Ask the Doc: Stopping Rx and the Reservoir

We hear this week from Dr. Paul Bellman, who has been on the front lines of the AIDS epidemic since 1981, and is now in private practice in NYC, and affiliated with the New York Presbyterian Hospital and Cornell Weill Medical College. Dr. Bellman looks at the HIV viral reservoir, and stopping Rx.

Q: What is the HIV viral reservoir? Why is that important?

A: The viral reservoir consists of cells including CD4 cells -- but not necessarily just CD4 cells -- that remain infected with HIV even with highly effective drug cocktails that reduce the HIV level to undetectable levels in the blood. Unfortunately, in almost all cases when the cocktail is stopped there is enough virus still present to produce a rapidly escalating viral load and associated immune compromise.

It had been hoped that HIV patients might be able at the least to take breaks from their medication and possibly reduce the toxicity from what currently in the absence of a cure is ongoing therapy.

However, a large clinical trial both confirmed the inevitably of viral rebound and thus the existence of the reservoirs as well as showed an adverse health risk associated with stopping treatment. Thus, in the absence of a treatment strategy to prevent viral rebound from the reservoir stopping therapy is strongly discouraged by HIV expert physicians, including myself.

There has been a tremendous amount of scientific research directed at understanding the viral reservoir, including types of cells and tissues within which HIV remains shielded from the cocktail and about how when the cocktail is interrupted, a systemic HIV viral infection is rekindled. It has been said that with effective treatment the residual HIV still in the body is like the embers of a fire that might appear out or almost out. Alas, when therapy is interrupted the embers of HIV are quickly rekindled into roaring flames.

But as we learn more about HIV infection as a whole there is reason to be optimistic that even given the problem of the viral reservoir as an obstacle to cure, strategies might be developed to better confine HIV with the addition of immune-based therapies to antiviral therapies, to allow for some patients to safely stop the cocktail.

Indeed, there is intriguing news from the frontiers of clinical research that this approach is worthy of further study and the financial research support it requires.

Q: But I have heard about some people stopping their drug cocktail and still keeping an undetectable viral load. How is this possible?

A: Recently, Dr. Luis Montaner of the Wistar Institute in Philadelphia reported that in a clinical trial that some patients on the cocktail were able to maintain an undetectable state when the cocktail was stopped by continuing treatment with interferon. Interferon is a long-studied antiviral and immune modulator that has been used successfully to cure some patients of chronic hepatitis B and C infections.

Intriguingly, the patients who maintained an undetectable viral load on interferon in Dr. Montaner's study showed signs of their viral reservoirs diminishing above and beyond that of the cocktail.

While it is doubtful that the weekly interferon shots these patients received for what is now in some patients 48 weeks will lead to a cure, it does suggest that there are other ways of tackling HIV and potentially the reservoir itself.

Last summer at the World International AIDS Conference in Washington, D.C., it was reported by French investigators that a very small proportion of HIV patients treated with the cocktail very soon after contracting HIV were able to safely stop therapy. About 15 percent of these patients maintained undetectable viral loads off the cocktail. Some of these patients are off the cocktail and have been on no other therapy for five years or more. Similarly, some of these patients are showing diminishing sizes of their viral reservoirs sparking the hope that they may be on the road to a durable cure.

As we learn more about these patients, as well as from ongoing and hopefully planned new clinical trials, I believe personally that there is every reason to be optimistic that safe and effective curative treatment strategies will be developed for HIV, the thorny problem of the viral reservoirs notwithstanding.

This hope for a future cure is all the more reason to take advantage of the remarkably safe and effective therapy that exists for HIV today.

Most of the time, if there are a few embers still glowing in a fireplace and one falls asleep on the couch, the fire will still be out in the morning. The good news is that many talented scientists and physicians are physicians and scientists are now seriously engaged in this aspect of HIV research.