HIV: Where are we now?

MM2

In 1981, the Centers for Disease Control (CDC) released a report describing HIV for the first time.  It detailed the account of five young gay men in Los Angeles who had fallen ill to opportunistic infections, which a healthy person can fight off fairly easily.[3]  There was no treatment for this disease that was causing otherwise healthy people to succumb to infections that the immune system could normally fight off, and soon the HIV epidemic was in full force.

Scientists scrambled to find treatments, but the virus proved elusive to study and combatting it seemed impossible.  There was no effective treatment for HIV until the development of antiretroviral therapies, or ART.[1] Dr. Paul Wender, a chemistry professor at Stanford who conducts HIV research, explained to me how the approaches to research have changed over time, specifically with regard to the development of ART. “[ART] changed things dramatically as rather than people dying of the disease, individuals on ART were able to live with the disease. ART has been improved in many ways since, with better agents and even better ways of taking the drugs.” [1] ART has truly revolutionized HIV treatment.  A study done by consortium of researchers reported that the life expectancy of HIV positive people in North America is approaching that of the HIV negative population.[4] This is astounding considering that, a few decades ago, an HIV diagnosis was effectively a death sentence.

MM1“HIV particles budding from a lymphocyte”, by R. Dourmashkin is licensed under CC BY-NC-ND 2.0

 

What is ART?

Antiretroviral therapies (ART) are drugs that suppress the HIV virus.

“Antiretroviral” refers to a drug that targets retroviruses, like HIV.  A retrovirus is a virus that operates by inserting its own RNA into the cell it attacks, and then producing DNA from this RNA. Antiretroviral drugs that fight HIV usually consist of a combination of three drugs. This is necessary because the HIV virus is very adept at evolving to become resistant to drugs. Taking three drugs at once makes it very difficult for the virus to evolve resistance, as it would have to develop resistance to all three! This method has proven an effective way to suppress the HIV virus, and is now the standard of care for HIV patients.[7]

ART, like most drugs, has its limitations.  “ART is chronic therapy, meaning that it must be taken for life. It is also costly and requires strict compliance. It is also associated with some health problems from chronic chemoexposure.” [1] One of the biggest problems facing HIV treatments today is not necessarily the development of new treatments but the implementation of current ART.  Current estimates are that the nonadherence rate to ART is about 50-70%. This means that the majority of HIV patients do not take ART exactly as they are supposed to.  They could, for example, not be taking the doses at the appropriate time or they could be missing doses entirely.  This is particularly alarming considering that adherence rates under 80% are associated with a detectable amount of HIV in their bloodstream. [2]

This low adherence can be attributed to a variety of factors.  Many patients have trouble remembering to take their pills on schedule, or do not have easy access to refills.  Many HIV patients are low income and may not have permanent housing, resulting in erratic schedules and difficulty in establishing a routine that includes regularly remembering to take their treatment. The prevalence of homelessness among the HIV positive population exemplifies this. The National Coalition for the Homeless estimates that 50% of people with HIV are at risk of becoming homeless.[5] Homelessness makes it very difficult to adhere to ART treatments, as the homeless have minimal access to basic necessities and healthcare.

Because of the difficulties associated with ART, many researchers are still seeking a cure for HIV. Wender discussed this in his interview:

As indicated above, while we are only starting to see clinical studies on these eradication strategies, the next goal would be to eradicate the disease. This would avoid the cost of chronic therapy. It would avoid compliance problems. It would avoid health risks associated with chronic chemoexposure. Moreover it would allow most who either do not have access to ART or are non-compliant to possibly undergo short term treatment that would render them virus free.[1]

Finding a cure to HIV has proven challenging as it rapidly evolves via genetic mutation to become resistant to drugs.  Wender describes it as a “moving target.” [1]

 

Beyond ART

Researchers are employing a variety of unique methods to combat HIV.  One promising new method that has recently been studied is byrostatins.  Byrostatins are a class of molecules that have been found to be promising in treatments for a variety of illnesses.[6] A 2012 Nature Article details how scientists used byrostatin to target latent HIV reservoirs.  Latent viral reservoirs are HIV infected cells that are not actually producing HIV.  They can, however, “wake up” and start producing HIV.  ART does not target these reservoirs.8 Byrostatin could be a promising way to eliminate these reservoirs, which could lead to the elimination of the virus entirely.[6]

The promising nature of byrostatins proves to be just one example of how researchers are continuing to invent new and creative methods to target HIV.  Although HIV has proved challenging in innumerable ways, researchers like Dr. Wender reveal that there is hope for a cure as new and innovative treatments are being developed.

 

 

  1.  Wender, P., P.h.D. (2017 January 29). [Personal Email Interview]
  2. Chesney, Margaret A. “Factors Affecting Adherence to Antiretroviral Therapy.” Clinical Infectious Diseases | Oxford Academic. Oxford University Press, 01 June 2000. Retrieved 11 Feb. 2017 from https://academic.oup.com/cid/article/30/Supplement_2/S171/373130/Factors-Affecting-Adherence-to-Antiretroviral
  3. “A Timeline of HIV/AIDS.” Welcome to AIDS.gov. Retrieved on 11 Feb. 2017 from  https://www.aids.gov/hiv-aids-basics/hiv-aids-101/aids-timeline/#year-1981
  4. “Longer Life Expectancy for HIV-positive People in North America.” CATIE – Canada’s Source for HIV and Hepatitis C Information. Retrieved on 11 Feb. 2017 from http://www.catie.ca/en/treatmentupdate/treatmentupdate-200/anti-hiv-agents/longer-life-expectancy-hiv-positive-people-north
  5. “HIV/AIDS and Homelessness.” National Coalition for the Homeless. Retrieved on 11 Feb. 2017 from http://www.nationalhomeless.org/factsheets/hiv.html
  6. Brian A. DeChristopher, Brian A. Loy, Matthew D. Marsden, Adam J. Schrier, Jerome A. Zack and Paul A. Wender. 2015. Nature, Chemistry. Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro. Retrieved February 11 2017.
  7. “Antiretroviral Therapy.” WHO. World Health Organization.  Retrieved 17 Feb. 2017 from  http://www.who.int/topics/antiretroviral_therapy/en/
  8. “What is a Latent HIV Reservoir” Understanding HIV/AIDS. National Institutes of Health. Retrieved 17 February 2017 from https://aidsinfo.nih.gov/education-materials/fact-sheets/19/93/

Cover image: “Pills” by Jamie is licensed under CC BY 2.0.