Objective: To compare continuous highly active antiretroviral therapy with a CD4 cell count-driven structured treatment interruption (STI) strategy. The primary end-point was the proportion of subjects maintaining CD4 cell count > 400 × 106 cells/l. Secondary end-points were to identify the dynamic and predictive variables of CD4 cell loss.
Methods: The BASTA study is a randomized, controlled, prospective trial. Patients with CD4 cell counts > 800 × 106 cells/l were enrolled and the immunological threshold to resume therapy was set to the lower normal limit of CD4 cells for HIV-uninfected adults.
Results: Sixty-nine patients were randomized and followed for 64 weeks. At baseline, all had undetectable plasma HIV RNA and their mean CD4 cell count was 1077 × 106 cells/l. None of the patients showed a disease progression or any AIDS-defining event. At each time point, the proportion of subjects in the STI group that had a CD4 cell count < 400 × 106 cells/l was not statistically different from the control group. In all cases, the 95% confidence interval for this difference was smaller than ±10%. However, 57% of patients with nadir CD4 cell count 200–350 × 106 cells/l reached a CD4 cell count < 400 × 106 cells/l. This was statistically different (P = 0.02) from the nearly 90% of patients with a nadir CD4 cell count 350–500 × 106 cells/l who maintained a CD4 cell count of > 400 × 106 cells/l.
Conclusions: Prolonged STI in patients with fully suppressed virus and marked immune reconstitution is generally safe. The main predictor of CD4 cell decline is the nadir CD4 cell count. Pulse therapy warrants further careful prospective evaluation to investigate virological and clinical outcomes over a very long period.
From the aDivision of Infectious Diseases and the bMicrobiology and Virology Laboratory, Ospedali Riuniti, Bergamo, Italy.
Requests for reprints to: F. Maggiolo, Divisione di Malattie Infettive, Ospedali Riuniti, Largo Barozzi 1, 24128 Bergamo, Italy.
Received: 18 February 2003; revised: 2 July 2003; accepted: 11 August 2003.