“At The Crossroads; HIV Thirty-Five Years Later”

Since its introduction to the world thirty-five years ago, HIV is coming to some exciting, multifaceted approaches for treating, preventing and finally curing the disease.  Once considered to be the “Tombstone” disease due to little to no treatments, quickly moved to AIDS and then death, from opportunistic infections like influenza.  No individual actually expires from AIDS, but with no immune system protection, any viral/bacterial infection leading to the flu or sepsis, can end the person’s life.  Today the chronically managed disease is treatable with one ‘cocktail’ tablet per day and little to no side effects.  Historians will look back at the timeline of this disease and say, presently,  this is the beginning of the end in one of the world’s most pervasive and deadly diseases.

Finding comfort in numbers cannot always be found, especially if the numbers work against the message you want to communicate.  For years HIV is and unfortunately still is as a homosexual disease.  While this statement is irrelevant, we in researching this topic founds increased in transmission rates in other populations.  Injectable illegal drugs have lead to an increase of HIV infections due to the decline cost of heroin.  Drugs, like fentanyl, are cut (mixed) into the heroin by drug dealers to increase the potency and ramp up addiction rates in their clients (users) for to rapidly move their product for personal capital gain.  This has resulted in a surge needle sharing and a sharps used during the administration that has ramped up  HIV transmission rates.  The greatest problem is ignorance of not knowing they are infected with HIV; possibly not finding out until the infection transgresses to where the person is admitted to a medical center.

Even though drug use is increasingly becoming a rising population for transmission, the stigma mostly surrounds the same population.  Popular thought remains that the quintessential stereotype of a ‘HIV Positive Person’ is a gay man and for ‘all intensive purposes’ is the reason that HIV came into existence and is proliferated.  In actuality we find that heterosexuals are proliferating the disease at an equal rate as the LGBT community.  Science consistently shows that the virus’ biased to one’s sexual orientation is non-existent and for all intensive purposes,  it is not a ‘gay’ disease.  This virus’ is incredibly pervasive and can be contracted by nearly 99% of the human population.  The conclusion to this non-existent bias is that  to any individual that freely engages in the human experience, can contract the infection.  An article posted by the CATIE organization, notes that the most vulnerable location for the transmission of HIV, is via the rectum.(1)  The research behind the vulnerability is due to the mucus created by the body to protect tissues and membrane as objects pass through the colon. This mucus is made up of immune cells; white cells charged with protecting the body via the process of the immune system.  Since the virus preys on these cells for replication purposes, it’s an easy entryway into the body.  For this reasoning, the gay community has a high level of transmission.  But if you cross reference those numbers to the heterosexual community with the aforementioned rise in injectable drug use, there is a greater overall transmission rate in that population for HIV.  There is also a paradox to Viral Hepatitis infections in relation to the topic of HIV.  The Department of Veterans Affairs (VA) states that research is not able to provide credibility to the idea that Viral Hepatitis can be contracted by the receptive partner during anal intercourse; “there is no proof that the virus can be transmitted during anal intercourse”. (2)

The pervasive abilities of HIV is the reason we have yet to cure the disease.  The prevalence of the virus can be found in the research on how it invades the body once transmission to the host occurs.  HIV belongs in a  class called a retrovirus; meaning, it uses a host cell and via the process of reverse transcription to recode our own deoxyribonucleic acid (DNA) from it’s ribonucleic acid (RNA).(3)  The virus is able to achieve this replication process by invading the white cells, coined ‘Killer Immune Cells’  (T-Cell). This is the only entry way for the virus; it has no other form of entry for infection.  The CD4 protein, the virus’ receptor responsible for the binding process, ‘sticks’ the virus to the T-Cell  The immune system’s T-Cell has another protein called CCR5; this protein allows the virus to gain access and perpetuate the T-Cell.  A handful of individuals have a mutation in their CCR5 protein, termed the delta32 variant gene, that renders the protein incompatible to the viruses invasive protein receptor, effectively making them immune to HIV infection. (4)   Once the virus is able to attach to the person’s T-Cell, it injects its RNA into the host cell; effectively writing its own code into the individual’s DNA.(5)  The replication fidelity process generates a rate of copy error is extremely high and produces many mutations making the disease cure hard to calculate.(6)  HIV is also able to lay dormant in bone  and teeth tissue.  This ‘dormant status’ allows the virus to indefinitely hide itself until environmental  threat(s) no longer exist; hence why patients need daily medication to keep the infection at what is called undetectable levels.  Undetectable levels of a virus in the host’s blood is defined at less than fifty copies per millimeter (< 50 copies per mms).(7)  This status renders transmission of the virus nearly impossible in sexual activities.  Once the host’s T-Cell count is measured below two hundred cells per millimeter (< 200 cells per mms), the HIV infection becomes Acquired Immunodeficiency Syndrome (AIDS).(7)

