thank u, next

March 21, 2019

“Only one person in human history has ever been cured from HIV infection by medical intervention. Wait . . ." *listens to earpiece* "What’s that? OK, well–correction!" That old line won’t work anymore: As of this month, there is a SECOND person who appears to have been cured of HIV infection by a very similar medical intervention.  Perhaps a third. Maybe this requires telling the story again from the beginning . . .

HIV infection is one of the great biomedical challenges of our time, having resisted both a vaccine and a cure since its identification nearly 30 years ago.  It’s been kept at bay by the profound advance, achieved in the early 1990s, of combination antiretroviral therapy (ART small molecule drugs), which has managed to keep millions of HIV infected individuals from progressing to AIDS and death. But if any of those individuals stop taking ART, like clockwork, the virus comes back in their blood. No matter what. No matter how many billions have been spent trying to stop that. Simply put, every single person infected with HIV (and every single monkey infected with the monkey equivalent SIV) who controls their virus on ART sees it come bounding back when the ART is stopped. Every. single. one. Except, until recently, Timothy Brown, the “Berlin” patient, who fortunately (?) happened to get leukemia along with his HIV and received a bone marrow transplant. Here’s where CCR5 comes in.

 

CCR5 is one of the major receptors needed by HIV to infect and maintain infection. Mr. Brown happened to get a transplant from a donor who did NOT have CCR5 (turns out not having CCR5 condemns you to …. no obvious phenotype... these people do not seem any different than anyone else, they are just resistant to HIV infection). HIV never came back in Mr. Brown, even without ART. This was not believed by the 99% of scientific “experts” in the field for many years. Fortunately, a few scientists actually listened and the theory was ultimately accepted as a true cure. This led to an infrastructure to replicate the approach and, as of this month, that infrastructure appears to have borne fruit. Interestingly, a safe CCR5 inhibitor drug, Maraviroc, has been around for ages, but does not seem to produce cures. This is likely because the viral rebound is generated from reactivation of an integrated viral genome, which hibernates happily no matter what is going on pharmacologically around it. It could also be that current “shock and kill” approaches that seek to irritate the virus into reactivating could work in the presence of the CCR5 inhibitor, but the tissues that serve as viral reservoirs remain something of a mystery.  Certainly, tissue specific approaches might be needed for any such effort.

 

 

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