At the first World AIDS Day, we only had one drug for treating HIV, which was AZT and it was not a particularly good drug. It had numerous toxicities at the doses used and only had a moderate effect on suppressing the virus. Thirty years later, over thirty-five drugs have been approved for use against HIV. Quite a few of these drugs are no longer used because there are stronger and safer drugs that perform better that we can combine to suppress the HIV virus and restore people’s immune system.
We have also learned a tremendous amount about how this virus causes disease and how it affects all systems of the body. We also have some good medicines that can protect an individual from getting infected. Very importantly, we have made treatment available to the millions of people in Africa, South, and South-East Asia and Latin America who quite simply would have died without programs like PEPFAR (President’s Emergency Plan for AIDS Relief) that continue to provide them with free treatment. I am very thankful to have worked with PEPFAR and had an opportunity to contribute my experience and knowledge to this program by improving clinical care and building infrastructure for research in Africa.
Now, as a result of decades of intensive research, both in laboratories and in clinics, a young person being infected with HIV can potentially live almost a normal lifespan. So with all these good things happening, is it still important for us to find a cure for HIV infection? As good as the medicines are, they do not cure HIV and as it stands now, people must take these medications their entire lives. So one thing that must be understood isthat providing HIV treatment for over 37 million people in the world (less than one and a half million are in the US) is NOT economically sustainable!
Most countries in Africa, South-East Asia, Eastern Europe, Latin America, and the Caribbean simply cannot afford to provide medicines for the people in their countries that are infected. Most infected individuals cannot afford to pay for HIV treatment. When you further consider that in many countries (including the US), a significant proportion of HIV patients are not taking their medicines and are not suppressed, new infections continue and expand the numbers in need of treatment. Prevention campaigns have not stopped new infections. We need a cure! But this virus is very clever and there are reasons we haven’t been able to cure it.
In the previous article on the immune system and HIV, I presented some reasons why the immune system doesn’t simply eliminate the virus. It is through the immune system that curable viral infections are eliminated (e.g. flu, cold, mononucleosis, chicken pox). We will review some of the reasons why HIV isn’t cured by the treatment, BUT there are some exceptions!
Elite Controllers
There is a small group of individuals who get infected by HIV yet don’t develop the disease. They appear to effectively control the infection where they don’t experience a decline in their T-lymphocytes, which are destroyed by HIV, and they may have no detectable virus in the blood.
They can remain in this state for years without ever having taken medicines. There are small amounts of HIV in the body that can be detected with special sensitive tests, but it appears their immune systems can keep it under control. These patients are called Long-Term Non-Progressors (LTNP) or Elite Controllers, reflecting the fact that they don’t experience HIV disease progression and are able to control the virus.
When I was working at Johns Hopkins School of Medicine 10 years ago, I found two of these patients in a community clinic. I referred them to my colleague, Dr. Joel Blankson, an African-American physician-scientist working at Hopkins and one of the leading experts on HIV Elite Controllers.
Post-Treatment Controllers
In the previous article, I introduced the concept of the functional cure. A functional cure means that the person’s immune system is controlling the virus without any treatment. There could possibly be a virus hiding somewhere in the body, but it is not able to cause much damage. There are patients who have been treated with HIV medicines and after the medicines suppress the virus to an undetectable level, the patients stop taking medicines and remain suppressed or undetectable.
This phenomenon is not that unusual. It is referred to as Post-treatment control. It is most commonly seen when patients are started very early (within a few weeks to months after infection) on strong combinations of HIV medicines. The reason we think it happens more commonly with very early treatments is (1) The virus has not caused as much damage to the immune system as occurs in someone infected for a longer duration without treatment and (2) there is less virus in certain hiding places in the body where the HIV medicines may not get to as easily.
These hiding places are called reservoirs. I remember seeing a patient around 2006 who might be termed as a functional cure. She was diagnosed a few weeks after being infected and was immediately started on a powerful combination regimen including a protease inhibitor. She was soon undetectable. After about 6 months of being undetectable, her medicines were stopped (not sure exactly why). She remained undetectable. At the time I saw her, she had been undetectable off medicines for about three years.
At the HIV Cure conference held at the NIH in Bethesda MD in October 2018, some interesting findings were presented from the CHAMP study (Control of HIV After Antiretroviral Medication Pause). The purpose of the study was to determine how common post-treatment controllers are and what are the factors that lead to this level of control. Because Post-treatment Controllers are not common, this study recruited subjects from a number of different, separate studies. Patients who were on HIV medicines and undetectable stopped taking their medicines and were monitored frequently.
When virus became detectable in the blood above a certain level, they were started back on medicines. In total. out of more than 700 patients who participated in the study and had their medications stopped, 67 of them remained suppressed. Out of those 67 successes, 38 had started treatment very early afterinfection. The average amount of time patients were on treatment before stopping was about 4 years, but for some, treatment was just over one year.
Factors that predicted the ability to control the virus off medicines include starting treatment early after infection, having much smaller amounts of virus in reservoirs and having less inflammation when the medicines are stopped. Overall, about 55% of the controllers remained suppressed for up to 2 years and going out for 5 years, 20% were still suppressed (about 13 of the original 67). So this study seems to indicate that a small number of post-treatment controllers may achieve a functional cure.
So in summary, some people have the ability to control HIV infection without medication. Elite Controllers can do it all by themselves. Post-treatment controllers can do it after they have achieved suppression from HIV medicines for a period of time. Controlling HIV infection and reducing the complications from the infection without the use of medicines is termed a functional cure.
A better understanding of how these two groups are able to control HIV can possibly lead to better treatment and cure for more individuals. DO NOT STOP YOUR MEDICINES unless you are working with an experienced HIV medical provider or participating in an approved clinical study.
Hopefully, by next World AIDS Day, I will have some exciting news to report in our efforts to cure HIV infection.
He is currently working in the Division of AIDS in the National Institutes of Health. He has published research in the leading infectious diseases journals and serves on the Editorial Board of the journal AIDS. Any views and perspectives in his articles on blackdoctor.org are not representative of any agency or organization but a reflection of his personal views.