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Baseline antiretroviral resistance profile and correlation with clinical events in the OPTIMA trial
Presented by Mark Holodniy, United States.
Holodniy M.1, Singer J.2, Ayers D.2, Harrigan R.2, Brown S.3, Cameron W.4, Kyriakides T.5, Angus B.6, OPTIMA Study Team
1Department of Veterans Affairs, Office of Public Health Surveillance and Research, Palo Alto, United States, 2Canadian HIV Trials Network, Vancouver, Canada, 3Bronx VA Medical Center, New York, United States, 4University of Ottawa Hospital, Ottawa, Canada, 5West Haven VA CSPCC, West Haven, United States, 6UK MRC, London, United Kingdom
Objectives: To determine whether baseline antiretroviral (ARV) resistance characteristics are correlated with virologic and clinical outcome in the OPTIMA trial.
Methods: Patients on ARV therapy with multi-drug resistance (MDR) were randomized to a 3-month ARV drug-free period (ARDFP) vs. no ARDFP followed by a new standard ARV (< 4 ARVs) or MegaART (>5 ARVs) regimen versus no ARDFP (immediate change to new ARV regimen of standard vs. MegaART). The primary endpoint is new AIDS illness or death. Treatment assignment is still blinded. Baseline resistance was assessed by genotype and virtual phenotype (vP). Cox proportional step-wise hazards models were derived to determine whether baseline variables: CD4 count, pVL, number and class of prior ARVs used, ARV class mutation score (MS), and genotypic and phenotypic susceptibility scores (GSS and PSS) were associated with virologic success (> 1 log/mL drop at 24 weeks) and primary endpoints.
Results: 368 patients (98% male, mean age 48) were enrolled. Mean baseline HIV RNA = 4.67 log10/mL and CD4 = 127 cells/mm3. Prior ARV utilization (mean = 10 ARVs) included: 3.3 PIs, 1.4 NNRTIs and 5.2 NRTIs. All ARV mean fold-changes were above the vP clinical cutoff. Primary mutations found in > 49% of patients included K103N, M184V, T215Y, and L90M. Of the variables considered, only baseline CD4 count was significantly correlated with death or development of new AIDS illnesses. Lower CD4 count and PSS, and higher PI MS correlated with smaller likelihood of virologic success.
Conclusions: In this clinically advanced population, the prevalence of ARV resistance is significant and treatment options are limited. ARV resistance was highly correlated with prior ARV exposure. Although some ARV resistance markers were correlated with virologic response, none were predictive of future clinical events or death. Only baseline CD4 count correlated with clinical events.
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