Unit 2 Project: The Cure to HIV

HIV awareness ribbon by Trygve Utstumo

The human immunodeficiency virus, one that has baffled both researchers and doctors alike since the discovery of its existence. Unlike other viruses, your immune system cannot fight off HIV, it affects cells in your body known as CD4 cells (also referred to as T Cells). These are the primary fighters of your immune system and overtime they are destroyed by the HIV virus leaving the body susceptible to any number of other infections and diseases. Modern medicine has led to treatment known as antiretroviral therapy (ART). This is a combination of HIV medicines often referred to as a “drug cocktail” (“What is HIV/AIDS?”). With these medicines a person can live virtually as long as those without the disease, however it does require daily medication. However, I feel that researchers and scientists have lost site of the true endgame, to eradicate this virus from the face of the earth. The scientific community is divided on what steps to take to get closer to the cure. The cure to HIV has been sought after for a long time now and I am confident it is coming to a close, offering relief to family and friends as well as a newfound sense of safety for the public, however, in order for this to happen we need to ease off of antiretroviral therapy, a new therapy method without NRTIs needs to be discovered, and research on current more experimental methods of treatments needs to continue. (“What is HIV/AIDS?”)

Now one might wonder why I think the way to find the cure is to ease off of the one treatment that has been prolonging life in patients. Just to be clear, by ease off I do not mean we need to cut it cold turkey and leave people to suffer, continuing antiretroviral therapy is currently our only consistently effective way of combatting HIV. What I mean is that we need to begin focusing our efforts on other forms of treatment, while ART is a great preventative measure it is not a cure. However, in the nature editorial “The HIV epidemic can be stopped”, the author is under the impression that ART will be what cures the world of HIV. I have a few problems with the way in which they look at this problem though. First off, the author states that “Treating people with antiretroviral drugs as soon as possible after their diagnosis, it seems, not only prevents death and disability due to the disease but also prevents virus transmission.” (“The HIV epidemic can be stopped”) According to this author, these are the reasons ART is the cure for HIV. My gripe with this is that this is not a cure for HIV, it is a band aid. What it comes down to is that this author proposes we find a way to suppress all HIV cases to the point in which it can no longer be spread and then for all intents and purposes just let everyone with the virus eventually die out resulting in eradication of the disease. To me, that is not a cure and it is wrong, allowing people to suffer with a horrible virus should not be the answer. However, the answer it seems may be right underneath our noses. (“The HIV epidemic can be stopped”)

Nucleoside Receptor Transcriptase Inhibitors (NRTIs), these are contained within the the ART medicines administered to patients and they may be the problem with the treatments. ART extends and adds comfort to the patient’s life with the downside being lifelong treatment. Patients who are removed from the treatment and subsequently receive no alternative forms of treatment experience a swift rebound of the virus that eventually leads to death. The problem with this are these NRTIs, it has been hypothesized they are the reason this lifelong treatment is required. If Florian Hladik of F1000 Research is correct, then what is occurring is that the NRTIs are “promoting the survival of cells with integrated provirus” (Hladik). A provirus is the genetic material of a virus that is incorporated in a host cell and replicates as the host cell replicates. So in layman’s terms these inhibitors are allowing cells that are making more copies of the virus survive. When the source is being preserved, no matter how many of the surrounding infected cells are eliminated, the process is proven to be. Hladiks proposal is that the cure for HIV is much simpler (in relative terms) than we think. All that needs to be done is creating a cocktail that provides all of the same benefits and affects as the current treatment without the addition of NRTIs. This will prove to be quite a task because a majority of the major drugs used to combat the virus contain these inhibitors (Hladik).

Unfortunately, this is all currently hypothetical and more research needs to be done. While that is being done it is imperative that as a whole the research community needs to look onward to other forms of treatment being currently tested. There has been one case of a patient being cured, he has earned the moniker “The Berlin Patient” (Fauci). This patient was given a very risky procedure with a high mortality rate known as hematopoietic stem cell transplantation (HSCT). HSCT is a transplantation of hematopoietic stem cells (HSCs), which are the blood cells that create all other blood cells, which in this case was allogeneic which means they are from a donor. HSCs are found in bone marrow and umbilical cord blood (“Hematopoietic Stem Cells”). Interestingly enough the patient was also diagnosed with leukemia thus requiring pre-transplant therapy, which includes rounds of chemotherapy to destroy cancerous cells and also prepare the bone marrow for new stem cells (Mayo Clinic Staff). The curing of HIV in this case was incidental in some ways because it was primarily leukemia not HIV that as the authors stated “tipped the risk-benefit evaluation in favor of HSCT to cure the malignancy” (Fauci). Also the transplant donor cells were resistant to HIV with a mutation in the CCR5 gene which effects the co-receptor that is most commonly used by HIV strains when entering the human body. What this all boils down to is after transplantation the leftover HIV had no targets to make a rebound with, and the patient is still clear of all detectable signs of HIV and currently receiving no ART (Fauci).

