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Top 10 HIV Clinical Developments of 2012

December 2012

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The Cure Agenda

A review of:

Steven Deeks, et al. Towards an HIV cure: a global scientific strategy. Nat Rev Immunol. 2012 Jul 20;12(8):607-14.

Nancie M. Archin, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 2012 Jul 26; 487:482.

There is an intensive effort to develop feasible strategies to eradicate HIV from latently infected cells, which could leading to a "functional," "complete" or "sterilizing" cure. Much of this work may not be apparent to the busy clinician still trying to figure out how to get a patient to take their once-a-day, single-tablet antiretroviral. But progress is being made -- so much so that a cure has moved from being a topic of speculation to a major item on the HIV scientific agenda.

Success in this area has been incremental, as tools are developed and standardized to better measure the effects of interventions. However, this year we saw a push forward, with a small study demonstrating the effects of an inhibitor of histone deacetylase (HDAC) on expression of virus in latently infected cells. HDACs serve to suppress expression of virus, and their inhibition can disrupt latency.

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The study, conducted by my University of North Carolina colleague David Margolis and his team looked at the HDAC inhibitor vorinostat, which has been used to treat malignancies. To examine the effects of the drug in vivo, the team first harvested resting CD4+ cells from 16 HIV-infected patients with suppressed viremia and exposed them to vorinostat. In 11 of the cell samples, HIV expression was induced with vorinostat exposure; eight of these patients were selected to receive the drug. After a single dose of vorinostat, each of these eight individuals had an detectable increase in HIV expression in their resting CD4 cells without an increase in HIV RNA levels in the blood.

This proof-of-concept study is important, as it shows that the theoretical effects of HDAC inhibition are real in actual people living with HIV. Extended doses of the drug are planned, and other agents that may carry less risk of toxicity are being studied by other groups. Overall, though, the clinical findings provide a shot in the arm for the cure effort. A group of international investigators produced their own cure manifesto, outlining where they see the field moving and what needs to be done to pave the way.

Many challenges remain before we start dialing up our patients to come in and get the cure. However, we are closer today than we were a year ago. The success we saw this year and the remarkable example of the "Berlin patient," who is experiencing a functional cure of his HIV following a bone marrow transplant from a donor who was homozygous for the CCR5 delta 32 deletion, buoy this effort and our hopes.

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Reader Comments:

Comment by: Ashley (QMsiijnYJx) Thu., Jan. 10, 2013 at 10:18 am EST
the HIV virus is very fragile once it is oudtsie of the human body. when it is exposed to the air, it dies in about 2 hours. so, dried semen will only have dead HIV cells. you are safe.
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Comment by: Mani (UubwaSyASLWZnBAlN) Thu., Jan. 10, 2013 at 9:29 am EST
I've talked to both my patrens about it at differnt times. My mom thinks it nessasary. She knows that teens r going to have sex and they need to be educated.My dad thinks its better to be educated then to not know anythingI think sex-ed is needed for everyone. I never though my dad (the republican who was in the army) Would be so libral
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Comment by: harleymc Tue., Dec. 25, 2012 at 11:02 pm EST
I was very happy to read this article.
I'm someone who's been on combinations containing boosted PIs and suffer badly with them. When my current script runs out in a few days I'll be switching to TDF/FTC/rilpivirine + raltegravir (already on the raltegravir). It was reassurring to read of an improvement in outcomes.

It's one thing to have a fabulous viral load but when side effects are both vile and life threatening, a change sounds brilliant.
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Comment by: Anonymous Mon., Dec. 17, 2012 at 10:48 am EST
good message of hope
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Comment by: Sean (Dublin, Ireland) Fri., Dec. 14, 2012 at 6:38 am EST
Thanks for the section called "The Cure Agenda". If YOU are feeling optimistic, that makes me feel optimistic.

Happy Yule!
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Comment by: Patrick D (South Deerfield, MA) Thu., Dec. 13, 2012 at 3:56 pm EST
Dr. Wohl writes "In the past, I have played with the HIV therapies of patients doing well, and on more than a few occasions I have been burned," then describes some of the benefits that may come from switching from a more complex drug regime to a more simplified one. Dr. Wohl clearly has his patients best interests in mind, but I want to remind him that when a switch in meds fails (temporarily or permanently) for patients who had been doing well on an older regime, it isn't the doctor who gets burned, it's the patient. I have had occasion to remind my own doctors of this, when they seem to want to fiddle with a regime that is working perfectly well, with negligible side effects, for no other reason than to put their signature on my treatment.

It can indeed be a benefit to simplify a drug regime, especially for patients who have trouble taking their meds in the first place. But as I've reminded several doctors, for many HIV patients, HIV drugs are not the only drugs we're taking (and that's not taking supplements into account), so simplifying the HIV drug regime alone doesn't result in not taking other drugs at other times of the day, and thus may not be a strong reason for changing a regime that's working.
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