HIV and ID Observations

It’s right there, on page 1 of today’s Science Times:

Medical researchers are again in pursuit of a goal they had all but abandoned: curing AIDS.  Until recently, the possibility seemed little more than wishful thinking. But the experiences of two patients now suggest to many scientists that it may be achievable.

Two patients? What, did I miss something?

• Case One is the famous Berlin patient, Timothy Brown, who underwent a bone marrow transplant for leukemia from a CCR5-negative donor (homozygous for the delta-32 mutation). He’s been much discussed, much studied, and now much photographed. (Reminder: he’s really the second “Berlin Patient” — here’s the first — and he now lives in San Francisco; his interviews have been fascinating.)

  He’s a bona fide cure, with no evidence of HIV in blood by the most sensitive techniques or in various biopsies where the virus could potentially hide out (brain, bone marrow, rectal mucosa). Plus, his HIV antibody test is fading.To date, we don’t know what exactly led to his cure — if it was the ablation procedure that precedes the transplant, the CCR5-negative donor, the beneficial effects of graft-vs-host, or some combination of these factors.

  As I’ve mentioned before, we also don’t know why there hasn’t been another case yet, given that the cure was first reported in 2008 — seems likely that by now someone else with HIV would have required a bone marrow transplant and had the good fortune to have a CCR5-negative donor, though maybe that’s just the non-oncologist’s view (what do I know).

• Case Two? This case was reported at ICAAC in September, using the “zinc finger nuclease modification of CD4 cells” approach championed by Sangamo and first reported at CROI earlier this year.

  (Sangamo — it’s a biotech company, not a maker of 1980s video games.)

  The patient’s cells are removed from the body by pheresis, treated with the magic zinc finger nuclease which alters the surface CCR5 receptor on the CD4 cell, making these cells less susceptible to infection, then they are reinfused.

  We heard at CROI that such modified cells can engraft, and at ICAAC, researchers reported that one of the patients in a small clinical study (n=6) maintained (after a brief viral rebound) undetectable HIV RNA in the blood after stopping HIV treatment.An important detail — he was heterozygous for the delta-32 mutation, meaning that already he had partial resistance to HIV, and a greater likelihood of slow HIV progression.

  The reason this case is being viewed with such caution — and not trumpeted as a cure — is that the duration of follow-up has been only 12 weeks. The HIV literature includes other cases of “spontaneous” control of the virus (including the original Berlin patient!), most of which ultimately turned out to be transient. Experienced HIV clinicians probably have a few cases in their own practices who seemed to be on this exciting path back during the heyday of treatment interruption.

  In other words, these were not cures.

So in fact, nothing new here in the Times on the HIV cure scorecard. One cure, and one tantalizing case that was reported two months ago.

But what is new is the level of excitement surrounding the effort. Whether it’s something analogous to the zinc finger nuclease approach, or the use of drugs to stimulate and then eradicate the latent viral reservoir, or something completely novel being dreamt up by the field’s boldest thinkers (here’s my vote for one potential candidate), we can now say to our patients that a cure for HIV infection is potentially achievable in their lifetime.

And that’s a wonderful thing to say.