Follow-up Data From Studies of Intermittent Therapy and Treatment Interruption
August 8, 2000
A growing awareness of the difficulties -- such as short- and long-term side effects, high costs, and adherence issues -- of continuous antiretroviral therapy (ART) has led many researchers to explore the safety and effectiveness of alternating between periods on and off therapy. Data was presented at the conference from studies designed to investigate two new similar approaches known as structured intermittent therapy (SIT) and structured treatment interruption (STI). Both strategies seek to limit the time on ART, while still maintaining low viral loads. Researchers are hoping there may be a return of the natural HIV-specific immunity that is lost during HIV infection, due to repeated exposure to low levels of the virus during the periods off therapy.
The largest study of STI to date is known as the Swiss-Spanish Interruption Study. Data presented at the conference was for 122 participants, out to 36 weeks. Each person studied was on a protease inhibitor-containing regimen and had a viral load below 50 copies before beginning this treatment interruption trial. The cycle of treatment was then two weeks off medications followed by eight weeks back on medications. It had been hoped that this strategy would stimulate the immune system enough to lower the amount by which the viral load rose, or rebounded, during the periods off of therapy. On average, however, the viral load came up to about 1,000 copies during each of the periods off of therapy, and this number did not decline during subsequent cycles. In addition, approximately 5% of the participants' viral loads did not return to below 50 copies after each two-week interruption in therapy. These results indicate that STI was not a successful strategy for the majority of individuals.
Building on the study of STIs was a concept introduced in a presentation by researchers from the U.S. National Institute of Allergy and Infectious Diseases (NIAID). Structured intermittent therapy (SIT) is being explored as another alternative to long-term, continuous ART. The NIAID is currently studying SIT with two different intervals of on/off therapy: two months on/one month off and one week on/one week off. Extremely preliminary data was presented from each branch of the study. In the two months on/one month off group, six out of seven people saw a trend toward lower viral loads during successive periods off therapy. It also seemed that immune health could be maintained during the periods off therapy: total CD4+ and CD8+ cell counts did not change over the four to nine months the people were observed. Out of seven people in the one week on/one week off cycle, six saw no detectable viral load and one saw a spike above the level of detection.
The discouraging results from the STI study and the preliminary nature of the SIT study data led most presenters to caution HIV-positive individuals and their providers against the use of these strategies outside of closely monitored clinical trials. The possible drawbacks of both SIT and STI were also discussed. One concern is that cycling on and off therapies may create resistance to antiviral medications. Another question that needs to be addressed is whether or not people using structured interruptions or intermittent therapy stay as healthy, clinically, as those who are on continuous ART.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Ezine.