A Prospective, Randomized Trial of Structured Treatment Interruption for Patients with Chronic HIV

Structured treatment interruption was evaluated in 74 patients who had been pretreated with antiretrovirals, consisting of 2 nucleoside reverse-transcriptase inhibitors (NRTIs) for 1 year followed by 3 years of HAART.

Patients with a CD4 cell count of 350 cells/L and a plasma viral load of <50 copies/mL were randomized to 3 therapy arms: (1) continuous therapy, (2) CD4 cell countguided theory, and (3) week-on/week-off (WOWO) therapy.

The efficacy and safety of structured treatment interruption and antiretroviral use were evaluated in human immunodeficiency type 1 (HIV-1)-infected patients. The study end points were percentage of patients who developed AIDS or who died and a CD4 cell count of 350 cells/L. Inter-group differences were analyzed using analysis of variance and Kruskal-Wallis tests.

Results   

Baseline characteristics at the start of the structured treatment interruption were similar. At week 48, no patient had died, and 1 patient in the WOWO group had an AIDS-defining condition.

The proportions of patients with a CD4 cell count of 350 cells/L were 100%, 87%, and 96% in treatment arms 1, 2, and 3, respectively. The percentages of weeks of antiretroviral use were 100%, 41.1%, and 69.8% in arms 1, 2, and 3, respectively.

The adverse events were not significantly different among arms (P = .27). Thirty-one percent of patients in the WOWO group experienced virological failure.

Conclusion

WOWO therapy maintained a CD4 cell count of 350 cells/L in almost all patients but was associated with high virological failures rates (possibly resulting from previous dual-NRTI therapy), indicating that this strategy is less useful. Receipt of CD4 cell countguided therapy resulted in comparable clinical outcomes to continuous therapy and may save antiretroviral-associated costs, but this needs to be confirmed by a larger trial.

(See the editorial commentary by Montaner and others)

The HIV Netherlands Australia Thailand Research Collaborative, The Thai Red Cross AIDS Research Center, and Faculty of Medicine, Division of Infectious Diseases, Chulalongkorn University, Bangkok, Thailand; International Antiviral Therapy Evaluation Center, Academic Medical Center, University of Amsterdam, The Netherlands; University Hospital of Geneva, Switzerland; and National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.

02/02/05

Reference
P G Cardiello and others. A Prospective, Randomized Trial of Structured Treatment Interruption for Patients with Chronic HIV Type 1 Infection. Clinical Infectious Diseases 40(4): 594-600. February 15, 2005.