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Staccato Trial Supports CD4-Guided Treatment Interruption

However, most subjects were receiving ritonavir-boosted saquinavir-based therapy.

CD4-guided interruption of potent combination antiretroviral therapy was the focus of several trials presented at the 2006 Retrovirus Conference (ACC Mar 15 2006). Now, published findings are available from the two completed arms of the Staccato trial. The other arm, testing week-on/week-off therapy, was stopped because of unacceptably high rates of virologic failure (ACC Dec 1 2003).

The current report focuses on 430 patients with on-treatment CD4 counts >350 cells/mm³ and viral loads <50 copies/mL who were randomized to continuous therapy (146 patients) or treatment interruption (TI; 284 patients). TI involved stopping therapy at enrollment until a patient’s CD4 count fell below 350 cells/mm³ and then restarting it for at least 12 weeks, with another interruption when the CD4 count rose above 350 cells/ mm³. A total of 346 subjects from Thailand were using ritonavir-boosted saquinavir-based therapy; the other 84 were using a variety of antiretroviral regimens. Patients in the TI group who had been on NNRTI-based therapy had the NNRTI stopped 1 week before the other drugs in the regimen.

Mean follow-up was 1.7 years, with the entire TI group having spent at least 12 weeks of the study on antiretroviral therapy. By study’s end, the percentage of patients with viral loads <50 copies/mL was similar in the TI (90.5%) and continuous-therapy (91.8%) arms, but the TI group had a significantly lower mean CD4 count (484 cells/mm³ vs. 655 cells/mm³). The percentage of days using drugs was 37.5% in the TI arm and 99% in the continuous-therapy arm. No AIDS-defining events occurred in either group. Diarrhea and neuropathy were more common with continuous therapy, whereas candidiasis was more common with TI. Resistance mutations were detected in 10 patients with detectable viremia (7 in the TI group).

Comment: These positive findings contrast with the negative results from two other CD4-guided TI trials presented at the 2006 Retrovirus Conference, SMART and ANRS 1269. In those trials, the CD4-count threshold for restarting therapy was 250 cells/mm³ and ritonavir-boosted PI therapy was not as commonly used. Ritonavir-boosted PI therapy has been associated with relatively low levels of resistance, and, because it often causes chronic low-level gastrointestinal symptoms (e.g., diarrhea), it may be well suited to treatment interruption at a high CD4-count threshold (>350 cells/mm³). The Staccato findings support efforts to evaluate TI strategies for ritonavir-boosted therapy in resource-constrained areas where PI-based therapy costs more than NNRTI-based therapy.

— Keith Henry, MD

Published in AIDS Clinical Care August 21, 2006

Citation(s):

Ananworanich J et al. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: Results of the Staccato randomised trial. Lancet 2006 Aug 5; 368:459-65.

• Medline abstract (Free)