43rd ICAAC: Structured Treatment Interruption--The BASTA Study

Date of Report: 10/08/2003
Author:  Susa Coffey, MD
Source: AETC National Resource Center

The BASTA study examined the effect of planned treatment interruption in patients with successful and sustained responses to antiretroviral therapy with the intention of decreasing exposure to antiretroviral medications.

Individualized Structured Treatment Interruptions: Results of a Randomized, Controlled Study (BASTA). Maggiolo F, Ripamonti D, Gregis G, Quinzan G, Arici C, Ravasio L, Callegaro A, Suter F. 43rd ICAAC, Chicago, September 2003. Abstract H-448.

Description

In this study, 114 patients on antiretroviral therapy (ART) with HIV viral loads <50 copies/mL and sustained CD4 levels >800 cells/mm³ were randomized 2:1 to undergo structured treatment interruptions (STI) or to continue their usual treatment. Treatment was restarted if the CD4 level dropped below 400 cells/mm³, and interrupted again if the CD4 rose to >800 cells/mm³. The primary endpoint was the proportion of patients with CD4 >400 cells/mm³ at predetermined time points. Secondary outcomes included time off ART and predictors of sustained treatment interruption. Patients were well matched for baseline characteristics, and had median baseline CD4 of nearly 1100 cells/mm³ and nadir CD4 of 392 cells/mm³ (STI group) and 334 cells/mm³ (control group). Analysis was by intent-to-treat methodology.

Results

By 18 months, 21% of STI subjects had a decline in CD4 count to the predetermined threshold of <400 cells/mm³ and were restarted on treatment (one subject twice). STI patients with higher nadir CD4 levels remained on treatment interruption for longer periods than did those with low nadir CD4:

Overall, STI patients spent 12% (mean) of the study time on antiretroviral therapy. In STI patients who restarted treatment, CD4 counts rose quickly. By multivariate analysis, nadir CD4 was the only independent predictor of CD4 decline and therefore of reinitiation of treatment.

The STI group showed significant improvements in cholesterol and triglyceride levels, as well as impressive overall reductions in the cost of patient management, as compared with the control group. Two patients experienced symptoms of the acute retroviral syndrome during treatment interruption. Two STI patients withdrew from the study because of adverse events (cytopenias), while eight in the control group discontinued therapy (six by personal choice, one for virologic failure, one for an adverse event).

This study is ongoing.

Conclusion

This study suggests that in patients with high pre-treatment CD4 levels, and in some patients with robust and sustained responses to antiretroviral therapy, treatment interruption may be safe, and may confer advantages in reduction of overall drug exposure, improved metabolic parameters, and decreased costs.

The SMART study, a large, multicenter randomized STI trial conducted by the Community Programs for Clinical Research on AIDS (CPCRA), is currently underway. Although its protocol differs from BASTA in several important respects, SMART also examines the effects of stopping and starting treatment based on CD4 thresholds, and should provide a more comprehensive assessment of the issues involved in this approach to HIV treatment.