Life with HIV has transformed from a quick termination to a simple chronic disease.  As we face a future epidemic of obesity leading to a rampant increase of diabetes type two, we still talk of HIV being the sinister disease that has a terrible stigma that haunts their hosts.  We seem to not want to  discuss the true reality of the disease; chronically manageable.  Manageable diseases such as diabetes, is a disease that eventually will cause a slow but sure death from multiple comorbidities like that of hypertension.  This is also on top of the fact that many diabetics are obese, out of shape and suffer more than just the main illness.  Dr. Max Pemberton stated his personal belief from the research we know he states that “as a doctor, I’d rather have HIV than diabetes”.(8)  Eventually all diabetics digress from, a single, daily oral pill to multiple pills just for that one diagnosis and then more as diabetes leads to other comorbidities.  In a mere matter of time, oral diabetic drugs no longer work and lead to insulin injections after all meals and for any blood sugar spikes.  For HIV positive individuals; in nearly all  cases, it’s a simple tablet that consists anywhere from two to four medications in combination, per single pill, per day.  Simple treatment; making HIV less costly, more manageable and higher quality of life for the individual.(9)  The greatest struggle is medication adherence for many individuals; doses cannot be missed. But with no outward indications visually of the infection like shingles or diabetic nerve pain, sometimes lack of physical reminders can lead to forgetfulness.  Also a daily medication can also motivate depression as the person is constantly reminded daily of their disease and can be left  feeling as if they are “a second class citizen”.  New treatment options are on the near horizon.(10)  A bi-monthly injection could replace the need for an daily oral tablet.  Adherence to six injections a year compared to 365 tablets oral consumed is more efficient, time and cost savings, less stigmatizing and better for directive medicine than the daily oral pill.(11)

Today HIV is a chronic, yet simply treated disease that thousands live with each, but where do we go from here?   The pervasive nature of this virus means that the cure will require a multifaceted approach to inoculation, treatment and a cure.  There are several key requirements reach achievement to end to this disease.  First, we need to repair the DNA that the virus perpetrates its RNA.  Earlier last year,  Temple University announced that they have accomplished this requirement; sadly, little or  little or no fanfare occurred at the announcement of this major timeline milestone.(12)  They were able to extract the DNA code out of the T-Cell, snip out the bad code in the DNA strand and applied the corrected strand back into the cell.  This cures the infected cell and prevents reinfection; once reinstated into the host, the body will replicate the fixed deemed a more superior T-Cell, eliminating the virus only infection entry point.  Applying the same process of remastering T-Cells, scientists at the University of Pennsylvania are using this approach to treating terminally ill cancer patients.  They extract roughly a billion T-Cells from the cancer patient, reprogram each cell and reinstated them into the the original host’s body.  Ten days after the procedure, the patient’s body produced a massive fever, blood pressure dropped to a near deathly low and was moved to intensive care where doctors feared he will die.  A few weeks later, the patient fully recovered and doctors calculated that nearly two pounds of cancer cells of a blood cancer called leukemia were destroyed.(13)

The remastering of the T-Cell is one of the keys to success, next we need to figure out a way to how to deal with a another pervasive behavior of the virus; the ability of HIV to go dormant and despair.  Several very unique times where the HIV positive individual ‘seemingly cured’ of the infection and  medication ended, were greatly saddened when the infection returned.  The virus is able to remain dormant and can ‘wake up’ to start the progression of infection each time medication is discontinued.  For this reason, the antiretroviral medications have not cured the disease like that of a rival, Hepatitis C.  Finding a way to reanimate the dormant viruses and eradicate their existence in the host is another tasked solution that is slowly gaining ground.  Scientists made an unexpected discovery with HIV patients who are struggling with alcoholism.  A drug called disulfiram, which is  used to combat alcoholism, was found to increase the viral load in the  HIV positive alcoholics population in the study.  What they found out is that disulfiram at the highest dose given caused dormant HIV to “wake up”.  Once reanimated, traditional retro-antivirals will be able to eradicate and prove an end ot the infection; assuming all of the dormant HIV copies were ‘awake’.(14)

Lastly we need to need to figure out a plan to reform the immune system; enhance and create tools that will combat all infection, including cancer.  This plan will be the solution will leverage efficiency and the most powerful tool of all combat disease; the immune systems.  Via innovations in science and technology, Temple was able to restore the HIV infected T-Cell DNA back to its host specific original base code and ‘patch up’ the problematic CCR5 protein.  Alongside the treatment cure, the key of prevention needs to exist to ensure the last few days of the virus’ existence cannot find a new method of transmission.  A new trending approach for a vaccination hypothesis, called sequential immunizations, could lead to a way to teach the immune system to build specific antibodies that would typically be created at various parts of an HIV infection contracted in humans.  A series of specifically tailored antigens, are administered at specific times to the person needing inoculation.  Negative patients’ immune systems can be taught to fight off a myriad of the HIV viral mutations.(15)

