Monday, March 10, 2014

More than you ever wanted to know about HIV

Before you read any further, let me apologize in advance for how technical and possibly boring this post may seem to lay people.  I am writing it because, first of all, I'm just interested in HIV.  As a disease process, it is simply fascinating, and the way we manage it medically is, in my humble opinion, one of the greatest scientific triumphs of the past 25 years.  I will readily admit that I'm a giant geek and I just want to talk about a topic I find interesting.  The second reason I'm writing about HIV is that I deal with it pretty much daily here.  That's just life in health care, and it is not specific to South Africa.  There are plenty of HIV positive patients in America, too.  Finally, I think most people (especially lay people, and especially Americans) have strong feelings about HIV, and many have an unwarranted fear of the disease.  I have always believed that the more you know about something, the less frightening it is.  If I am wrong you actually already know most of what I'm talking about (or, at the other end of the spectrum, if this is too technical for you), please leave me a comment and tell me.  I'm interested to know what you think!

I will also offer the disclaimer that I am making some assumptions on what is and is not common knowledge based upon what I feel that most educated but medically illiterate Americans know.  I fully realize that many South Africans have a better understanding of HIV basics than most Americans do.

Let's start by defining HIV.  When I was a kid and this disease was still pretty new, it seems to me that everyone called it AIDS.  There has been a shift within the last 10 years or so, and now people usually say HIV.  What is the difference? Well, it's a big one!  Human Immunodeficiency Virus, when untreated, causes Acquired Immune Deficiency Syndrome. The relatively recent change in terminology is reflective of the fact that, with modern treatment protocols, being HIV positive does not mean that you will necessarily get AIDS.

But I'm getting ahead of myself.  Let's back up here.  HIV is a virus.  Viruses on their own are not living.  They are just DNA or RNA surrounded by a protein shell.  Since they aren't alive, viruses depend on a host to reproduce.  There are two basic types of viruses.  In one type, the virus attacks a host cell and confiscates its resources to copy its own genes and protein shell, basically making lots of baby viruses.  When it has used up all the cell's resources, it destroys the cell, and all the new copies of the virus are released.  It's kind of a fast and furious cycle.  The other type of virus works a little bit differently.  When it attacks a host cell, it does it with stealth, by inserting its viral genetic material into the host cell's own genome.  Then, every time the host cell (which may for all intents and purposes look healthy) makes a protein from that region of its own DNA, it is making viral proteins, too.  When the host cell reproduces, the viral DNA is copied along with the host DNA.  So a virus of this type can stay inside a host for years, slowly causing progressively more damage over time, rather than rapidly wiping out the host like the fast and furious virus does.  You can probably guess which type of virus HIV is.  Yeah, it's the stealthy kind.

HIV is particularly interesting because it belongs to a class of stealthy viruses called retroviruses.  These viruses use RNA as their genetic material, which means that they must go through an extra step (reverse transcription) to change their single-stranded RNA into double stranded DNA so it can be inserted into the host cell genome.  The enzyme that accomplishes this process is reverse transcriptase.  This is important because human cells don't normally do this process or have this enzyme, as far as we know (although I just now found an article about an enzyme called telomerase reverse transcriptase that seems to be present in normal cells and has something to do with slowing the aging process... I must do some reading about this).  So you can see why HIV can be so destructive.  The viral RNA, which a patient's body might be able to identify as foreign and destroy, is changed to DNA and incorporated into the host, so even if the original virus is destroyed, its genetic material is still being copied and transcribed by the host cell, which thinks it is just copying its own genome!  That clever little booger!  Do you see why this is so fascinating to me?

All viruses have a specific type of cell they like to target, a host they prefer (just like I prefer curling up on a couch to sitting on a hard chair).  HIV's favorite host cell is a type of white blood cell called a helper T cell, specifically CD4.  These cells are really important in your immune system because they help other immune cells mature.  (I admit that I know very little about the immune system on the cellular level.  It is one of the most complicated topics in cellular biology, and I always dreaded that chapter in my bio courses!)  So if you don't have enough CD4 cells, you are also unlikely to have enough of the other types of white blood cells that identify and destroy foreign invaders in your body.  If your CD4 count drops, you're not just losing one fighter in the war against infection, it's like every class of weapon in your whole arsenal is diminished.  This is why HIV causes such a catastrophic decline in a patient's ability to fight infections.  Infections that would normally be glaringly obvious to your immune system will pass unnoticed, and you could get very sick from something that you normally wouldn't even know had infected you.  Also, you're more likely to get cancer, because your immune system won't be able to identify and destroy the cancer.  (Did you know that your immune system destroys cancer?  In fact, most people will develop cancer five to six times during their lifetime, but your immune system will normally identify and destroy the cancer cells.  You only get diagnosed with cancer if the immune system misses it.)

So now that we've looked at the way the HIV virus operates, let's talk about what that means for an affected patient.  We all know that HIV is spread through contact with an infected person's bodily fluids.  Currently the most common (by a landslide... no other way is even close) mode of transmission is unprotected sexual intercourse.  HIV could also be spread by getting stuck with used needle (although that is actually relatively unlikely; for infection to occur, the needle would have to be very bloody and the HIV positive person would have to have a pretty high viral load), receiving a blood transfusion donated by an HIV positive donor (again, really unlikely because blood is tested for HIV before it is transfused), and of course it can be passed from mother to child in utero (although taking ARVs during pregnancy greatly reduces the risk of passing the virus to the fetus).  So, if you contract HIV, you would initially show flu-like symptoms that would go away in a few days or weeks.  Then you enter the dormant phase, when you look and feel pretty normal.  This is essentially when the virus is doing its stealth thing and hiding, but it is also slowly reducing the number of CD4 cells in your immune system.  Eventually, if HIV is untreated, it destroys enough of your CD4 cells that your immune system isn't able to function right.  For someone to be diagnosed with AIDS, they must be HIV positive, have a CD4 count that is below a certain threshold, and have at least two AIDS specific conditions (infections or certain types of cancer that appear only in immunocompromised patients).  

Medical practitioners use two main blood tests to monitor the progress of HIV in a patient's body.  One is the CD4 count, which tells us how many CD4 cells are left.  You want this number to be high.  The other test is the viral load, essentially how many copies of the HIV virus are floating around in the patient's blood stream.  You want this one to be low.  With modern treatment, many HIV positive people have an undetectable viral load, meaning there are so few free copies of the virus that we can't find them at all.

So, recall that I said we have won the war on AIDS.  How did we do this?  With antiretroviral drugs.  ARVs disrupt the HIV life cycle.  They work really, really well, but they are not perfect.  They do not actually kill off the HIV virus that already exists in the patient's body (remember, the virus is not 'alive' so it can't really be 'killed' either).  Thus, ARVs do not 'cure' HIV, just like insulin doesn't 'cure' diabetes.  And remember, HIV is a stealthy little beast.  If you only take one kind of ARV, the HIV virus tends to become immune to the drug you're taking.  So modern HIV treatment protocols call for three different types of HIV medication from at least two different drug classes (the 'cocktail').  One of the classes is likely to be a reverse transcriptase inhibitor, which works by preventing the HIV virus from changing its RNA into DNA.  (There are two subclasses of reverse transcriptase inhibitors, one of which binds to the enzyme and inactivates it, while the other is a faulty nucleoside or nucleotide that causes reverse transcriptase to fall off the RNA chain.)  The other types of medications interrupt different parts of the HIV life cycle.  Some of these drugs prevent the virus from entering the host cell, some block the insertion of the viral DNA into the host cell genome after it has been reverse transcribed, and some prevent the splicing of viral amino acid chains which prevents the assembly of new viruses.  Using three different drugs from at least two different classes prevents the problem of the virus becoming immune to one type of medication.  There are even combination ARVs that combine the three different medications into one pill that the patient can take once per day.

ARVs must be taken every single day, preferably at the same time of day, or else that clever little virus might become immune to the cocktail.  Unfortunately, this causes us in the medical field huge problems.  There are any number of reasons why someone would default on their ARVs.  They might not be able to get to the clinic for a refill.  They may not understand the importance of taking their ARVs every day, especially once the ARVs are working and the patient feels healthy.  They may not want to display their HIV positive status so they hide their ARVs from their family, making it difficult to remember to take them at the same time every day.  The side effects (common ones are dizziness, depression, nausea, etc) could make a patient feel worse than they did before they started taking the drugs (this is especially common when beginning therapy).  Once a patient defaults their ARVs, we have to switch them to a different ARV cocktail since that patient's virus might now be immune to the previous ARV combination.

Despite their problems, ARVs are a medical miracle.  I touched on this in my six month blog post.  I can't say enough about the science behind these drugs.  If you think of all the resources devoted to finding a cure for AIDS when it was first identified, it's incredible how our understanding of this disease has progressed, and how we've used that to develop an effective weapon.  If only we could do the same thing with global warming!

So, with all our modern medicine and knowledge about how to prevent transmission, why is HIV so prevalent in sub-Saharan Africa?  I hear a lot of political and sociological explanations for this (some are valid and some are not), but I'm not going to go into them here.  I am a scientist by nature, and there is a very simple scientific answer to this question.  Sub-Saharan Africa is where the original outbreak of the disease occurred. In any global pandemic, the epicenter of the outbreak will always be the worst hit.  Period.  (If you're interested, here is how the original outbreak happened:  A very similar virus (SIV) affects chimpanzees that are hunted by humans.  SIV was transmitted from recently killed chimps to their hunters by contact with the chimp's blood, and through blind luck and mutation, became HIV.  This likely occurred in 1908, so HIV is actually several decades older than most people think.  At least according to this podcast: http://www.upworthy.com/aids-has-killed-almost-36-million-people-but-i-bet-youve-never-heard-the-real-origin-story-2.  I will validate that the part about how the 'spillover' occurred is correct, but that podcast does have a lot of speculation in it also.)  


I have no doubt that our understanding of HIV will continue to grow, and as it does, we will develop even more effective treatments, and possibly even a vaccine.  But in the meantime, we must combat ignorance about this disease.  I said at the beginning of this post that fear comes from a lack of knowledge.  If we are to eradicate HIV, we have to get over the stigma and stereotypes that are associated with being HIV positive.  The vast majority of HIV positive people aren't illegal IV drug users, homosexual, or risky with their health.  They're just people who happen to have this chronic medical condition, which is highly treatable and almost impossible to spread to others through normal day-to-day contact.  So why is there such a stigma attached to being HIV positive?  We can all commit to fighting the war on AIDS by sharing our knowledge and destigmatizing HIV.  Let's work on that, ok?

Note:  I did not cite sources for any of this information for two reasons.  First, I don't feel like citing sources, and since this isn't an academic paper, I don't have to.  Second, I wrote this mostly from my own personal database of useless trivia, which was obtained from lots of sources over a long period of time (nursing school, my undergraduate work in biology and genetics, four plus years of patient care as a nursing aid and a nurse, and a personal interest in the topic that has led me to do a lot of googling over the years.  Yeah, yeah, I know, I'm a big geek.)


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