The "Mississippi child," the "Boston patients," the individuals observed in the VISCONTI cohort, and a certain French teenager have all sparked intense interest in the phenomenon of "post-treatment control" of HIV. But all those individuals started treatment relatively early in their HIV infection. What about people whose bodies are able to keep the virus in control for a period of time after stopping therapy, despite having initiated treatment during chronic infection? And what can be learned from this miniscule minority of people living with HIV?
Matthew Perkins, M.D., an infectious disease fellow at Walter Reade National Military Medical Center in Bethesda, Maryland, is engaged in the first study of such individuals, using data from the U.S. Military Natural History Study. I spoke with Dr. Perkins about his study, and next steps for this exciting research, at ID Week 2015 in San Diego, Calif.
Welcome, Dr. Perkins. What are post-treatment controllers and why are they important to study?
Post-treatment controllers are people who are HIV infected, are on antiretroviral therapy for a period of time, and then, for one reason or another, stop therapy -- for personal reasons, or perhaps they were being treated for some other medical condition. A very small percentage of these people are actually able to continue to control their HIV infection, even off of antiretroviral therapy.
Obviously, this is very exciting. In most of the studies that have looked at this, most of the patients have been people that were started on ART [antiretroviral treatment] during their acute HIV infection. We are the first to report people who are chronically HIV infected, who have been infected for a number of years before starting on ART -- which is the majority of people -- who stopped their therapy for one reason or another and yet were able to control their infection off of medication for a period of time.
One of them never redeveloped significant viremia. He went back on medication when he desired to conceive a child with his partner. The other three did eventually go on to redevelop viremia, and needed to go back on ART, but had varying degrees of spontaneous control off of therapy, ranging from nine months, up to almost three years.
When you say "spontaneous control" off of therapy: Were there periods of viremia followed by "self-control" -- if that's one way to put it?
There were some blips, in terms of detectable viral load. Our set point that we defined as being controlled was less than 400 copies. The reason why we used that set point is that our data go all the way back to 1986. With some of the older methods of looking at viral load, that was the cut-off. They couldn't detect anything lower than 400, so that's what we chose as our definition of controlled infection.
But all of these patients did have less than 400 copies detectable, ranging from nine months up to three years; and, as I said, one of whom never redeveloped significant viremia, but went back on therapy for other reasons.
And this is a very small percentage of the overall sample that you looked at?
Yes, a very small percentage. We started out with basically 4,700 patients who had HIV, who had been on ART at some point. We then excluded people for whom we didn't have a record of a viral load of greater than 1,000 copies prior to starting ART. We also excluded people for whom we didn't have clear documentation of control of their infection -- suppression of viral load between six months and two years after starting ART.
Then we looked for people who had stopped ART for some reason and had a viral load checked at least 30 days after stopping therapy. We identified 85 people who fit that. Among those 85, we identified these four who had some period of time of control of their infection.
Talk a little bit about recent developments in the field that led you to look into this phenomenon.
The main thing that led us to look into it was just the fact that other people have reported these patients who are able to control their infection off of ART. I think, in terms of advances, this is very important in terms of thinking about a functional cure for HIV.
We know that the reservoir is very difficult to eliminate. These patients who control their infection off of ART: You can still find HIV proviral DNA in circulating white blood cells, things like that. But they are able to control the infection. In terms of thinking about advances in HIV, that's where this is very important: looking and seeing if these people have some sort of immunogenetic characteristics that allow them to control; and maybe even something that we could induce in people.
The next big step for us is that we do have serum samples on hand. We want to analyze those samples to look at some genetic characteristics -- like HLA subtypes -- and then we also want to analyze the white blood cells and see what their reservoir is: Did they have a low reservoir?
That would be very interesting, considering the fact that all these patients were started on antiretroviral therapy during chronic infection, after they had been infected for a period of time. So the next step for us is to do more analysis of the blood from these patients.
What's the significance of your sample having been drawn from a military cohort of patients?
I think the main significance is that it's very well characterized. Some of these people were active duty while we were following them. They kind of have to come to their appointments; so we have very good follow-up. We have repeated blood samples that were obtained.
There is also the fact that their antiretroviral therapy is covered by the military, so they're able to be treated. I think those are probably some of the significant aspects of a military cohort.
It also seems as if it was possible to have consistent medical records dating back a long period of time, which makes a study like this possible.
Oh, yes. We have excellent documentation of their medical records.
This transcript has been lightly edited for clarity.