TY  - JOUR
N1  - This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
IS  - 3
AV  - public
Y1  - 2011/03/31/
VL  - 6
TI  - Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial
KW  - Structured treatment interruption
KW  -  quality-of-life
KW  -  cross-resistance
KW  -  clinical progression
KW  -  virological failure
KW  -  mega-haart
KW  -  cohort
KW  -  therapy
KW  -  inhibitors
KW  -  virus
A1  - Holodniy, M
A1  - Brown, ST
A1  - Cameron, DW
A1  - Kyriakides, TC
A1  - Angus, B
A1  - Babiker, A
A1  - Singer, J
A1  - Owens, DK
A1  - Anis, A
A1  - Goodall, R
A1  - Hudson, F
A1  - Piaseczny, M
A1  - Russo, J
A1  - Schechter, M
A1  - Deyton, L
A1  - Darbyshire, J
A1  - OPTIMA Team
JF  - PLOS ONE
SN  - 1932-6203
PB  - PUBLIC LIBRARY SCIENCE
UR  - http://dx.doi.org/10.1371/journal.pone.0014764
ID  - discovery1395866
N2  - Background: Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.Methods and Findings: We conducted a 262 factorial randomized open label controlled trial in patients with a CD4 count <= 300 cells/mu l who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (<= 4 ARVs) or intensive (>= 5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/mu l, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.Conclusions: We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.
ER  -