Managed to catch the documentary House of Numbers online, and I gotta agree with the review, that it is an interesting piece.
As a virology student, there are quite a number of facts that are mentioned suggestively that could create misunderstandings... but also some fresh findings.
As a films student, there is a great use of snip editing, and piecing together, to build up on the notion from the producer's perspective. While this helps in giving quick contrast on topics, you do start to question if the speakers were going to carry on and say more, to substantiate their point, or a "this is like this, but there is also..."... with the second part snipped out.
In a world where the public is into conspiracy theories and skeptical of scientists working for huge profit making pharmaceutical companies, its easy to see how this movie appeals to the masses. Interestingly, there are a number of journalists and chemists and even physicists giving their take on their expert "biological" views of HIV and AIDS. These even included Christine Maggiore, an AIDS denialist, who coincidentally died from AIDS-related symptoms.
Personally, I must say that the movie does bring across the startling message that few people can actually tell apart HIV and AIDS. By definition:
HIV: Human Immunodeficiency Virus (The pathogen)
Infection: Invasion and multiplication of a pathogen within the host that might result in disease
AIDS: Acquired Immune Deficiency Syndrome (The disease)
Thus, unlike what the movie challenges as "bad science", it is not true to say that HIV only results in AIDS, and AIDS is only caused by HIV. Disease and pathogen are not a simple direct cause and effect for most cases as there might be complications. Take the common cold, it could be caused by either Corona virus (as in SARS-CoV) or Influenza virus (H1N1). Take the Varicella zoster virus, it causes chicken pox and also shingles in later life. It is just more likely that if you have a cold, you are down with Influenza, and if you have Varicella zoster virus, you will get chicken pox, but that does not limit it.
As the movie cites, its true that Poppers (alkyl nitrites) does wreck the immune system, and thus the user might manifest a weakened immune system, and even show symptoms of AIDS. But, just because they do, you can't correlate and say that oh, that must be the only cause of AIDS, HIV is a myth. What about all the non-Popper users who have a retro-virus infection and manifest AIDS? Are they now the outliers?
.... If you wanna read on about my review of the movie Click here ^^x...
Something else that is not shown clearly in the movie, is the body's response to infection, and the effects of HIV. I feel that this is important for the public to get an idea of the impact and effects of the testing, and symptoms.
So, here is a simplified overview of the process... in a normal infection, the virus is picked up by dendritic cells (innate immunity), which gets activated and presents the virus to the B and T cells (both are types of white blood cell), thus activating them.
2 things can then occur... the activated T cell can then kill the infected cell directly (CD8/NK T cells), or the activated B cells can produce antibodies that hinder the virus and promote its degradation.. there is also an important group of CD4 T cells that help activate both pathways (CD8/NK T cells + B cells).
So, what happens when you have a HIV infection? Recent papers in Nature have showed that HIV is able to hijack dendritic cells and prevent them from recognizing the virus. Thus, the virus is picked up by the dendritic cells, but it does not activate them. The virus hides within the dendritic cells, until it comes in contact with T cells. It then transfers over to the unactivated T cell and infects it, especially the CD4 T cells. In addition, unlike other viruses that rapidly replicate and lyse cells, HIV is able to integrate its DNA into the human DNA, and lay dormant.
The result? There is a long period of dormancy, in which the virus hides within the CD4 T cells, before being reactivated, and thus slowly killing them 1 by 1 (this explains why the mathematical model doesn't fit). Such replication methods, have been well studied in the lytic and lysogenic cycles of bacteriophages, the viruses that attack bacterias. Thus, its not hard to imagine that a similar process might be adopted by HIV.
At such low levels, the virus is almost undetectable and the patient looks normal and healthy. However, in reality, the CD4 T cell count is decreasing. As mentioned earlier, CD4 T cells play a crucial role in activating both pathways to remove infection. Thus, finally after a number of years, the patient reaches a low in CD4 T cells and this results in the immune deficiency. The patient then suffers from various rare diseases that would have otherwise been easily cleared by a healthy immune system.
Understanding this, you should now realise why it is misleading to say that HIV testing is inaccurate, because HIV positive patients are healthy and fine 10-20 years after their diagnosis. The virus is a time-bomb, slowly eating away at your CD4 T cells, it is only after many years, at the end stages of infection, when the T cell count is low, will one finally see the symptoms. In the early stages, patients will look perfectly healthy. The latency period also means that there is few HIV virus free floating in the blood, thus why it is possible for a HIV positive person to have sex with another and not transmit the disease. The complicated relationship of dendritic cells and T cells, also highlight the reason why initially scientists have found it hard to replicate the virus in cell cultures.
Next, is the sensitivity and specificity of the tests. Indeed, a rapid test kit is a cheap and fast way to get a diagnosis, but it shouldn't be taken as a confirmation. It was not made to be 100% perfect. It is like a pregnancy test kit, cheap and fast, but prone to false positives, it is not perfect. Just like how you would have an ultrasound to confirm pregnancy, further tests should be done for HIV.
So, is there a way to confirm it? Pregnancy can be confirmed through the visualization of the fetus. So what about viral infections? For more infectious pathogens, you could detect them visually in the blood, like SARS-CoV and malaria. However, for HIV, as the virus stays latent and dormant, it is hard to do such visual confirmation.