Picture by Juhan Sonin

Looking in on a similar case with a very different outcome is the “Mississippi baby”. This was a case of a baby who was born HIV positive to a mother who received no treatment during pregnancy. Treatment for the child began when she was 30 hours old, stopping ART at 18 months. The child then remained off of the drugs for the next 27 months. This was thought to be a gigantic breakthrough in the fight against HIV and a federally funded clinical trial to see if these results could be repeated was to begin, however it seems that her HIV infection has now rebounded. The clinical trials are now being reevaluated, Anthony Fauci who is the director of US National Institute of Allergy and Infectious Diseases says the “study is still in play” (Ledford). Doctors are still unsure of what has caused this rebound in the young girl, she was tested every 6 to 8 weeks for HIV and all seemed normal until her CD4 immune cells began to drop. If the hypothesis of the authors previously mentioned is true than it means the cells that contained the provirus were silently hiding away until able to begin replication again thanks to the NRTIs in her system from treatments (Ledford).

This why we need more effort and funding to be funneled towards discovering a cocktail that includes no NRTIs as well as alternative methods of treatment like the HSCT. If safer methods of experimental treatments can be created, working out all of the kinks then we may just find the cure for HIV within our lifetime, possibly even by the year 2030. If we begin to target our efforts toward these more experimental methods, we may come out with something that has a 100% success rate to cure with a mortality rate that is little not nonexistent. Research just needs to be constantly looked at, then looked at again and then reevaluated and analyzed in a different light so that these scientists see their methods from all perspectives, leaving no stone unturned. One article that reinforced this argument was published in JAMA and talked explicitly on the feasibility, discovery, and implementation of different methods and proposed cures of HIV. This article spoke explicitly on the way researchers need to go about designing these methods to cure individuals. It outlines that first as a researcher you must look at your proposal and ask if it is indeed feasible. That is, is what you are trying to do possible and can it be accomplished within reasonable borders. Meaning no unnecessary harm will be done to any patient and will not bring rise to another problem. Next is the discovery, testing any and all possibilities. Looking into all of these different methods, constantly tweaking them and trying new combinations of these drugs until one of them show some possible signs of success. Then run with it, complete multiple trials, show it to other researchers and gain their opinion on it. When complete confidence is gained, it is time for the implementation. Put the wheels in motion, begin distribution reach any and all cases possible.

In conclusion, the nature article “The HIV epidemic can be stopped” grossly underestimates the problem and makes claims that cannot be substantiated by any cases out there. What is proven currently is that ART in itself is not a cure nor does it look like it will be, however it appears the fault within it has been found and with enough effort and ingenuity the possibility to finally cure HIV is within our grasp, all it will take is the right combination of drugs that can perform the same effect as current medicines, without NRTIs which appear to be shielding the host viruses. While this purported cocktail is looked into, alternative treatments such as the HSCT that with some tweaks and extra measures taken can be cures for complicated cases such as “The Berlin Patient”. All in all, the cure to HIV will come from a new drug mixture, something never used before and the consistent funding of the current treatment will not bring us any closer to what the real end game should be, eradicating HIV.

References

"What Is HIV/AIDS?" AIDS.gov, 8 Aug. 27. Web. 07 Oct. 2015.

Fauci, Anthony S. "Feasibility and Discovery of an HIV Cure." JAMA Network. The Journal of the American Medical Association, 23 July 2014. Web. 25 Sept. 2015.

"Hematopoietic Stem Cells." National Institues of Health, n.d. Web. 07 Oct. 2015.

Hladik, Florian. "A New Hypothesis on HIV Cure." F1000Research. F1000Research, 24 Mar. 2015. Web. 25 Sept. 2015.

Ledford, Heidi. "HIV Rebound Dashes Hope of 'Mississippi Baby' Cure." Nature.com. Nature Publishing Group, 10 July 2014. Web. 25 Sept. 2015.

Mayo Clinic Staff. "Stem Cell Transplant." How You Prepare. Mayo Clinic, 5 May 2015. Web. 07 Oct. 2015.

"The HIV Epidemic Can Be Stopped." Nature.com. Nature Publishing Group, 7 July 2015. Web. 25 Sept. 2015.