Dammit. Transplant recipients not cured of HIV

Bone marrow transplants and HIV. I have been writing about this topic for a long time. Quick recap.

1. Some people with HIV-1 infection subsequently get blood cancers.

2. Sometimes those blood cancers need to be treated with bone marrow transplants.

2a. If the patient gets a transplant from a CCR5 negative donor, its great! HIV prefers to use CCR5 for a co-receptor, so if its not there, HIV has a bad time. Example: Berlin patient.

2b. If the patient gets a transplant from a regular immunological match, they are taken off of antiretrovirals during treatment. Treating the cancer is a priority, and the side-effects of antiretrovirals are too much during these procedures.

2c. If the patient gets a transplant from a regular immunological match... what if physicians keep them on antiretrovirals? If they can handle the side-effects, do the drugs help keep HIV in check, while radiation/chemo kill the infected cells, and the new donor cells kill the old cells?

There was some hope last year, and again earlier this year, that 2c works. A few patients stayed on drugs during their cancer treatment, and they were virus free for a long time. So their physicians took them off their anti-HIV drugs. And now the virus is back, in both patients:

Marrow Transplants Fail to Cure Two H.I.V. Patients

Two patients in Boston whom doctors hoped they had cured of both H.I.V. and cancer through bone-marrow transplants have seen their H.I.V. return, researchers said Friday.

Surprise. HIV does something extremely HIV-like. *sigh* Hopefully the patients will still respond well to their previous antiretrovirals. Taking them off meds allowed the virus to replicate and expand the quasispecies. They cannot go back to their original baseline-- the diversity in the quasispecies has raised the baseline. It would have been better to leave them on the drugs and keep the virus from replicating. But their physicians didnt. In fact, he knew it before he took the patients off the drugs:

“It could come back in a week, or in six months,” said Dr. Timothy Henrich, a doctor overseeing the two patients. “Only time will tell.”

And yet, he suggested they go off the drugs? What? WHY??


I dont know a nice way to put this. Dr. Timothy Henrich went to Yale and Harvard and works at Brigham and Womens Hospital. Those are not shit institutions (right?). I find it hard to imagine Henrich didnt understand basic quasispecies population dynamics and the implications of rebuilding that quasispecies in his patients. And yet, he took them off their meds. Look, I am, unquestionably, an evil scientist. My response to 'Why?' as to why I do/want to do things is frequently 'Because I can.' But taking these two patients off antiretrovirals was a damn stupid move. Unless these patients were being killed by their antiretrovirals (they were not), taking them off drugs was a gamble that could only favor Henrich. He would get to be 'The Guy Who Cured HIV!!!!'* The patients were 'HIV free' with or without the meds. If taking them off drugs was a losing bet, the only people who would have to live with those consequences are the two patients.



I feel the two patients in this study were wronged by Henrich, and whoever approved this line of research. Treating HIV+ bone marrow transplant recipients with antiretrovirals during cancer treatment was brilliant. Taking them off meds later was stupid.




* Once again, we are talking about this because of media reports. We are never talking about the real publication FIRST, we are talking about  press releases and interviews. This is a weird way to do science. Do not like it.

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I'm wondering how much input the patients themselves had in the decision to stop ARVs.How was the decision sold to them by their doctor? Where was the informed consent?

Late to the party but...

Yes, those are great institutions, but also ones that favor competition and risk taking.

Also, question about quasispecies and resistance that I don't recall if you've covered: With antibiotic resistance, the mutations that confer resistance often have selective disadvantages. Removing the antibiotic as a selective pressure (or switching to an antibiotic with different mechanism) will allow outgrowth of non-resistant bugs since they have a selective advantage. Does a similar thing happen with HIV (could you for instance cycle the drug cocktails used or is it always better to just use everything you can).