Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial

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, Sandro Cinti, David Rimland, Anthony Amoroso, Kris Ann Oursler, David Johnson, Tiffany Surles, David Thornton, Judith Strymish, Catherine Fleming, Juan Bandres, Catherine Martyn, Alan George Smulian, Robert Bonomo, Gopal Yadavalli, Janet M Briggs, Stephan Hawes, Roger Bedimo, David Margolis, Kenneth Wilson, Bradley S Bender, Constance Pachucki, Maria Rodriguez-Barradas, Matthew B Goetz, Rodney Wishnow, Stephan Berman, Nancy Klimas, Gordon Dickinson, Mark Holodniy, Victoria Faria, Joel Maslow, Chris Reust, Thomas T Ward, Melissa Murphy, Gregory Anstead, Raymond Chung, David Looney, Sonia Saavedra, Carlos R Rivera-Vazquez, Cynthia Gibert, Michael Kozal, Michael O Rigsby, Brian Gazzard, Chris Higgins, Charlotte Mahuma, Margaret Johnson, Mike Youle, Zoe Cuthbertson, Alan Winston, John Walsh, Norman Gariwa, Ranjababu Kulasegaram, Isabelle Jendrulek, Brian Angus, Jean Tobin, Linda Tucker, David Dockrell, Chris Care, Ian Williams, David Cornforth, Chloe Orkin, James Hand, Alain Piché, Sylvie Trottier, Robert O'Brien, Alain Martel, D William Cameron, Bill Thompson, Edward Ralph, Sharon Walmsley, Peter Ford, Wendy Wobeser, Don Kilby, Walter Schlech, Brian Conway, John Gill, Stephen Shafran, 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, Sandro Cinti, David Rimland, Anthony Amoroso, Kris Ann Oursler, David Johnson, Tiffany Surles, David Thornton, Judith Strymish, Catherine Fleming, Juan Bandres, Catherine Martyn, Alan George Smulian, Robert Bonomo, Gopal Yadavalli, Janet M Briggs, Stephan Hawes, Roger Bedimo, David Margolis, Kenneth Wilson, Bradley S Bender, Constance Pachucki, Maria Rodriguez-Barradas, Matthew B Goetz, Rodney Wishnow, Stephan Berman, Nancy Klimas, Gordon Dickinson, Mark Holodniy, Victoria Faria, Joel Maslow, Chris Reust, Thomas T Ward, Melissa Murphy, Gregory Anstead, Raymond Chung, David Looney, Sonia Saavedra, Carlos R Rivera-Vazquez, Cynthia Gibert, Michael Kozal, Michael O Rigsby, Brian Gazzard, Chris Higgins, Charlotte Mahuma, Margaret Johnson, Mike Youle, Zoe Cuthbertson, Alan Winston, John Walsh, Norman Gariwa, Ranjababu Kulasegaram, Isabelle Jendrulek, Brian Angus, Jean Tobin, Linda Tucker, David Dockrell, Chris Care, Ian Williams, David Cornforth, Chloe Orkin, James Hand, Alain Piché, Sylvie Trottier, Robert O'Brien, Alain Martel, D William Cameron, Bill Thompson, Edward Ralph, Sharon Walmsley, Peter Ford, Wendy Wobeser, Don Kilby, Walter Schlech, Brian Conway, John Gill, Stephen Shafran

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 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.

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.

Trial registration: Clinicaltrials.gov NCT00050089.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Trial profile and patient flow.
Figure 1. Trial profile and patient flow.
Figure 2. Time to first AIDS event…
Figure 2. Time to first AIDS event or death by treatment strategy.
A) Intensification versus standard antiretroviral therapy (ART); B) ART interruption versus continuation. Time to first non HIV-related serious adverse event (SAE) by C) intensification versus standard ART; D) ART interruption versus continuation.
Figure 3. Immunological and virological changes over…
Figure 3. Immunological and virological changes over time by treatment strategy.
A) CD4 count change, intensification vs. standard antiretroviral therapy (ART); B) CD4 count change, ART interruption vs. continuation; C) HIV-1 viral load change, intensification vs. standard ART; D) HIV-1 viral load change, ART interruption vs. continuous.

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Source: PubMed

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