By Tim Schacker, M.D.
Here are the facts. There are 35.3 million people on this planet living with HIV and most of these people have limited access to any form of treatment. Every 6 minutes another person is infected with HIV and every 10 minutes someone dies from the disease. In the United States there are 1.1 million people living with HIV and 1 in 6 are unaware of it. Fifty thousand Americans are newly infected every year, a statistic that has not changed in over two decades. In Minnesota, there are approximately 7,000 people living with HIV, but this is probably an underestimate as there are many infected people who have never been tested. Last year there were 301 new HIV infections diagnosed in Minnesota and among those, 1/3 were diagnosed with AIDS at the time they are found to be HIV+. The global, national, and local burden of disease from this infection is staggering.
We have made significant progress in the treatment of HIV. There are new formulations of antiretroviral drugs that have been combined into one pill that can be taken only once a day. These drugs have provided significant clinical benefit with people living longer and living healthier. This is a remarkable achievement as it was not that long ago that a diagnosis of HIV meant you would soon die. However, it is really important to understand that treatment with these drugs is not a cure. HIV infected people on treatment still have a shorter life span, still have abnormal immune systems and are now being diagnosed with infections, cancers and other serious problems that have not been seen before in this population. Moreover, HIV+ people on ART are considered to be aging at a faster rate than someone the same age who is not HIV infected. We are seeing younger people becoming frailer and have an increased rate of heart disease, stroke, and blood clots. Beyond the personal turmoil this infection creates the cost to society is also quite large. The lifelong cost of care for HIV infected people is very expensive (up to $1500/month for medications alone) and the cost for social programs to support this growing population is very large.
This disease is not going away. We can’t cure it and we have no effective vaccines, microbicides, or devices to prevent transmission (except correct and consistent use of condoms and pre- or post-exposure prophylaxis). The natural question to ask today is why. In 2011, the United States federal government spent approximately 3.4 billion dollars on research into HIV and in 2012, 3.5 billion. These investments are yielding important discoveries about how and why the virus causes AIDS, which provides new opportunities for treatment. The National Institutes of Health recently formed 3 large collaborative networks of scientists from all over the world to find the cure for HIV. Two scientists from the University of Minnesota (myself and Dr. Ashley Haase) belong to these “collaboratories” and the ideas and discoveries being made by these groups are amazing. Our goal is to turn these basic science discoveries into novel treatments that may lead to the cure. We are looking at entirely new “out of the box” ways to eradicate infected cells from the body. We are looking at new classes of drugs that might selectively kill cells that have HIV in them, novels ways of making a persons CD4 T cells unable to be infected with HIV using gene therapy, and ways to “train” the immune system to find infected cells and eliminate them. However, progress along these lines is frustratingly slow; scientific discovery often sets its own pace.
Once we have an idea that could turn into a human treatment the progress at testing these ideas in humans is also too slow. We have a complex set of rules and regulations about what we can and can’t do in human studies and legal issues that have to be sorted out before we can start any human trial. But, once a study is up and running, the single biggest barrier to human research is a lack of participants (volunteers). If recruitment goals are not met, a study is shut down and what might have been a great idea that would significantly advance the field becomes a missed opportunity. This has happened many times in human research, across all diseases, not just HIV. Nationally, the rate of participation in human studies is declining. This is not a problem that affects just HIV/AIDS, this is a serious problem in every topic area. Recent data suggests that a total of 21% of people who respond to study advertising show up for a screening visit and of those, 7% enroll into the trial and 5% complete it. If a study needs 500 people to complete the protocol to know if the intervention works, that means 10,000 people have to pick up the phone and express interest in the study.
I remember the activism of the 1980’s and 1990’s that led to major advances in the care of people with HIV/AIDS. Organizations like ACT UP demanded progress and pushed for accelerated approvals of promising therapies. This led the FDA to fast track the approval of antiretroviral therapies that are the reason we saw the rates of death from HIV/AIDS decrease dramatically in the mid-1990s. Human studies filled quickly. That sense of urgency is gone. Perhaps people believe that we have solved the problem of HIV/AIDS but given the number of people infected, the new clinical problems we are facing, and our inability to cure the infection, that is not the case. Part of the complacency may be due to the fact that the place where this disease is most devastating is beyond our borders; we don’t see it as much as we did before. Walking into a clinic in Kampala, Uganda to see a room full people with advanced AIDS and no access to medicines who will soon die from AIDS reminds me of the early days of the epidemic in the US, only on a much larger scale. Today, in 2014, the rate of infection in pregnant women in South Africa is up to 40%. We simply can’t afford to be complacent about this disease.
I believe that we can, and will cure HIV but that it will take the effort of everyone. The Twin Cities has a rich and engaged clinical research community studying HIV/AIDS. There are many opportunities to get involved, even if you are not HIV-infected. Dr. Keith Henry at Hennepin County Medical Center (HCMC) has several studies looking at novel anti-HIV drugs that may become part of first line regimens if they are successful. But we won’t know unless we do the study. Dr. Frank Rhame at Allina is looking at new treatments for Hepatitis C, a common co-infection with HIV that makes HIV harder to treat and accelerates the pace of the disease. Dr. Jason Baker, also at HCMC, is studying the phenomenon of accelerated aging in HIV and looking at novel interventions to slow that down. Our group at the University of Minnesota is trying to understand why we can’t completely restore immune function with ART. We have a study to see if an FDA-approved drug can improve CD4 T cell counts with antiretroviral therapy and help to restore immunity. We are also looking at how we can improve antiretroviral therapy so it is more suppressive. We all need committed, community-minded people to enroll in these studies so that we can advance the field and hopefully provide better options for people living with HIV.
I can give you a recent example of a clinical study that has fundamentally changed the way we think about antiretroviral therapy. We wanted to know why the current drugs do not do a better job of suppressing the virus from replicating and why some people have evidence of ongoing virus replication, despite having an undetectable viral load (a measure of virus in the blood). Fourteen committed volunteers allowed us to measure ART drug levels in cells from their lymph nodes and large intestine (where the virus actually replicates). We wanted to know if the drugs were actually getting to the site where the virus replicates. We found that drug levels are unexpectedly low in those tissues and that the amount of drug we measured correlated to the amount of virus replicating in those tissues (e.g., low drug level in lymph node was associated with more virus replication in that lymph node). In most of the volunteers we found evidence for ongoing, persistent virus replication in these tissue compartments, even though they had an undetectable viral load in their blood. To make that fundamental discovery, which is that the current drugs are not as suppressive as we originally thought, required the dedication and commitment of these volunteers. We now know that our inability to get the drugs into these tissues is a barrier to cure and that we have to fix the problem by first understanding why they don’t get in and then figuring out how to get them in. Several labs have already started working on this, and that is because of those 14 volunteers.
It is important that you get involved. Find out what kind of study you might qualify for. Talk to your doctor about this. Look into options; there are lots of opportunities. Be a part of the cure.