A prospective, randomized trial of structured treatment interruption for patients with chronic HIV type 1 infection.
BACKGROUND
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 highly active antiretroviral therapy containing a protease inhibitor.


METHODS
Patients with a CD4 cell count of > or =350 cells/microL and a plasma viral load of <50 copies/mL were randomized to 3 therapy arms: (1) continuous therapy, (2) CD4 cell count-guided 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 > or =350 cells/microL. Intergroup 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 > or =350 cells/microL 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.


CONCLUSIONS
WOWO therapy maintained a CD4 cell count of > or =350 cells/microL 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 count-guided 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.
Cardiello
Peter G
PG
The HIV Netherlands Australia Thailand Research Collaborative, The Thai Red Cross AIDS Research Center, Bangkok, Thailand. PeterCardiello@post.harvard.edu
Hassink
Elly
E
Ananworanich
Jintanat
J
Srasuebkul
Preeyaporn
P
Samor
Tarika
T
Mahanontharit
Apicha
A
Ruxrungtham
Kiat
K
Hirschel
Bernard
B
Lange
Joep
J
Phanuphak
Praphan
P
Cooper
David A
DA
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D008297:Male; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors