May the odds be ever in your favor-- A 'functional cure' for HIV-1

HIV-- Its a terrible game of chance.

Odds of HIV transmission are, superficially, rather low (its no measles). And, we can make the risk of transmission even lower various pro-active ways-- antiretroviral use to keep viral loads down in HIV+ people (especially in pregnant women about to give birth), screening donated blood and organs, condom use, needle exchanges, and so on.

But people still get infected.

Some progress relatively quickly to AIDS. Some dont progress at all, and never need to take antiretrovirals. Some have huge levels of HIV in their blood. In some, their physicians can barely find any. Some have great neutralizing antibody responses. Some dont. Some have aggressive Cytotoxic T-cell responses. Some dont.

... Why????

We have some clues.

Sometimes it has to do with your genetics. Some people lack a functional copy of the gene 'CCR5', one of the primary co-receptors HIV-1 uses to infect cells, so they have a harder time getting infected. Some people have an allele, a flavor of HLA that is REALLY good at teaching the immune system how to recognize HIV infected cells.

Sometimes it has to do with the genetics of the virus. Scientists took virus out of people who progressed quickly to AIDS, and people who didnt. When they made those viruses fight-- compete for a limited number of target cells, the viruses from the fast progressors were more evolutionarily fit than the viruses from the slow progressors.

... But someone can have a 'protective' HLA type and progress to AIDS at the same rate as someone without the 'protection'.

... And Subtype B viruses normally whomp Subtype C viruses in competitions... but Subtype C viruses have had no trouble, evolutionarily, taking over Africa.

So if you tell me that John Doe was just infected with HIV, and want me to tell you what is going to happen to him-- I have no freaking clue. I can make some educated guesses, but it will ultimately come down to dumb chance.

But as I mentioned above, that doesnt mean we cant do things to pull the odds more towards our favor. The message is becoming increasingly clear, and will be a bit of a theme this week on ERV-- HIV+ people need antiretrovirals.

This first paper you have almost certainly heard about on the news-- '14 people functionally cured of HIV'

Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

I was hoping the 'functional cure' thing was a product of the media, but it wasnt. Its actually in the paper. I *really* dislike that phrase for these particular cases, and I very much prefer the 'Post Treatment Controllers' term they use.

But thats neither here nor there.

The point is, 14 Average Joes/Janes were tested for HIV-1 during primary infection (early, about a month-- not months-years afterwards). They got antiretrovirals immediately (not only when their CD4+ T-cells numbers started to drop), and took them for an extended period of time (average 3 years).

When their antiviral treatment was interrupted (read: stopped), for unstated reasons (???, this bothers me), these individuals went 48-115 months without reverting back to a 'progressor' state. Three had 'protective' HLA alleles, but 11 did not. However, while some are good and some are neutral, some are associated with rapid progression-- five of the 14 had 'bad' MHC alleles!

Long story short:

There are 14 people walking around with HIV+ cells, but low/undetectable viral loads, normal CD4+ T-cell counts, in the absence of antiretovirals. Even the ones who we would have predicted would have progressed to AIDS relatively quickly, based on their genetic profile. The scientists think this happened because the patients got diagnosed early, and were treated early.

So, cure for HIV/AIDS???


The paper authors speculate that if we treated everyone exactly how these patients were treated, we could hope to expect about 15% of the patients would respond similarly.

That means 85% would just be regular ol HIV+ patients, not 'functionally cured' (blech) Post Treatment Controllers. They would revert back in less than 6 months.

Not a cure.

Just shifting the odds in our favor.

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"Not a cure". Downer strikes!

In my world (cancer) I would call that curing some of the patients (setting aside questions of how cured these particular HIV patients really are), and would be delighted to have made that kind of progress, on high stage adrenal cancer for example. I never expected to cure them all, and not curing means dead very soon for them. I do get that "a cure" means it has to work on almost everybody when used in normal speech, and so I'm not really disagreeing, just saying that I'd be celebrating.

No cure is 100% successful. 15% is pretty terrible, but but it's better than what we had before. Of course the real life percentage would be much lower because catching the infection early is essential, but I think people are downplaying this a bit much. This is far more impressive, to me, than the baby cure. I wish they'd looked a little deeper at the virology, but I think there's a decent chance that at least some of these people have no or virtually no replication competent HIV in their bodies, either viral or proviral. I'd love to see what would happen if these patients were put back on HAART in combination with vorinostat. If there is a latent reservoir, it's probably tiny compared to most HIV infections.