Wait…Did a kid just get cured of HIV?

Okay, I have a ‘reputation’ on the internet. You hear some wonderful news via Google alerts or on the MSN homepage about some FANTASTIC breakthrough with HIV… and then you come to ERV to come crashing back to reality. So, you might have heard about the kid who ‘got cured of HIV infection’

Now, I hate to disappoint you all… but…

This is actually possible.

Of course I havent read the paper or any research associated with this particular case, but theoretically, it is possible.

Under ‘normal’ circumstances, HIV infection is initiated by one/few genetic variants of HIV-1.  It is an extreme population bottle-neck, but some initial research indicates that the transmitted variants are ‘more fit’, evolutionarily, than non-transmitted variants, so that one/few viruses replicate like wild-fire. This means that as the adaptive immune system is trying to ‘catch’ it, that one/few viruses are rebuilding the quasispecies (population of viruses that are all similar, but genetically distinct from one another). Weeks, months, years later, when the individual is finally diagnosed with HIV infection, the quasispecies is firmly established. When the individual starts antiretroviral therapy, there are already HIV variants in the quasispecies that are resistant to the drugs (viruses do not evolve resistance to the drug, they already have resistance before the drug is applied).  Usually, this drug escape comes at a fitness cost to the virus, so the patient has low-to-undetectable levels of HIV when they are on therapy… but its *not* zero. There is just a very low level of replication.  Every single time there is a replication cycle, the virus is still making mutations, so it is rebuilding the quasispecies *again*.  Eventually, the population stumbles upon a combination of mutations that lets the population 1) escape the drugs, and 2) have increased replication capacity, meaning the virus can go back to its old high levels of replication/disease even in the presence of the drugs. This is called antiretroviral failure. So the physician has to switch drugs, take them off drugs to see if a non-resistant variant will outcompete the resistant guys, etc.

This isnt always what happens, I am just speaking generally, here.

From what I can discern from the press-releases, things happened differently in this baby. I am going to guess Babby wasnt infected early on in utero, as this isnt so common, and when it happens is very lethal. So I am guessing Babby was infected shortly before birth, or during the birth process… However press-releases say Babby was diagnosed *at* birth, which had to have been a blood viral load test (cant do an antibody test, as Babby has Moms Abs)… so she couldnt have been infecting during birth (more common). Hm. So, lets say shortly before birth, Babby was infected with HIV. Probably one/few genetic variants, probably ‘more fit’ relative to what was in Mom, but probably *not* already resistant to antiretrovirals and more fit.

Babby already had Moms adaptive immune response working for her. And at birth, she was immediately put on antiretrovirals.

Limited genetic diversity in the transmission event + pre-existing anti-HIV antibodies + immediate drug therapy =  They might have gotten the drugs there before the quasispecies was established, thus there were no drug resistant variants present. Antiretrovirals and antibodies from Mom could do their work. Babbys developing immune system had an easier target to catch.

Its possible Babby was cured.

And this isnt entirely ‘off the wall’. In every HIV lab there is a box on the wall with antiretrovirals in it. If you get exposed to the virus, you take the drugs, and you keep taking the drugs for, I believe, at least 6 months. The idea is, if we get exposed in the lab, we might have low levels of replication, but the drugs being RIGHT THERE immediately would keep us from getting genuinely infected. I know a couple people who have had to do this, and well, they arent infected.

Its also the idea behind using antiretrovirals before you are infected with HIV. Have the drugs at the site of infection, and maybe you can stop the Big infection, the quasispecies, the drug resistant variants, from ever emerging.

So, believe it or not, Im actually NOT going to be Debbie Downer today.

There might have been a kid cured of HIV infection.

:)

But dont lose hope! I havent seen the research behind this case yet! I might be Debbie Downer about it tomorrow ;)

Comments

  1. #1 Pitchguest
    March 3, 2013

    *fingers crossed*

  2. #2 Michael Kelsey
    SLAC National Accelerator Laboratory
    March 4, 2013

    The press account from Science magazine (http://news.sciencemag.org/sciencenow/2013/03/early-treatment-may-have-cured-b.html) says that the case is going to be presented “tomorrow” (Monday 4 Mar, I think) at CROI 2013 in Atlanta (http://retroconference.org/).

    I’m unfamiliar with medical research conferences, so I don’t know if the talk itself will be available online. At least in principle, there should be more details available this coming week.

    An interesting aside in the ScienceNOW article was that the current standard of care is that mothers who test HIV-positive prenatally are immediately put on ART, and the newborn is supposed to be given AZT and nevirapine prophylactically at birth. That wasn’t done in this case because the hospital did not have them on hand.

    However, that description jibes with your analysis: hitting the initial viral population early enough prevents the infection (“quasispecies”) from establishing in the first place. Thanks much for the explanation!

  3. #3 Blake
    March 4, 2013

    Thank you.

  4. #5 Niels
    Netherlands
    March 4, 2013

    lol I love the way you start out this post, because when I read the article on the Guardian, the very first thing I did was visit your website :-)

  5. #6 Bryan
    March 4, 2013

    And this isnt entirely ‘off the wall’. In every HIV lab there is a box on the wall with antiretrovirals in it. If you get exposed to the virus, you take the drugs, and you keep taking the drugs for, I believe, at least 6 months
    This is what I thought of when I first read the article – we’ve been treating needle-stick injuries in the same fashion of this child for years, and we know that introducing the above therapy ASAP after possible exposure radically drops your chance of developing a full-on infection (from ~1:125 to about 1/10th that). Meaning, we’ve ‘cured’ people in the past using the same method, but never known who we ‘cured’ and who was simply the normal 124:125 who get HIV+ needle sticks without forming a productive infection..

    I think what makes this case is unique in that it is the first time we’ve applied the anti-retroviral protocol and prevented disease in an individual whom we are certain had the virus in their blood.

    Sadly, its not a cure that is applicable to many…

  6. #7 Mike
    March 4, 2013

    Could this have simply been a misdiagnosis? In other words, the child was never infected. Sorry, I can’t figure out from the reports whether or not this possibility had been ruled out.

  7. #8 William Bell
    March 4, 2013

    Mike, the child was retested over a period of years, she is 2 1/2 and only has been off drugs for the last 6 months, perhaps I misunderstand but I believe she would have been tested several times after birth to confirm whether or not she was hiv positive still. It wouldn’t have gone away immediately.

  8. #9 Andrew
    March 7, 2013

    Mike, from what I read, they tested the child for dead HIV cells afterwards and it came out positive.

  9. [...] for six months.  It’s not entirely clear what exactly caused the virus to be knocked out.  Erv, a blogger who knows a whole lot more than I do about HIV has a thought about [...]

  10. #11 Preston Garrison
    March 9, 2013

    Is it sensible to think of an HIV cure by engineering a site-specific nuclease to target an essential HIV sequence for cleavage and delivering the nuclease as a gene in a virus which would target the same immune cells that HIV targets? The DNA break might get repaired by double stranded break repair pathways and the cells survive, but likely with a dead HIV provirus.

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