A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda.
BACKGROUND
Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.


METHODS
A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count > or =125 cells/mm(3) and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.


RESULTS
Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).


CONCLUSIONS
Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.


BACKGROUND
ClinicalTrials.gov NCT00339456.
Reynolds
Steven J
SJ
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. sjr@jhmi.edu
Kityo
Cissy
C
Hallahan
Claire W
CW
Kabuye
Geoffrey
G
Atwiine
Diana
D
Mbamanya
Frank
F
Ssali
Francis
F
Dewar
Robin
R
Daucher
Marybeth
M
Davey
Richard T
RT
Mugyenyi
Peter
P
Fauci
Anthony S
AS
Quinn
Thomas C
TC
Dybul
Mark R
MR
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections; D012367:RNA, Viral / Q000097:blood; D017211:Treatment Failure; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load / Q000187:drug effects / Q000379:methods
D044966:Anti-Retroviral Agents; D012367:RNA, Viral