Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

Abstract

BackgroundGuidance 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 FindingsWe 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 log10 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.ConclusionsWe 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 RegistrationClinicaltrials.gov NCT00050089

Predictive value of HIV‐1 replication capacity and phenotypic susceptibility scores in antiretroviral treatment‐experienced patients

“…Participants could change ARVs during the trial as long as they maintained their allocated treatment strategy. No significant differences were found in the primary outcome measure by treatment arm [25].…”

“…Participants could change ARVs during the trial as long as they maintained their allocated treatment strategy. No significant differences were found in the primary outcome measure by treatment arm [25].For the purpose of this substudy, we combined the subgroups receiving standard and mega-ARV regimens within the ARDFP and the no-ARDFP groups. Viral RC and phenotypic drug susceptibility were retrospectively tested on frozen, stored (-70 o C) ethylenediaminetetraacetic acid (EDTA) plasma samples collected from OPTIMA participants enrolled at Veterans Administration (VA) hospitals.…”

Cost-Effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients With Multidrug-Resistant HIV Disease

“…We assumed that discontinuation of older drugs was not associated with worse virologic outcomes, since randomized trials have demonstrated no benefit from continuing multiple conventional antiretroviral drugs. 4, 27 We assumed that new regimens might contain some older drugs for two reasons. First, they might have residual antiretroviral activity.…”

“…4 We estimated parameters that were not available within OPTIMA from the literature (Supplementary Digital Content 1).…”

“…3 In a recent trial of treatment options for patients with advanced multi-drug resistant HIV, 35% of patients died over 4 years and 27% experienced at least one AIDS-defining event. 4, 5 …”