A5241: The Optimized Treatment that Includes or Omits NRTIs (OPTIONS) Trial: A Randomized Strategy Study for HIV-1-Infected Treatment-Experienced Subjects Using the cPSS to Select an Effective Regimen

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials. Objective: To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents. Design: Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394). Setting: Outpatient HIV clinics. Participants: Treatment-experienced patients with HIV infection and viral resistance. Intervention: Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs. Measurements: The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment. Results: 360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group. Limitation: Unblinded study design, and the study may not be applicable to resource-poor settings. Conclusion: Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population.