I often see people wondering why HIV has evaded both a vaccine and cure for so long, despite the amount of attention and money it has received.
The HIV virus is remarkably fragile and (relatively) difficult to transmit. However, it mutates incredibly quickly compared to other viruses - an HIV+ patient may have multiple strains of the virus in their body at any one time, requiring the infamous "cocktail" of drugs as no single drug will be effective.
Vaccinations have been (so far) ineffective because they attempt to vaccinate against a rapidly moving target.
Hepatitis B, on the other hand, is a much more easily-transmitted virus, and yet we have been able to develop a reasonably effective vaccine against it[0]. For a while, it used to be standard practice to vaccinate all young children against Hepatitis B; I'm not sure if it still is.
Unfortunately, Hepatitis C, which kills more people in the US than HIV/AIDS[1], is arguably even worse - it is also much easier to transmit than HIV, but we don't have a vaccine against it either. Furthermore, because most of the public campaigns advocating safe sex and clean needles use HIV-specific language, many people aren't aware that it is such a huge threat. Like HIV, it is asymptomatic for several years, so as many as 75% of people infected with Hepatitis C don't even know it[2]:
Epidemiologically (not politically) Hepatitis C today is similar to the state of HIV in the 80s and 90s[3]. We have some medications to treat it, but they're not very effective - living with Hepatitis C is oftentimes worse than living with HIV.
[0] As with all vaccines, it is imperfect, which is why coverage across the general population is the best approach to eradication or containment.
[3] At least outside the US - the US was one of the last countries to approve HIV antiretrovirals, which incidentally is the topic of a movie currently in theatres: https://en.wikipedia.org/wiki/Dallas_Buyers_Club
> an HIV+ patient may have multiple strains of the virus in their body at any one time
It's even crazier - an infected person has enough virus, and it mutates readily enough, that somewhere in their body is a single viral particle with each single point mutation variant. Every variant is in every person.
Another important point is that its latent phase is just so dormant - and for so long (relative to other viruses). We have pretty effective drugs to kill those viruses that are not latent. But there are always survivors. In fact there are a number of therapies that do nothing but try to force the virus to become active, so that the other therapies can (reliably) kill it. And even then, there's some that stay latent ready to stochastically turn on at some point.
This is because HIV is a brilliantly designed virus (of course it evolved, it's not designed. I don't know a better way to say this though). It's a third-generation retrovirus, meaning it defeats internal cell safeguards in a very clever way, meaning that if one cell of a few types comes into contact with ~10 virus particles, you effectively have AIDS. For the flu we're talking hundreds of cells needing to be in contact with thousands of virus particles.
It evades being a target for vaccination by using internal body networks to transmit itself as opposed to the blood. The immune system inside our bodies has a sort of chemical protocol for one cell to exchange data with another. One cell approaches another, presents a specific molecule, and the cells link, exchange something (we don't know what, or why, or how for that matter), and the HIV virus slips along.
This means HIV looks at the immune system from behind all the detection mechanisms. You can look at immune cells as a mine : they have lots of traps on the outside. Trigger one of them and a massive army of huge, very angry, and very dangerous cells will overwhelm whatever triggered it (http://www.youtube.com/watch?v=JnlULOjUhSQ), and a large part of things nearby that didn't trigger it too, usually. So where does HIV hide ? Simple : on the inside of the mine, transmitting itself to other mines when through the mechanic that comes by to repair the mine and doublecheck things every now and then.
There's other virii doing this, however they don't generally hide in the immune system. But for example Bof has the same tactic. It hides on the inside of cells, then every 3-4 months or so, one of the virus particles suddenly starts multiplying and makes it's host cell explode. The virus particles immediately get slaughtered by the immune system, but not before spreading the infection.
HIV is also mutating on purpose. Part of it's DNA (yes, the virus itself has RNA, however it's a direct analog. The virus, when in operation, consists of DNA though) is dedicated to mutate. It's got a long list of mutation instructions targeting specific parts of it's DNA, generally the ones referring to the virus mantle, but there are others. Effectively it contains instructions to copy it's RNA, then change the values at position x,y,z by random values from a specific range.
And HIV generally gets things right. It doesn't ever multiply fast enough to really set of alarm bells in the immune system. It avoids entering the blood stream except to spread from one human to the next(which is why even with regular sexual contact with an HIV positive individual, it takes ~6 months to get infected), and waits just long enough for the immune system to calm down before trying it again. It does this while still spreading fast enough to very slowly increase the number of infected people.
There are a number of countries on this planet, mostly in Africa and the middle east, where HIV has gone from being endemic to worse than that. In several places it is a matter of time until 100% of the population will be infected.
It is a very, very interesting virus.
A piece of good news is that, over time (but quite fast given that this is evolution we're talking about), HIV is becoming less lethal. This is exactly because it's infecting a significant fraction of living humans (without killing them). HIV is hardly the first virus to infect 100% of the human population, and there are some indications that other such viruses were somewhat similar. It also means that the evolutionary selection criteria for HIV will match those of the human race before long, and it should at some point mutate into a beneficial influence on the human race. The only way for HIV to spread it's genes will soon be to make more humans. At that point, it's no longer a virus but a part of humans, not much different from say, your liver, and it will find some function to fulfill. And again, it's hardly the first time this is happening to the human race, and it won't be the last.
yes this is not actually showing the cell type HIV attacks. However as far as I know there is no known video of the correct cell type actually doing something. Plus it's a very cool video.
I'm not a biochemist, but my understanding is that that's less relevant than you might think, especially if you're talking about vaccinations.
Vaccines can have a number of different mechanisms of actions, not all of which involve the immune system (at least, not the way you probably think of the immune system).
For example, in 2007, scientists were excited about the prospect of emerin[0] - it turns out that by knocking emerin out of cells' membranes, it becomes difficult for HIV to penetrate the cells.
Before an individual seroconverts, it's possible for the immune system to "fight off" HIV, and this happens sometimes (which is part of why transmission rates are not 100%). It's just a question of whether this is effective enough against all strains in order to be used as a vaccine (as well as the costs or side effects of doing so).
I think the point was that a virus that affects systems other than the immune system but doesn't adversely affect the immune system doesn't generally allow damage to all other systems. As a whole, very few viruses can cause multi-organ system failure. HIV creates an internal environment that allows any and all other systems to fail.
HIV is hard to immunize against because it targets immune cells. Some types of immune cells that bear HIV-binding antibodies may actually vacuum up viruses and infect themselves. Some vaccines have increased the likelihood of pervasive HIV infection. The trick will be to make a vaccine that only stimulates the production of HIV-non-susceptible cells.
Hepatitis B mutates about as rapidly as HIV. Although it is a DNA virus, it replicates from the RNA stage using a sloppy, unreliable reverse transcriptase. (Wikipedia quotes a mutation rate of >1 per nucleotide per year.) But hepatitis B does nothing special to immune cells, so when they vacuum up a virus particle it dies.
This isn't all that surprising given that they did not receive special bone marrow, but it is very sad for these patients.
<speculation>Even in the Berlin patient, it is likely that there is some reservoir of HIV+ cells, but because his transplanted bone marrow lacks the CCR5 receptor, that reservoir cannot expand, so he appears cured (and, for all purposes, is).</speculation>
The viral reservoir of the Berlin patient has been examined and it is competent for X4 tropism. The fact that the virus has not re-infected cells (via the CXCR4 receptor) is some combination of factors/luck that we do not understand fully. The leading hypothesis is that the number of X4 tropic infectious particles are simply too low to reseed the replaced immune system.
For background I recommend the original studies of this patient (Hutter 2009, NEJM and Allers 2011, Blood), they contain a wealth of interesting information.
well then it seems the faulty assumption is that the HIV virus in his body only can attach to the CCR5 receptor, when what is likely is that some nonzero pool of virus has mutated to attach to another receptor altogether or have slightly less affinity to CCR5 but a hybrid affinity with another receptor.
These virii will then have the capability of hiding in a different cell type from immune cells, and come back later.
I think there is some confusion. The Berlin patient, the one who was transplanted with CCR5-negative donor stem cells, is still cured. Therefore, none of that explanation is needed.
Awesome; I see http://www.indysci.org/projectmarilyn/ from your profile. Looks like your fundraising starts tomorrow? I hope everything goes well. What you're embarking on has probably not been tried before and will be very interesting, so please keep us posted.
> "If you have an underlying neoplasm (tumor) like these patients had, then the risk outweighs the benefit," he said. "However, if you are doing well on ARVs and you merely want to get off antiretroviral therapy, then the risk seems greater than the benefit."
"If you have an underlying neoplasm (tumor) like these patients had, then the risk [of not treating the tumour] outweighs the benefit," he said. "However, if you are doing well on ARVs and you merely want to get off antiretroviral therapy, then the risk [of the transplant] seems greater than the benefit."
I often see people wondering why HIV has evaded both a vaccine and cure for so long, despite the amount of attention and money it has received.
The HIV virus is remarkably fragile and (relatively) difficult to transmit. However, it mutates incredibly quickly compared to other viruses - an HIV+ patient may have multiple strains of the virus in their body at any one time, requiring the infamous "cocktail" of drugs as no single drug will be effective.
Vaccinations have been (so far) ineffective because they attempt to vaccinate against a rapidly moving target.
Hepatitis B, on the other hand, is a much more easily-transmitted virus, and yet we have been able to develop a reasonably effective vaccine against it[0]. For a while, it used to be standard practice to vaccinate all young children against Hepatitis B; I'm not sure if it still is.
Unfortunately, Hepatitis C, which kills more people in the US than HIV/AIDS[1], is arguably even worse - it is also much easier to transmit than HIV, but we don't have a vaccine against it either. Furthermore, because most of the public campaigns advocating safe sex and clean needles use HIV-specific language, many people aren't aware that it is such a huge threat. Like HIV, it is asymptomatic for several years, so as many as 75% of people infected with Hepatitis C don't even know it[2]:
Epidemiologically (not politically) Hepatitis C today is similar to the state of HIV in the 80s and 90s[3]. We have some medications to treat it, but they're not very effective - living with Hepatitis C is oftentimes worse than living with HIV.
[0] As with all vaccines, it is imperfect, which is why coverage across the general population is the best approach to eradication or containment.
[1] https://en.wikipedia.org/wiki/Hepatitis_C#Epidemiology.
[2] http://m.cdc.gov/en/VitalSigns/hepatitis-c
[3] At least outside the US - the US was one of the last countries to approve HIV antiretrovirals, which incidentally is the topic of a movie currently in theatres: https://en.wikipedia.org/wiki/Dallas_Buyers_Club