Continuing on the theme of the remastered immune system, medical science has developed technology helping in the fight against acquired infection. Treatment and prevention breakthroughs in technology, utilizing nano-particle material such as graphene and mesoporous (MSRs) silica rods, new tools are being created that form injectable three dimensional lattice structures.  This is a will be a ‘game changer’ when it comes to treatment and prevention.   Innovative technology of this nature can be used for direct targeted treatment in cancer by delivering medication only the infected area compared to oral, metabolism medication or chemotherapy.  These lattice structures also can be leveraged to provide a location for different types of immune cells to hide in large numbers.  Once the lattice structure arrives near a rogue virus or malignant neoplasm, the T-Cells can ‘fly out’, attack the invader, in numbers and effortlessly destroy the enemy.  These types of structures would also allow for dendritic cells of varying types, a ‘place to hide’ in one location, to keep watch for foreign invaders.  Dendritic cells alert the lymph nodes of intruders; the lymphatic system proceeds to create the correct antibody response and those T-Cells rush and destroy the outsider.(16)

Some final words on where we were have been, presently today what the future holds on the topic of  infectious disease, specifically HIV.  Thirty five years later, if not treated, an HIV infection will lead to the diagnosis of AIDS and eventually death.  Complementary to the aforementioned, at the present time, HIV is quite possibly the quintessential definition of a chronically managed disease.  Unfortunately the stigma around HIV positive individuals is crippling and currently is propelled by willful ignorance in our society largely due to the lack of scientific and health education.  While HIV is a perniciously invasive retrovirus; it has its flaws and can be stopped.  We will achieve this outcome through breakthroughs in medical technologies, genomic calculations, repairing weaknesses and enhancing the power of the immune system.  This same approach is being used as a future cure to cancer and will help provision the prevention of possible new infections currently known and unknown.  While we will not be able to treat and cure everyone, education in general is key and we will do our part to research, education and respect every person, because that is the greatest outcome we can provide for humanity.

References and Resources:
  1. Getting to the bottom of it:  Anal sex rectal fluid and HIV Transmission.  CATIE; James Wilton, Fall 2014.  http://www.catie.ca/en/pif/fall-2014/getting-bottom-it-anal-sex-rectal-fluid-and-hiv-transmission
  2. Viral Hepatitis.  U.S. Department of Veterans Affairs, http://www.hepatitis.va.gov/patient/daily/sex/single-page.asp
  3. Retrovirus. Wikipedia. https://en.wikipedia.org/wiki/Retrovirus
  4. The Evolving Genetics of HIV.  The Tech Museum of Innovation; Stanford University, 2013.  http://genetics.thetech.org/original_news/news13
  5. Reverse Transcriptase. Wikipedia, https://en.wikipedia.org/wiki/Reverse_transcriptase#Replication_fidelity
  6. Replication Fidelity. Wikipedia, https://en.wikipedia.org/wiki/Reverse_transcriptase#Replication_fidelity
  7. Fact Sheet: Undetectable Viral Load.  Beta Blog, Emily Claymore. November 4th 2013. http://betablog.org/fact-sheet-undetectable-viral-load/
  8. “As a doctor, I’d rather have HIV than diabetes.  The Spectator; Max Pemberton, MD, April 19, 2014. http://www.spectator.co.uk/2014/04/why-id-rather-have-hiv-than-diabetes/
  9. How HIV Became a Treatable, Chronic Disease. The Conversation; Allison Webel.  December 2, 2015; http://theconversation.com/how-hiv-became-a-treatable-chronic-disease-51238
  10. What is HIV/AIDS?.  AIDS.gov; revised, 12/31/2015. https://www.aids.gov/hiv-aids-basics/hiv-aids-101/what-is-hiv-aids/
  11. How an Injectable HIV Treatment Would Change Lives.  Advocate; Tyler Curry.  January 11, 2016; http://www.advocate.com/commentary/2016/1/11/how-injectable-hiv-treatment-would-change-lives
  12. Temple scientists eliminate HIV-1 from genome of human T-cells.  Temple Now, Meaghan Bixby.  March 21, 2016, http://news.temple.edu/news/2016-03-21/temple-scientists-eliminate-hiv-1-genome-human-t-cells
  13. An immune System Trained to Kill Cancer; The New York Times.  Denise Grady; September 12, 2011.  http://wyss.harvard.edu/viewpressrelease/183/injectable-3d-vaccines-could-fight-cancer-and-infectious-diseases
  14. Short-term administration of disulfiram for reversal of latent HIV infection.  The Lancet HIV Journal, multiple authors. November 16, 2015, http://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(15)00226-X/abstract
  15. Sequential immunizations could be the key to HIV vaccine.  Newswire; Rockefeller University. Zach Veilleux; June 18, 2015.  http://newswire.rockefeller.edu/2015/06/18/sequential-immunizations-could-be-the-key-to-hiv-vaccine/
  16. Injectable 3D vaccines could fight cancer and infectious diseases.  Wyss Institute; Kat J. McAlpine and Caroline Perry. December 8, 2014; http://wyss.harvard.edu/viewpressrelease/183/injectable-3d-vaccines-could-fight-cancer-and-infectious-diseases