Treatment Interruption: Most Patients Could Not Maintain Immune Control

by John S. James

Summary: Some patients treated very early with an experimental protocol (that stopped and restarted antiretroviral treatment when certain conditions were met) were able to stop antiretrovirals entirely and control their viral load without the drugs for at least 90 days. But after two years, only three of fourteen were still able to control the virus without treatment.

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A leading research group on HIV treatment interruption reported that very early antiretroviral treatment with supervised interruptions did not enable most patients to develop enough immune control to stop antiretrovirals permanently. While 11 of 14 patients were able to remain off treatment for as long as 90 days (with viral load under 5,000, an arbitrary level based on the treatment guidelines in use when the study started), only 3 of the 14 could stay off treatment entirely for as long as two years. Seemingly good HIV-specific immune responses were found, but often they were not protective. It is not known if the viral setpoint was lowered in these patients by this early treatment protocol. This research update appeared in the December 2004 issue of PLOS Medicine (a new online journal published by the Public Library of Science), where it is freely available to anyone [1].

Treatment interruption in order to establish immune control should not be confused with other kinds of treatment interruptions, such as the five-days-on-two-days-off reported elsewhere in this issue. That more modest interruption seeks to reduce antiretroviral use in carefully selected patients in order to reduce expense and improve quality of life, not to help the immune system gain permanent control of HIV. Treatment is discontinued for only two days then automatically restarted before the virus has a chance to come back -- not discontinued for years at a time if viral load stays low.

Comment

Our impression is that the early HIV treatment and interruption to help build immune control of the virus probably is helping, but not enough for most patients. Some of the newer research into HIV immunity and pathogenesis may ultimately provide the additional help necessary. We need more research on why some primate species (and a few people) do not get infected with HIV, or do get infected but then do not get sick, and whether some of the mechanisms involved could be produced artificially by drug treatment.

It will be necessary to build public-interest advocacy to make sure that needed research happens, since the companies already selling antiretrovirals may not have an incentive to greatly reduce their use.

References

1. PLOS Medicine. December 2004; volume 1, issue 3: number e70. Open access (no subscription needed) at http://medicine.plosjournals.org/. A search for "interruption HIV" (without the quotes) will find this and related articles in PLOS Medicine.

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