CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.
BACKGROUND
Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance.


METHODS
430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126.


RESULTS
Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups.


CONCLUSIONS
Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.
Ananworanich
Jintanat
J
HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.
Gayet-Ageron
Angèle
A
Le Braz
Michelle
M
Prasithsirikul
Wisit
W
Chetchotisakd
Ploenchan
P
Kiertiburanakul
Sasisopin
S
Munsakul
Warangkana
W
Raksakulkarn
Phitsanu
P
Tansuphasawasdikul
Somboon
S
Sirivichayakul
Sunee
S
Cavassini
Matthias
M
Karrer
Urs
U
Genné
Daniel
D
Nüesch
Reto
R
Vernazza
Pietro
P
Bernasconi
Enos
E
Leduc
Dominic
D
Satchell
Claudette
C
Yerly
Sabine
S
Perrin
Luc
L
Hill
Andrew
A
Perneger
Thomas
T
Phanuphak
Praphan
P
Furrer
Hansjakob
H
Cooper
David
D
Ruxrungtham
Kiat
K
Hirschel
Bernard
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000191:economics / Q000706:statistics & numerical data*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged