Have We Found A Cure For HIV?

Human immunodeficiency virus. This is arguably the most feared virus on the planet, even with the advanced management techniques we have today. It has led to the deaths of millions of people worldwide, particularly Black men belonging to the LGBTQ+ community. Scientists have been trying to work on a cure for decades since the AIDS epidemic in the 1980s, when HIV/AIDS came to America and killed thousands of people while spreading fear and stigma. Nobody knew what it was back then. That was forty years ago, but HIV/AIDS continues to loom over our heads as we enter the 2020’s. Why does it seem like finding a cure is taking so long?

First and foremost, we need to reshape the way we think of cures for diseases. It’s a common notion that most diseases have a magical potion that you swallow to get rid of whatever bacteria or virus it is that has invaded your body. This is definitely possible for some diseases — Penicillin, Amoxycilin, and other antibiotics fight off a range of bacteria — but a lot of drugs work in different ways to help your body fight off the pathogen rather than directly targeting said pathogen. They can work by boosting your immune system, preventing the virus from replicating, or adjusting whether or not certain protein channels are allowing pathogens into and out of your cells. Cures can include functional cures, where the pathogen is non-detectable and non-transmittable even without the use of medication. Further, just because someone has a virus or bacterium living in them doesn’t mean that they are dangerous. This is particularly true with certain STI’s that have been hyped up to be ‘life-long diseases’ with ‘no cure’ like herpes simplex virus or HIV. For some people with herpes, the virus can lie dormant for their entire life, never causing problems for them nor being transmitted to anyone else. HIV is a little bit more complex because it does cause a lot of problems if left untreated. Luckily, there is a treatment that is prescribed for those with HIV called antiretroviral therapy (ART) that can actually reduce the amount of virus in their body to the point where it is undetectable and non-transmittable. It’s not a cure, though, because you still have to take medication every day to prevent the virus from beginning to replicate again. Progression of HIV into AIDS is also becoming increasingly uncommon. HIV is far from the death sentence that it once was and needs to be less heavily stigmatized. It is still not something you want to get (be safe out there kiddos!) but it’s definitely manageable.

If you do get HIV, you will have to be on antiretroviral therapy for the rest of your life or until scientists figure out a better option to treat it. ART usually involves taking a variety of medications that can take a toll on a patient’s liver, and can cost upwards of $9000USD per year. For a disease that can be so deadly if the medication is taken incorrectly (or if it is left untreated), you would think that a better option would have been discovered by now. Unfortunately, HIV is a tricky virus and it’s simply not that easy.

To understand why a cure is still being researched, we need to step back and understand the virus itself as well as its pathology. HIV is actually caused by two species of virus within the genus Lentivirus. In the Baltimore classification system for describing species of viruses there are seven different types of viruses that are classified based on how they produce messenger RNA (DNA’s close cousin). HIV falls into class VI, which has what we call single-stranded RNA retroviruses (ssRNA-RT viruses). In biology, we have a rule of sorts called the central dogma of biology. It says that when our bodies produce proteins, we start with DNA which gets transcribed into RNA before being translated into a protein. DNA-RNA-protein. Retroviruses like HIV are different because, as their name implies, they do this a little bit backwards. HIV has an enzyme called reverse transcriptase that allows it to convert RNA back into DNA! This is where it gets freaky: the virus then literally inserts the newly reverse-transcribed DNA into your cell’s genome. I’ll repeat: HIV viruses spread by putting their DNA into your own DNA. They can do this because they have a second special kind of enzyme called integrase. Once it is integrated into your genome, your body can’t tell the difference between your DNA and the virus’ — it is all just DNA. The viral DNA will sit inside the genome and wait, lying dormant, until your own cells help it replicate.

You can see why this would be a problem. The virus isn’t just floating around your body, but actively mixing its DNA in with your own. Every time that an infected cell replicates, more HIV is produced. Some genetic engineers are working on using CRISPR and related methods to literally cut the viral DNA out of the patients genome. Some are working on a way to make sure the DNA with the provirus in it will never replicate, making it dormant forever. Some are also trying to find a way to strengthen the immune system so it can detect and attack cells with viral DNA. All of these are promising! But there is another way that already has positive results (pun kinda intended). Three people have actually been able to safely stop taking antiretrovirals, and two of them were completely cured!

The first person to be able to go off of antiretrovirals was administered a treatment by their doctor specifically to treat the HIV. The antiretroviral therapy they initially went on consisted of two commonly used antiretrovirals — didanosine and indinavir — as well as a third drug called hydroxycarbamide. Hydroxycarbamide is not an antiretroviral but an antimetabolite that is supposed to be used for cancer therapy. It works by stopping cancerous DNA from continuously replicating. Whether it was the hydroxycarbamide itself, a combination of the drugs, or genetic predisposition, the anonymous patient stopped taking the medication after a short period of time to find that their immune system was now able to control the HIV infection on its own without ART. They still had HIV that was able to become active again, so they weren’t technically cured, but this was a huge step forward for researchers.

Timothy Ray Brown was the first person to ever have been completely cured. He was HIV-positive and also happened to have leukaemia; how’s that for being born under a bad sign? HIV-1, the type that Brown had, can’t infect a cell unless the cell has two specific kinds of receptors: the CD4 receptor and either the CXC chemokine receptor (CXCR) or the chemokine receptor 5 (CCR5). To treat his leukaemia, Brown required a bone marrow transplant. His donor had a rare genetic mutation that caused a mutation in the CCR5 allele where 32 base pairs are deleted and the receptor doesn’t work anymore. Most of the HIV-1 in his body could only interact with CCR5; only 2.9% could use CXCR as a coreceptor. When Brown was given stem cells with the CCR5 delta32 deletion, it mutated his cells so that the HIV virus could no longer infect them. Interestingly, even the viruses that could infect the CXCR were no longer detectable. This may be because Brown developed graft-versus-host disease during treatment, which is when the immune cells from the donor begin to attack the recipients cells as they are recognized as foreign. This graft-versus-host disease has actually eliminated HIV in six different people within the past decade, though they are still taking ART so it is unclear whether the virus will ever reemerge. When the donor’s immune cells are attacking the recipient’s in graft-versus-host disease, HIV-infected cells may be totally wiped out along the way. As you can imagine, though, graft-versus-host disease is very dangerous and can be fatal, so inducing it to treat HIV isn’t really a great option. Plus, we don’t really know why it works yet, so the risks far, far outweigh the rewards at this time.

The second anonymous man to be cured of HIV was also the recipient in a bone marrow transplant to treat cancer where the donor had the CCR5 delta32 deletion mutation. This only just happened as of March 2019! He didn’t develop graft-versus-host disease, which probably means that he had almost no HIV that could use CXCR. To be honest, I’m kind of wondering if the future of HIV treatment will involve gene therapy for the CCR5 allele, making HIV that can use CXCR likely to become the main or only kind of HIV instead. If that were to be the case, we would need to reexamine how to cure those viruses as CCR5 therapy won’t work. That being said, the donation of stem cells with the right mutation seems to be the best option so far.

Of course, there are always dangers when we talk about gene therapy. I wrote all about it in my very first article on Medium. However, this is HIV we are talking about. Timothy Ray Brown became very sick as a result of all of the treatment for both cancer and HIV, but the second patient did not come nearly as close to death as Brown. Graft-versus-host disease seems to totally wipe out HIV, but it is an awful disease that is painful and hard to fight. Inducing it to get rid of HIV just doesn’t make sense right now when there are such good antiretroviral options that make the virus non-detectable and non-transmittable while preventing AIDS from developing. The gene therapy was much less dangerous to the health of the patient, and it worked! It wouldn’t work for a patient that mostly had HIV that could use CXCR. Maybe a treatment will emerge to deal with that at some point in the future. Or maybe there will be some new advance that will lead to a safer and more efficient cure. For now, keep an eye on the news to watch for any new stories, and be safe. Get tested (even if you hate needles as much as I do), don’t share needles, and practice safe sex. If you are sexually active with someone who has HIV or you do share needles (don’t share needles!!!!!!), ask your doctor for PrEP to protect yourself — it’s really, really effective. Scientists, keep doing yo’ thing! We are closer than we have ever been to a cure. We don’t have it yet, but we are on the right track. Then, we can say goodbye to HIV forever.

This article is dedicated to the millions of loved ones who we have lost to acquired immunodeficiency syndrome.