So what does the ELISA test do? In ELISA, we are detecting the antibodies produced by the patient against HIV antigens (different parts of the virus). This is based on the theory that antibody will only be produced if the patient is exposed to the HIV virus. It should be noted that this is the same theory as the rapid test kits.
So how do false positives occur? Well, your body might produce antibodies that recognize something similar to the antigens and cross react with it. This is commonly seen in auto-immune diseases whereby antibodies produced wrongfully recognize host cells. It is also very dependent on the washing steps to remove unspecific binding.
What about Western blots? Similarly, it also detects the presence of antibodies against the viral antigen. Thus, it also suffers from the same possibility of a false positive, although it doesn't involve washing and thus is more specific and sensitive. Another issue with antibodies is that they normally take days after the initial infection to be formed. Thus, during this window, there are no antibodies produced. Antibody levels also decrease with time, that why you need booster shots for your vaccines. Thus, over time, you might turn from a positive into a negative.
So, are there better tests? Yes. There are now Viral load tests and Nucleic acid-based tests... both of which tries to detect the virus directly. However, as with any test, they are not 100% perfect. Even the best tests are only 99.99% sensitive or specific. There is always a chance that the virus might be missed or the components might not detect it. Viruses are always mutating, they are not constant.
The only sure way would be to physically detect the virus, but this involves electron microscopes and is too costly. The virus also lacks distinct morphology, that allows it to be easily recognised. So, its true that we do lack a undisputed testing method. The best we can do at the moment, is a compromise. By using detection methods based on different principles, we can reduce the chances of a false positive or negative. A rapid test, followed by ELISA and Western blot, is a bad idea, as all 3 methods work on the same principle of antibody detection. Viral load and Nucleic acid-based tests, detect the virus directly, but are only most useful during initial infection, when the virus has not gone into latency.
So yes, we do need better methods of testing, since diagnosing HIV-positive is like giving a death sentence. But that's the limitation, even for modern science. Even now, for most diseases, we don't usually diagnose by definitively saying what the causative agent is. Usually its diagnose by the symptoms, like a runny nose or pox. But the problem with HIV infection is that, the infection itself doesn't kill you. You don't die from immune deficiency. You die from diseases that occur because you have immune deficiency.
Thus, that is why there is a long list of diseases linked to AIDS. It is not true to say that when you have AIDS, you will sequentially have the other diseases. If you are in a clean room, you could avoid most of them. But, by having AIDS, your body is so weakened that you literally could get anything under the sun. Thus, the long list of rare diseases that a normal immune system would have no problem fighting off.
This does not mean that the list is useless. It is useful, since you only expect those diseases in the aged or chronically ill, and not in otherwise healthy young adults. By having those rare diseases, it is indicative that there is a defect in your immune system, likely due to AIDS. In areas where modern tests are not available, this is useful in a way. Although usually such patients would be in late stage AIDS and you can't save him/her, this knowledge could allow you to take more precautions and try to curb the spread of infection.
An interesting remark made commonly in the movie is that after 20+ years, no cure has been found for AIDS, and that is because the causative agent has not been found. Well, if you consider malaria and TB, the causative pathogens has been known for years, and yet, due to the unique life cycle of the pathogens, no cures have been found too. Should we now start to doubt the literature behind those diseases too?
The first treatment for HIV infection, AZT (a nucleoside inhibitor), is a chemotherapy that works by disrupting DNA synthesis. However, as DNA is also present in host cells, side effects are expected. Such damaging effects are also seen in cancer chemotherapy, whereby the host cells are also affected. The idea is that virus replicates faster than host cells, thus hopefully the drug will have more damage on the virus.
The downside is that, AZT treatment doesn't kill the virus outright, it just slows it down. To eradicate the virus completely, you would have to give a lethal dose that would disrupt all DNA synthesis, including that of the host, thus killing the patient. Over time, through natural selective pressure, HIV can mutate and become resistant to AZT, thus AZT treatment would just do more harm than good.
Today, we have other options like Protease inhibitors. These are targeted at the viral's unique machinery and thus have less side effects to the host. We also have fusion inhibitors. However, through natural selection, the virus could also become resistant to it over time. The main problem with viral treatment, is that viruses hijack the host's machinery, so by targeting the virus, you could easily end up targeting the host cells.
So, are we always going to fight a losing battle? Well, it is possible that mankind too will evolve and mutate to outwit the virus. It has been identified in both mice and people that a mutated CCR5 receptor, the receptor used by HIV to bind to human cells, results in a milder version of infection, or even conferred immunity.
Recently, it has also been showed that the immune system itself, if manipulated, is able to keep HIV in check. Thus, in the end, one's immunity might be the best weapon against the virus, provided the virus doesn't wipe it out first. That's what it is meant at the end of the movie, that a stronger immune system could help, and that solving poverty will improve their standard of living.
It should be noted, that poverty correlates not only with AIDS but also malaria and TB. Correlation is not causative. True, without poverty, the poor would be better fed, and have better immune systems, and probably survive better against these diseases. However, as mentioned, poverty alone doesn't explain the occurrence of AIDS patients in developed countries.
In all, the movie is good as it allows us to reflect upon the depth of our understanding about the issue. However, the sad point about the movie is that it confuses you, before leaving you hanging there, without showing you the possible answers, rather suggesting that there are no answers. As the saying goes "alittle knowledge is a dangerous thing". One should look beyond for answers, and clarify on the facts. Not everything is as bleak or without answers, as the movie suggests.