Treatment interruption consequences unknown
Drug holidays. Pulsed therapy. Structured treatment interruptions. What are these strange new concepts?
What happened to the days of perfect adherence and pharmaceutical product slogans such as "Every dose. Every day"?
Many top HIV researchers have begun to closely examine the concept of structured treatment interruption (STI). STI is a planned discontinuation of therapy for a pre-determined period of time (usually two months) or until such time as CD4 cells levels decline to a pre-determined level.
Preliminary information was released by Veronica Miller, M.D. and colleagues of Frankfurt, Germany, at the 2nd International Workshop on Salvage Therapies (August Positive Living). This theoretical treatment approach has sparked interest on the part of many.
Miller presented information on 39 heavily drug-experienced patients who were given a "drug holiday" or "treatment interruption" before initiating various multi-drug salvage therapies. By doing genotypic analyses (resistance testing) of each patient's virus after the "drug holiday," but prior to starting antiretrovirals, researchers found that the virus of 26 of the 39 individuals had once again become sensitive to all approved medications. This "reversion to wild-type virus," as it is called, was completely unexpected, as at baseline, all 39 people had genotypic resistance to a median of eight drugs.
Following the new multi-drug regimen, 18 people with the newly drug-sensitive virus achieved viral load levels below 500 copies/ml, compared to only two patients who did not experience a reversion to wild-type virus.
The results from Frankfurt led to a meeting organized by FAIR, Project Inform and TAG, held in July in Boston. Attending this meeting were about 50 HIV researchers from around the world who are directly involved with STI studies designed to enhance viral suppression or regenerate the ability of the immune system to recognize and fight HIV infection.
The meeting identified three main goals:
The meeting began with overviews of the Frankfurt data regarding the return to "wild-type" of multi-drug resistant virus. A brief discussion of additional data from STI studies that have been conducted since May laid the foundation for the discussions to follow.
Solving the issues raised in the three points above was not the intent of this meeting. Working in a creative and supportive "think tank" environment, researchers shared ideas, reviewed study data and explored clinical trial designs.
Another goal was to determine the safety of these approaches and to see whether any particular markers, such as CD4 cell count or viral load level, might predict the potential for success or failure.
Why the interest now?
Interest in "drug holidays" in recent months has been growing for varying reasons.
In the medical community, some believe that (1) viral replication after STI may stimulate an anti-HIV immune response which could help to keep the virus in check and that (2) some HIV-infected people, particularly those in late stage disease, may not have any capacity to mount or maintain an anti-HIV immune response without STI.
However, there is much more to the issue of STI than just the reversion to wild-type virus or the regeneration of an HIV-specific immune response. A more relevant question is, will STI enable people with HIV to tolerate antiretrovirals for longer periods of time with fewer toxicities and greater quality of life?
While those in attendance did not tackle all of the issues related to STI, tangible outcomes from this meeting were seen. For example, a subcomittee of those attending the meeting will develop a protocol for STI for physicians who wish to initiate this approach in their patients. In developing this protocol, patient safety will be the primary concern of the committee.
More meetings on STI and at least 12 clinical trials addressing STI issues are planned, including four trials in the L.A. area. These trials will mostly examine the use of STI in people who are in need of salvage therapy or who have detectable but stable viral load levels. These trials are not advisable for people who, for reasons of convenience, want to stop their current therapy.
Speculation not confirmed
Some researchers, particularly those at the Aaron Diamond AIDS Institute in New York, believe that STI may be very dangerous for people with undetectable levels of HIV. The theory, which is not proven, is that viral reservoirs or sanctuaries that may have been cleared of virus could be "re-seeded." Viral reservoirs are protected places in the body (testes, ovaries) where HIV can replicate despite potent antiretroviral therapy.
If this theory is true, and eradication is still a possibility, treating HIV could be significantly complicated by STI.
The bottom line: STI is highly theoretical research that should not be considered lightly. People should not take drug holidays or initiate STI on their own without their physician's supervision or direction.
This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).
This article was provided by AIDS Project Los Angeles. It is a part of the publication Positive Living.