Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.
<h4>Background</h4>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.<h4>Methods and findings</h4>We conducted...
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0014764&type=printable |
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| author | Mark Holodniy Sheldon T Brown D William Cameron Tassos C Kyriakides Brian Angus Abdel Babiker Joel Singer Douglas K Owens Aslam Anis Ruth Goodall Fleur Hudson Mirek Piaseczny John Russo Martin Schechter Lawrence Deyton Janet Darbyshire OPTIMA Team |
| author_facet | Mark Holodniy Sheldon T Brown D William Cameron Tassos C Kyriakides Brian Angus Abdel Babiker Joel Singer Douglas K Owens Aslam Anis Ruth Goodall Fleur Hudson Mirek Piaseczny John Russo Martin Schechter Lawrence Deyton Janet Darbyshire OPTIMA Team |
| author_sort | Mark Holodniy |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and findings</h4>We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl 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/µl, 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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00050089. |
| format | Article |
| id | doaj-art-2c4509931d9148c6bef68699da06fc27 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-2c4509931d9148c6bef68699da06fc272025-08-20T02:08:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1476410.1371/journal.pone.0014764Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.Mark HolodniySheldon T BrownD William CameronTassos C KyriakidesBrian AngusAbdel BabikerJoel SingerDouglas K OwensAslam AnisRuth GoodallFleur HudsonMirek PiasecznyJohn RussoMartin SchechterLawrence DeytonJanet DarbyshireOPTIMA Team<h4>Background</h4>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.<h4>Methods and findings</h4>We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl 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/µl, 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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00050089.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0014764&type=printable |
| spellingShingle | Mark Holodniy Sheldon T Brown D William Cameron Tassos C Kyriakides Brian Angus Abdel Babiker Joel Singer Douglas K Owens Aslam Anis Ruth Goodall Fleur Hudson Mirek Piaseczny John Russo Martin Schechter Lawrence Deyton Janet Darbyshire OPTIMA Team Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. PLoS ONE |
| title | Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. |
| title_full | Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. |
| title_fullStr | Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. |
| title_full_unstemmed | Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. |
| title_short | Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. |
| title_sort | results of antiretroviral treatment interruption and intensification in advanced multi drug resistant hiv infection from the optima trial |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0014764&type=printable |
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