eprintid: 1395866
rev_number: 45
eprint_status: archive
userid: 608
dir: disk0/01/39/58/66
datestamp: 2013-06-10 18:55:32
lastmod: 2021-12-13 01:59:14
status_changed: 2013-06-10 18:55:32
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Holodniy, M
creators_name: Brown, ST
creators_name: Cameron, DW
creators_name: Kyriakides, TC
creators_name: Angus, B
creators_name: Babiker, A
creators_name: Singer, J
creators_name: Owens, DK
creators_name: Anis, A
creators_name: Goodall, R
creators_name: Hudson, F
creators_name: Piaseczny, M
creators_name: Russo, J
creators_name: Schechter, M
creators_name: Deyton, L
creators_name: Darbyshire, J
creators_name: OPTIMA Team, 
title: Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial
ispublished: pub
divisions: UCL
divisions: B02
divisions: D65
divisions: J38
keywords: Structured treatment interruption, quality-of-life, cross-resistance, clinical progression, virological failure, mega-haart, cohort, therapy, inhibitors, virus
note: 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.
abstract: 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.
date: 2011-03-31
publisher: PUBLIC LIBRARY SCIENCE
official_url: http://dx.doi.org/10.1371/journal.pone.0014764
vfaculties: VFPHS
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_source: Web of Science
elements_id: 305862
doi: 10.1371/journal.pone.0014764
language_elements: EN
lyricists_name: Babiker, Abdel
lyricists_name: Goodall, Ruth
lyricists_name: Hudson, Fleur
lyricists_id: ABABI41
lyricists_id: RLGOO00
lyricists_id: FHUDS08
full_text_status: public
publication: PLOS ONE
volume: 6
number: 3
article_number: e14764
pagerange: -
issn: 1932-6203
citation:        Holodniy, M;    Brown, ST;    Cameron, DW;    Kyriakides, TC;    Angus, B;    Babiker, A;    Singer, J;                                         ... OPTIMA Team; + view all <#>        Holodniy, M;  Brown, ST;  Cameron, DW;  Kyriakides, TC;  Angus, B;  Babiker, A;  Singer, J;  Owens, DK;  Anis, A;  Goodall, R;  Hudson, F;  Piaseczny, M;  Russo, J;  Schechter, M;  Deyton, L;  Darbyshire, J;  OPTIMA Team;   - view fewer <#>    (2011)    Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial.                   PLOS ONE , 6  (3)    , Article e14764.  10.1371/journal.pone.0014764 <https://doi.org/10.1371/journal.pone.0014764>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1395866/1/journal.pone.0014764.pdf