Two more HIV-1 patients kind of sort of cured-ish maybe

Many ERV readers are aware of 'The Berlin Patient'-- The fellow who has seemingly cleared the HIV-1 virus after receiving a bone marrow transplant to treat his lymphoma (we say 'seemingly' because we dont really know what 'cured' is with HIV yet).

The Berlin Patient was a rather unique case  in that he got a transplant from someone who is CCR5 negative.  CCR5 is the dominant co-receptor HIV-1 uses to infect host cells.  The idea was, if most of the patients HIV-susceptible cells were killed with radiation/chemo, and they were replaced with donor cells that lacked CCR5, then any virus remaining in the patient would have nowhere to go, and the patient would be, essentially, 'cured'.

And he is, essentially.

There are many problems with this approach as a 'cure' for HIV/AIDS, however.  The first hurdle is that the patient has to be dying from leukemia/lymphoma.  No physician would do a bone marrow transplant on someone for HIV/AIDS only.  The second hurdle is that in addition to finding a proper immunological 'match' for donation, that donor must also be CCR5 negative.  Very few people, usually of a similar genetic descent, thus similar MHC type, are CCR5 negative, which would leave swaths of individuals who might have HIV and blood cancers, but you could not find them a proper 'match' who was CCR5 negative.

Apparently, some physicians have tried something that has addressed that second point--

According to some media reports last night, two more HIV-1 patients have been cured-ish in a manner similar-ish to the Berlin Patient.  Kind of.  Maybe.

These two patients developed lymphomas that required treatment.  But they got regular ol bone marrow transplants from regular donors.  NOT CCR5 negative donors.  Im assuming that under 'normal' circumstances, antiretroviral treatment is stopped during cancer treatment.  Both protocols are rough on the patient, and you worry about the one that is going to kill them first, first-- the cancer.

These two patients physicians had them stay on antiretrovirals over the course of their chemo/radiation/treatment.  The idea being that the radiation/chemo would kill most of the infected cells, antiretrovirals would inhibit viral release from the remaining reservoirs, and the donor cells-- fresh, healthy, and a little pissed off immune cells-- would clean up whatever was left over.

It looks like this protocol worked.

One patient has had no detectable virus or antibodies to the virus for two years so far, the other three and a half years.

Now, I know as much about what happened here as you do from reading media reports.  This has not been published in a journal-- only reported at a conference yesterday.  There might be lots of caveats to this procedure.  Maybe these cancers were caught very early, and could be treated with a simpler/shorter regimen.  Maybe these patients were controlling HIV very well to begin with, low fitness virus, low viral loads, maybe even without antiretrovirals, and the radiation/chemo was enough to drive the virus to extinction in them, but it wouldnt work in someone infected with a more aggressive variant (one of the media reports that one of the patients has been infected since the 1980s-- the beginning of the epidemic. if he is still around, it does make me think that he was infected with a low-fitness variant).  Both of the patients were themselves CCR5 negative, so again, the virus in them was 'different'.

This might be GREAT news for some patients, and a functionally useless development for most.  But no doubt about it, its pretty damn awesome for at least two people.

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Somebody spoon feed me a possible mechanism for why the two new patients originally being CCR5 negative might be important. Or if you think it is irrelevant.
Neither of the linked-to reports is clear about the patient's original genotypes. Like if it is really CCR5 delta-32 alleles exactly (or equivalent), or if it's some other thing (a beta-chemokine) and whether they are homozygous or het. I looked for other articles to try to get the story straight and you all know how that goes with the lay press: No clear details, much error and muddled thinking. What I heard on the radio in an interview made me sorta think one of the patients was saying he was heterozygous for delta-32 variant. My brief foray in the science literature makes me think being het is not good enough. That makes it pretty hard for me to attempt to explain.
I am not trying to pun around with this hetero/homo and hard stuff, but there may be a whopper in there somewhere.

Actually, I was kind of wondering how a CCR5 (-/-) would be HIV+? Did I misunderstand something?

By Joe Ballenger (not verified) on 27 Jul 2012 #permalink

They were both CCR5 (+/-), slides from the presentation are online here (webcast of the talk too): http://pag.aids2012.org/session.aspx?s=274

Predictably, a lot of the media stories have jumped the gun and stated they're cured but they're still on ART so no one knows yet.

By Richard Jefferys (not verified) on 27 Jul 2012 #permalink

First the so-called "HIV scientists" have to define a set of falsable criteria to declare HIV as "cleared".

There are thousands of HIV-antibody positives with undetectable viral load (called elite controllers) for years and "HIV scientists" claim they're carriers of the virus anyway.

By PutinReloaded (not verified) on 29 Jul 2012 #permalink

Also, there are regularly cases of formerly HIV-antibody positives that revert to negative, but "HIV scientists" rather than saying these patiens have cleared HIV they pretend they were falsely diagnosed!

It is impossible to falsify the theory HIV/AIDS when contrary evidence is brushe aside with speculations like these.

By PutinReloaded (not verified) on 29 Jul 2012 #permalink

Joe -
Someone homozygous for the CCR5-delta-32 mutation can still acquire HIV because not all HIV is CCR5-tropic. That is, they can still be infected with virus that uses a co-receptor OTHER than CCR5 to enter target cells (like CXCR4).
Before patients are given CCR5-blocking drugs like Selzentry (maraviroc), they have to take a tropism test to make sure that their virus is CCR5-tropic.