Experts Sound a Cautious Note
By Bruce Mirken
AIDS Treatment News #346
Interest in what has become known as structured (or strategic) treatment interruption (STI) is high among people with HIV, judging from attendance at an April 17 community forum sponsored by Project Inform and Survive AIDS (formerly ACT UP Golden Gate). Project Inform's outreach coordinator counted 120 people in attendance, the largest turnout at any PI forum in San Francisco for some time.
Many are clearly weary of taking difficult drug regimens that can have serious toxicities. As Steven Deeks, M.D., a University of California San Francisco researcher and clinician who has been studying treatment interruption, put it, "There have been people in the community dying to stop these drugs."
But Dr. Deeks and the other members of the panel--fellow UCSF researcher Jeffrey Harris, M.D., Ph.D., and treatment activists Ben Cheng and Martin Delaney of Project Inform and Matt Sharp of Survive AIDS, urged a cautious approach. Most research so far, they noted, has been in the form of small pilot studies that have given intriguing hints but no definitive answers as to whether STIs are beneficial or how best to do them. All agreed that patients who choose to attempt STIs on their own need to work closely with their physician and be carefully monitored.
STI After Drug Failure
Deeks discussed his data from an observational cohort of 400 patients at San Francisco General Hospital using protease inhibitor-based regimens and experiencing virologic failure, defined as a detectable viral load of over 500 copies. He noted that these patients still maintained most of their gain in CD4 cells despite a partial loss of control of the virus.
But Deeks noted that in a recent conference presentation, Veronica Miller, the German researcher whose report of this reversion to wild type helped generate interest in STI, reported that when patients went back on treatment, "the viral load went down to undetectable, but in general came back up. The question is, was the risk worth it? Because there was significant risk: These people typically lost 100 to 150 T-cells, which is a lot of T-cells, and they did not come back that quickly. She said that they came back after a year."
Thus, the ultimate effect of STI in treatment-experienced patients with resistant virus is unclear. "As far as we can tell, if you do not stop therapy you keep those T-cells," Deeks noted, "so it's a complicated issue right now." Further studies, just getting underway, may improve our understanding.
Deeks described his own work which suggests why continued therapy seems to have some benefit even if virus remains detectable. In 25 patients who stopped therapy, Deeks and colleagues performed weekly resistance tests on their virus and found that after a few weeks (the exact time varied from patient to patient), the resistant virus disappeared suddenly and almost completely, replaced by wild type. It was at the same time that wild-type virus reemerged, he noted, that viral load "shot up" and T-cells plunged, suggesting that wild-type virus is "more fit" and able to do more damage. Patients may benefit because treatment forces their virus to mutate into less virulent forms.
STI to Stimulate Anti-HIV Immune Response
A very different rationale for strategic treatment interruption is the possibility that patients maintaining undetectable virus can take breaks in treatment, allowing a brief burst of viral activity that will boost their anti-HIV cellular immune responses. This might, at least in theory, create a vaccine-like effect that improves control of HIV, while allowing patients to take a rest from unpleasant drug regimens.
Dr. Harris described a study he is now beginning at San Francisco General Hospital that will test this notion in patients who have been on therapy for at least 12 weeks with an undetectable viral load. Harris has recently begun enrolling participants, who will be monitored closely. Interested persons can call 415-695-3820 for more information about this study.
No one on the panel felt comfortable recommending STIs based on the current data. Deeks offered this general advice: "If it ain't broke, don't fix it. If you are tolerating your meds, I wouldn't mess with it."
For those experiencing serious toxicities or otherwise wanting to take a break from treatment, the panel urged close consultation with one's health care provider. Cheng noted that regimens involving nonnucleoside reverse transcriptase inhibitors (NNRTIs)--nevirapine, delavirdine and efavirenz-- present an extra complication because these drugs linger in the blood longer than other anti-HIV drugs. This could allow the development of resistance if all drugs are stopped simultaneously, so it may be advisable to stop the NNRTI first.
Deeks advised frequent monitoring of CD4 and viral load levels, at least every two weeks at the beginning of an STI. This may be particularly important, he suggested, for those who had very low CD4 counts prior to starting therapy, as these individuals may be most likely to see their CD4 counts drop back down to a level at which prophylaxis for opportunistic infections is needed.
Most in the audience seemed to find the discussion informative and worthwhile, despite one frightening interruption: About 40 minutes into the presentation a dozen members of ACT UP San Francisco--a renegade chapter disowned by other ACT UP groups and aligned with the AIDS denialist movement--stormed into the room and threw handfuls of pills at Delaney and other panelists, shouting, "You're a liar!" and "Murderer!" Several minor scuffles broke out as disgusted audience members chanted "Shut up and leave!" at the invaders.
A Project Inform staff member was injured in the fracas and was taken to a nearby hospital with bruises and a painfully swollen knee. She and several others who were roughed up filed police reports and expressed their intent to press criminal charges. After about 10 minutes the disrupters left, and the meeting continued without incident. Despite the violence, nearly the entire audience remained to hear the full discussion.
[Note: For a detailed account of the disruption, see "More Violence from ACT UP/SF: Woman Injured at HIV Treatment Forum," in the Bay Area Reporter, a San Francisco gay newspaper, April 20, 2000, page 1.]
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