the word “cure” was even a realistic goal for HIV/AIDS.

Most the speakers and several of their colleagues in the audience first came into my world 27 years ago. My husband had just started as a clinician at San Francisco General’s Ward 86, one of the “ground zero” clinics where AIDS was exploding. For clinicians there at that time, care was mostly palliative with some attempt to prevent opportunistic infections that were killing so many of their patients.

Those times were often bleak. We lived on the hill above The General and our back deck was often the decompression zone for exhausted and pessimistic caregivers. I did cook for them a lot, but I must admit my most important kitchen tool was a corkscrew. I can’t recount the number of times I heard one of them say, “I wish we could find the cure and put ourselves out of work.” But hope of that was rarely heard.

My husband was the clinical trial coordinator for the San Francisco portion of the trial that got the first ever drug for AIDS, AZT, approved. When he would see patients at a private doctor’s office and not be able to get back to the lab in time, we often had blood samples in the fridge overnight. After AZT got approved, patients and providers alike had a love/hate relationship with the drug. Yes, it did improve symptoms for many patients, but it also caused severe side effects in some, and it was very difficult to tell which side of that risk-benefit scale your patient would be on.

Over the next few years, researchers developed and clinicians tested many combinations of drugs with marginal improvements. But the real breakthrough took nine years after AZT’s approval. In 1996 the protease inhibitors changed the face of the epidemic. In combination with older drugs clinicians could now keep the virus in check so HIV/AIDS became a chronic disease, not a rapidly progressing deadly one. The combination therapy did not, however, wipe out the virus.

Although initially elated, both the provider and patient communities again over time developed a love/hate relationship with the new meds. They were cumbersome, extremely costly and not free of side effects.

During last night’s event, Mike McCune, a speaker from the University of California, San Francisco, described how the field of HIV cure research moved beyond these revolutionary but still imperfect combination therapies to where it is now. He told how in 2008 AIDS activist Martin Delaney told a group of leaders that they had to collaborate across institutions and across disciplines if they were going to find a cure. (This same philosophy of the power of collaboration can be seen in the projects we fund using stem cells for HIV/AIDS.)

The federal government began funding three multi-institution collaborations as a result of Delaney’s advocacy. Those groups focused their efforts on two approaches, both dealing with the same problem: Once HIV infects a person, it creates latent, or quiet, reservoirs of virus that don’t circulate and don’t come in contact with drugs designed to kill it. These are the same two approaches that our speakers last night discussed as possible future cures:

• Directly destroy the reservoir
• Shock the virus out into the open where it can be killed.

Two speakers at last night’s event, UCSF’s McCune and Warner Greene of the Gladstone Institutes, discussed their ongoing efforts with latter approach, which they dubbed “shock and kill.” To be successful it will require a multi-drug regimen, one or more drugs to shock the virus out of hiding and one or more drugs to kill it. They are getting some positive results with early candidate drugs, but they likened them to AZT. As stand alones they will likely underwhelm, but they are a great first step to getting the right combinations that can finally evict the virus from patients once and for all.

Two other speakers, Louis Breton from the CIRM-funded company Calimmune and Hans-Peter Kiem from Seattle’s Fred Hutchison Cancer center, discussed the first approach. They want to eliminate the virus reservoir with the type of chemotherapy given to cancer patients prior to bone marrow transplant. These drugs destroy the blood-forming stem cells housed in the bone marrow that create all cells of the immune system. They then plan to give the patients their own blood-forming stem cells that have been genetically modified so they are resistant to HIV infection (here’s a description of this approach to treating HIV/AIDS) These cells will rebuild the patient’s blood and immune system with one that is resistant to HIV.

Calimune began a clinical trial with the technique this summer. You can read our press release on the innovative stem cell treatment. Kiem plans to start a trail soon as well.

All the speakers offered multiple cautions that this work is going to take years to perfect, and even more years to get to an affordable therapy that can cure AIDS in Africa where it is most urgent. But the group also radiated a collective optimism that was laid out by the opening speaker, Steve Deeks, also of UCSF. He described around 20 HIV-infected people world-wide who have been cleared of the disease through a variety of different approaches; one got a bone marrow transplant from a donor who was naturally resistant to HIV; some were started on intense anti-viral therapy early after infection: others got bone marrow transplants from donors that resulted in an immune response that seemed to wipe at the viral reservoir. Regardless of the method they show that cure is possible. The goal now is to scale those successes up and make them accessible to everyone.

Despite the hurdles ahead, the words of hope last night were hugely encouraging to the hundred or so attendees, and markedly different from what I was hearing on my deck above The General all those years ago.

Don Gibbons

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