• Treatment Interruptions
  Authored by Patrick Yeni (Paris, France)
  Abstract PL1.4

Background

Structured treatment interruptions are popular among certain patient groups. Structured treatment interruptions may be used in three situations. First, to allow a patient with a good immune response a respite from the possible toxicity and adherence problems of an antiretroviral regimen. Secondly, to allow auto-vaccination of individuals in order to maintain suppression of their virus without drugs, and thirdly, in patients who are failing therapy, in the hope that removal of the drug pressure will lead the resistant virus to return to wild-type virus with increased response to a new therapy.

Results

Dr. Yeni introduced the subject of treatment interruptions with a discussion concerning the state of antiretroviral treatment, which he noted is still far from ideal. Clearly, the perfect drug would work in 100 percent of patients, be easy to adhere to and have no toxicities. This, unfortunately, is not the case with HAART. Due to tolerability and adherence problems, many individuals will interrupt their therapy in an unstructured way, and this can lead to problems secondary to the development of resistance.

The idea that a planned structured treatment interruption could have advantages has been around for many years. The theory behind this is that by regularly stopping drugs and taking a break, a patient's exposure to the drugs will be lowered and the chance of developing side effects and toxicities will also be lessened.

In addition, it has been suggested that by stopping the drugs and allowing the immune system a chance "to see the virus" as it rebounds could lead to natural control of HIV in the long term. However, so far this has not been shown to be the case in the clinical setting. Dr. Yeni pointed out the problems of structured treatment interruptions in such a situation, especially in patients who have low CD4 counts. In addition, some patients have had very dramatic falls in their CD4 counts after only a short time off therapy, and some patients even develop a seroconversion-like illness secondary to viral rebound.

In the setting of acute infection, animal studies have suggested that structured treatment interruptions immediately after infection may lead to control of HIV infection. Although there are case reports of this occurring in clinical practice, no data has been presented from a clinical trial of such a situation.

The final situation in which a structured treatment interruption is used is in patients with multi-resistant virus with little chance of rescue with available drugs. Structured treatment interruption in such a position will remove drug pressure for the virus to have continuing resistance and, hopefully, will lead to a better response when drugs are introduced. This is the subject of many ongoing clinical studies, such as the MRC Optima study.

However, in clinical studies, there is little data to support this, apart from the French GIGA HAART study in which patients who had been on failing regimens underwent an eight-week structured treatment interruption, and were then treated with a multiple-drug therapy, had a better response than those who switched directly to multiple-drug therapy. These results were maintained out to 48 weeks. The danger of a structured interruption in such a setting is the possible fall in CD4 count, which may take several months to recover, despite the introduction of antiretroviral therapy, and the increased viral load, which has been noted to be a factor of disease progression in many studies.

Implications for Clinical Practice

Dr. Yeni concluded that the only place for structured treatment interruptions at present is in the context of clinical trial. Many patients may opt for an unstructured treatment interruption, and the dangers of this must be made clear to all patients, so that doctors and physicians can together decide on the pros and cons of a structured treatment interruption.