A Husband and Wife Team on the Search for a Cure

IAVI Report caught up with husband and wife team Robert and Janet Siliciano from Johns Hopkins University School of Medicine in Baltimore, Maryland, at this week's Keystone Symposium to get their initial impressions of the meeting and their take on the status of HIV cure research.

This week’s Keystone Symposium in Boston, Mechanisms of HIV Persistence: Implications for a Cure, is featuring research updates on efforts to define, quantify, and eliminate the HIV reservoir (the pool of latent virus that persists in the body even in individuals on suppressive antiretroviral therapy). This reservoir is considered the main obstacle to curing HIV, and no discussion of it would be complete without the husband and wife team Robert and Janet Siliciano from Johns Hopkins University School of Medicine in Baltimore, Maryland, who continue to study the latent HIV reservoir and efforts to combat it.

IAVI Report caught up with this duo of leading researchers in Boston this week to get their initial impressions of the meeting and their take on the status of HIV cure research.

What do you think of what you’re hearing this week?

Janet Siliciano: It’s been very informative. The clinical trial data being presented is very interesting.

Robert Siliciano: It’s good that there’s a whole week dedicated to HIV cure. The whole field is focusing on it.

JS: And the whole field is here. The discussions are showing us some of the problems that we are going to face, and it’s borne out by some of the trial data we’re hearing: about the difficulties in reversing latency and the basic science behind that. Douglas Richman just summarized really nicely what we know and what we don’t know about macrophages and the central nervous system [another HIV hideout]. He hit the nail right on the head.

Did anything surprise you this week or change your thinking about the HIV reservoir?

RS: There’s so much collaboration in the field that we are talking to each other all the time anyway. We’ve heard earlier versions of the things we’re talking about now.

JS: I don’t think there’s been any definitive data presented that there are additional reservoirs. The best-characterized reservoirs are of latently infected CD4+ resting memory T cells. I haven’t seen any data at all that can convince me that there are any other reservoirs. We’ve defined reservoirs as a cell type that persists in patients on suppressive highly active antiretroviral therapy (HAART) for on the order of years.

It’s clear that other cells in other places get infected. Whether these are long-term…latent reservoirs for HIV—there’s been no data presented on that. Not to say we shouldn’t study it; of course we should.

David Margolis just had a report that confirmed the data on the stability of the latent reservoir. Whether patients are treated during acute infection or chronic infection, the reservoir might be smaller, but the range of latently infected cells is about the same. The decay of these latently infected CD4+ resting memory T cells is also the same in adults. It is on the order of years.

RS: Everyone accepts that this is the big issue. The reservoir is so stable that it is never going to go away. You’re going to have to do something to get rid of it.

What did you think of what Francoise Barré-Sinoussi said the other day about remission from HIV being a more feasible goal right now than a sterilizing cure?

JS: That would be the goal, but it’s going to take a combination of things. Millions of people are getting infected with HIV every year. It’s not sustainable. It would be nice to get people off of HAART for a remission period as new people are coming on to HAART. Thirty-five million people are infected [and currently living with HIV]. [The goal is to] come up with some strategy—maybe giving them some kind of therapeutic vaccination (there’s been very good discussion about broadly neutralizing antibodies here in that respect) to boost the host immune response, and then give these patients combinations of latency-reversing agents. As you’ve seen, single agents aren’t doing anything to reduce the latent HIV reservoir. Combinations may. Then take people off of HAART.

You’re going to have to monitor these patients very closely for long periods of time. You’re going to have to wait until they rebound. We really don’t have an accurate measure of the latent reservoir. We don’t know when patients are going to rebound. We know based on modeling that we’re going to have to reduce the reservoir at least three logs in order to get a significant delay in time to rebound once patients come off of HAART. But you’re going to have to follow patients really closely. - Michael Dumiak