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MORE ON SCHIAVO: Whatever happened to theological moderation? My take in the Sunday Times.
SUPER-HIV: Since the mainstream media has been doing such a piss-poor job of understanding or even explaining the alleged case of super-HIV, with the New York Times leading the pack in reckless, dumb reporting, I thought it would be worth posting the technical details we now have. Some of this stuff is available online only to doctors subscribing to certain websites. One of them at NIH sent me this analysis:
The results of genotyping studies to ascertain the drug susceptibility of the patient’s HIV-1 revealed broad resistance to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors. The genotype was confirmed by further testing done at ViroLogic with one notable difference: the detection of a mixture of M184V/I in reverse transcriptase (RT). The researchers interpreted the collection of mutations to confer resistance to thymidine analogues, lamivudine and emtricitabine, reduced susceptibility to abacavir and tenofovir, high-level resistance to nevirapine, possibly an attenuated response to efavirenz, and broad resistance to protease inhibitors. They also noted low degrees of reduced susceptibility to lamivudine and emtricitabine. Superficially, these findings suggest little evidence of drug resistance to these agents. However, given the presence of mixtures of viral species detected at aminoacid positions 184, 210, and 215 in RT – all resistance-conferring substitutions for NRTI – a discordance between the genotype and phenotype results was predicted. Additionally, the results of the phenotyping assay showed the virus was highly resistant to nevirapine and all commercially available protease inhibitors. The virus tested sensitive to two NNRTI, efavirenz and delavirdine, and to enfurvitide, an inhibitor that blocks HIV-1 entry into cells.
Treatment options for the patient are therefore limited. His virus is resistant to all protease inhibitors and nevirapine, and is sensitive to efurvitide and efavirenz. The phenotype data for NRTI show susceptibility to various drugs in this class. However, viral mixtures with aminoacid substitutions at positions 184 (conferring resistance to lamivudine and emtricitabine) and with thymidine analogue mutations at 210 and 215 (conferring resistance to abacavir and thymidine analogues) suggests that most NRTIs are unlikely to be effective. Furthermore, the presence of M41L together with mixtures reflected at positions 210 and 219 in RT predicts an attenuated response to tenofovir. Therefore efurvitide and efavirenz are the only two antiretroviral drugs that can possibly provide full activity against the virus in this patient. As I understand it HAART has been initiated, including efurvitide and efavirenz, and possibly fuzeon. I hope that he responds, and that efurvitide and efavirenz do prove effective – if they do, he’s got a fighting chance.
I know many of you will not be able to follow much of this, but those of us who have learned to understand some of the science can glean something useful. First: this is how sophisticated HIV treatment now is – specific genetic analysis of everyone’s own viral strain and a callibrated response. Second: this patient is treatable. In fact, his options are far greater than they would have been, say, five years ago. Notice that resistance to various drugs is not binary. There’s a spectrum, and skilled doctors can provide very precise combination options to target viral replication. I’ll make a rash prediction: this guy will have a much improved immune system in a few months. As long as he doesn’t touch any more crystal meth.
The Dish 