Where we have been and where we are going
When I started my career in the late 1990s, being on HIV medication meant taking a handful of pills (four to six tablets) two to three times a day, along with another handful of pills to control nausea, vomiting, diarrhea and neuropathy. My patients would take these cocktails of pills before a meal, after a meal or “as a meal.”
Many of them did so gladly. The days when an HIV diagnosis was a death sentence were just barely a few years behind us, and those handfuls of pills were a lifeline for a community of people that had been through much sorrow and pain.
But HIV therapy at that time did not work for everyone. Unable to cope with the pill burden and the side effects, many still succumbed to their disease. But with each passing year, new options appeared, and the medications became easier and easier to tolerate.
Today, most people living with HIV can be treated with single daily tablet regimens, a combination of two tablets taken once daily or, increasingly, medications that can be administered by injection every one-to-two months.
How did we transform HIV infection from a disease with a near 100 percent mortality over 10 years to a chronic condition that can be dealt with by taking one or two of pills every day or getting a couple of shots every few months? The answer, in large part, is clinical research.
But what exactly does that mean?
I am a physician and clinical researcher currently working at Prism Health North Texas, and I am going to explain why, as a clinician, I am delighted to be able to advance the science related to the treatment and prevention of HIV infection as part of my practice.
Clinical research is the mechanism by which novel medical therapies are investigated for both efficacy and safety and then, ultimately, made available to people who can benefit from improved therapies. Typically, it involves a partnership that starts with basic scientists, both in industry and academia, doing benchwork to elucidate mechanisms of disease and the discovery of compounds that can affect those mechanisms. Promising compounds are rigorously tested in laboratory conditions and in animals to make sure there is a strong chance that they will be reasonably safe and effective in humans.
Once a promising compound is identified, an IND — or Investigational New Drug application — is submitted to the Food and Drug Administration for review. If the FDA agrees that the compound has a reasonable chance of being safe and effective in humans, clinical research trials are designed.
Clinical research trials are carefully reviewed experiments designed to prove that potential new therapies are indeed safe and effective in the people that need them. Clinical trials are the result of years of planning and execution involving collaboration among pharmaceutical manufacturers, regulatory agencies (such as the FDA), clinical researchers (usually medical doctors, advanced practice nurses and pharmacists), ethics boards and, perhaps most importantly, patients and healthy volunteers.
The time from FDA IND submission to the completion of clinical research trials, which will be used as the evidence that the compound can and should be available to patients, generally takes about two-to-four years.
The clinical trials process culminates in the submission of a massive document, often more than 30,000 pages, to the FDA called a New Drug Application or NDA.
The NDA is reviewed by the FDA staff and submitted to scientific and public scrutiny through advisory boards. These advisory boards make recommendations to the FDA regarding which compounds should or should not be approved.
Once approval status is granted, drugs become available to physicians, nurse practitioners, and physician associates to be used in the treatment of their patients.
In the context of HIV/AIDS, these trials have resulted in the approval of 25 medications that, in combination, suppress HIV viral levels to such low levels, that people living with HIV often achieve a near normal quality of life and a near normal life span as compared to people who are not living with HIV.
While excellent treatment options are available, the reality of our situation is that we have not gone far enough. Statistically, we now predict that if 95 percent of everyone living with HIV knew their status, and if 95 percent of everyone that knew their status were enrolled in care, and if 95 percent of everyone enrolled in care maintained an undetectable viral load, then the number of people with living with HIV would begin to drop, and the disease could eventually be eliminated.
Sadly, very few regions in the world are meeting these goals, and the DFW metroplex is not one of those.
Part of what is needed to achieve the above mentioned 95/95/95 goals are enhancements in our care delivery systems that make accessing HIV medications more convenient, affordable and livable for the people affected by this disease. Various agencies of the Federal Health Resources Services Administration generally address this through a type of clinical research called “Demonstration Projects.”
But improvements in the medications themselves are also much needed.
Over the past few years, I have learned from my patients that for many the burden of taking a daily oral reminder of their HIV status often elicits anxiety, fear and, in some cases, painful flashbacks involving traumatic events. The advent of new injectable treatments has been as much of a lifeline for some of my patients as the original handful of pills were during the 1990s. The only way to continue to make advancements is through the clinical research trial process.
At Prism Health North Texas, we are currently investigating new compounds that will offer new single tablet daily regimens that lack some of the side effects associated with current medicines, new once weekly oral regimens, injectable medicines that can be given every three-to-six months and some promising strategies that will hopefully lead to cure allowing people living with HIV to maintain their health without ongoing treatment. We also have a pre-exposure prophylaxis (PrEP) trial that is looking at a new oral medication taken once monthly.
If you would like to learn more about clinical trials ongoing at Prism Health North Texas, you can contact me at Prism Health North Texas.