Rilpivirine vs Efavirenz for a Viral Load Under 100,000
Rilpivirine vs Efavirenz for a Viral Load Under 100,000
Objectives These 96-week, ECHO/THRIVE pooled analyses evaluated data for antiretroviral treatment-naïve, HIV-1-infected adults with viral load (VL) ≤ 100 000 HIV-1 RNA copies/mL receiving rilpivirine or efavirenz.
Methods ECHO and THRIVE were phase 3, randomized, double-blind trials. Patients received rilpivirine 25 mg once daily (qd) or efavirenz 600 mg qd, with a fixed (ECHO) or investigator-chosen (THRIVE) nucleoside/tide reverse transcriptase inhibitor (N[t]RTI) background regimen. Response rate (the percentage of patients with VL < 50 copies/mL, using an intent-to-treat-population, time-to-loss-of-virological-response algorithm), virological failure (VF), resistance development, safety and tolerability were evaluated.
Results Baseline characteristics were comparable between the rilpivirine (n = 368) and efavirenz (n = 329) groups. At week 96, response rates [84% for rilpivirine vs. 80% for efavirenz; difference 4.0%; 95% confidence interval (CI) –1.7% to 9.7%] and incidences of VF for the resistance analysis (VFres) (8% for rilpivirine vs. 6% for efavirenz; P = 0.46) were similar in the two groups. Among patients with VFres, a comparable proportion in each group developed nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). Among those with VFres, more patients in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs, mostly M184I/V. The mean (95% CI) CD4 cell count increased from baseline to week 96 by 224 (208–240) cells/μL in the rilpivirine group and by 206 (188–225) cells/μL in the efavirenz group. Treatment-related grade 2–4 overall adverse events, any rash and dizziness were less frequent for rilpivirine than for efavirenz (P < 0.0001).
Conclusions Rilpivirine demonstrated antiviral efficacy similar to that of efavirenz in antiretroviral treatment-naïve adults with baseline VL ≤ 100 000 copies/mL over 96 weeks. Frequencies of VFres and emergent NNRTI RAMs in each group were similar. More patients with VFres in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs (mostly M184I/V). Rilpivirine had a more favourable safety/tolerability profile than efavirenz.
The nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (TMC278), combined with other antiretroviral drugs, is approved for use in antiretroviral treatment-naïve, HIV-1-infected adults in several countries including the USA, Canada and Europe. In many countries, the indication for rilpivirine is restricted to patients with a viral load ≤ 100 000 HIV-1 RNA copies/mL. These approvals were based on the 48-week results of the phase 3 ECHO (Efficacy Comparison in treatment-naïve HIV-infected subjects Of TMC278 and efavirenz) and THRIVE (TMC278 against HIV, in a once-daily RegImen Versus Efavirenz) trials. A single tablet, once-daily regimen containing rilpivirine, emtricitabine and tenofovir disoproxil fumarate has been approved in the USA, Canada, Europe and elsewhere.
Rilpivirine demonstrated noninferior antiviral efficacy vs. efavirenz in the primary preplanned week 48 pooled analyses of the ECHO/THRIVE trials. Rilpivirine had an improved tolerability profile compared with efavirenz, with fewer discontinuations because of adverse events (AEs). Rilpivirine was associated with a higher virological failure rate than efavirenz. Baseline viral load had a greater effect on the virological failure rate for rilpivirine than for efavirenz. Therefore, efficacy, virology and safety were assessed in the predefined subset of ECHO/THRIVE patients with a baseline viral load ≤ 100 000 copies/mL.
Patients receiving rilpivirine who had a baseline viral load ≤ 100 000 copies/mL demonstrated a higher response rate at week 48 than those receiving efavirenz; 90% of rilpivirine patients vs. 84% of efavirenz patients achieved a viral load < 50 copies/mL [using an intent-to-treat, time-to-loss-of-virological-response (ITT-TLOVR) algorithm]. In this subpopulation, the rate of virological failure was the same for rilpivirine and efavirenz. Here we report the efficacy, virology and safety results in patients with baseline viral load ≤ 100 000 copies/mL, after 96 weeks of treatment.
*Data contained in this article were presented at the 11th International Congress on Drug Therapy in HIV Infection, 11–15 November 2012, Glasgow, UK (Abstract P270).
Abstract and Introduction
Abstract
Objectives These 96-week, ECHO/THRIVE pooled analyses evaluated data for antiretroviral treatment-naïve, HIV-1-infected adults with viral load (VL) ≤ 100 000 HIV-1 RNA copies/mL receiving rilpivirine or efavirenz.
Methods ECHO and THRIVE were phase 3, randomized, double-blind trials. Patients received rilpivirine 25 mg once daily (qd) or efavirenz 600 mg qd, with a fixed (ECHO) or investigator-chosen (THRIVE) nucleoside/tide reverse transcriptase inhibitor (N[t]RTI) background regimen. Response rate (the percentage of patients with VL < 50 copies/mL, using an intent-to-treat-population, time-to-loss-of-virological-response algorithm), virological failure (VF), resistance development, safety and tolerability were evaluated.
Results Baseline characteristics were comparable between the rilpivirine (n = 368) and efavirenz (n = 329) groups. At week 96, response rates [84% for rilpivirine vs. 80% for efavirenz; difference 4.0%; 95% confidence interval (CI) –1.7% to 9.7%] and incidences of VF for the resistance analysis (VFres) (8% for rilpivirine vs. 6% for efavirenz; P = 0.46) were similar in the two groups. Among patients with VFres, a comparable proportion in each group developed nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). Among those with VFres, more patients in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs, mostly M184I/V. The mean (95% CI) CD4 cell count increased from baseline to week 96 by 224 (208–240) cells/μL in the rilpivirine group and by 206 (188–225) cells/μL in the efavirenz group. Treatment-related grade 2–4 overall adverse events, any rash and dizziness were less frequent for rilpivirine than for efavirenz (P < 0.0001).
Conclusions Rilpivirine demonstrated antiviral efficacy similar to that of efavirenz in antiretroviral treatment-naïve adults with baseline VL ≤ 100 000 copies/mL over 96 weeks. Frequencies of VFres and emergent NNRTI RAMs in each group were similar. More patients with VFres in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs (mostly M184I/V). Rilpivirine had a more favourable safety/tolerability profile than efavirenz.
Introduction
The nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (TMC278), combined with other antiretroviral drugs, is approved for use in antiretroviral treatment-naïve, HIV-1-infected adults in several countries including the USA, Canada and Europe. In many countries, the indication for rilpivirine is restricted to patients with a viral load ≤ 100 000 HIV-1 RNA copies/mL. These approvals were based on the 48-week results of the phase 3 ECHO (Efficacy Comparison in treatment-naïve HIV-infected subjects Of TMC278 and efavirenz) and THRIVE (TMC278 against HIV, in a once-daily RegImen Versus Efavirenz) trials. A single tablet, once-daily regimen containing rilpivirine, emtricitabine and tenofovir disoproxil fumarate has been approved in the USA, Canada, Europe and elsewhere.
Rilpivirine demonstrated noninferior antiviral efficacy vs. efavirenz in the primary preplanned week 48 pooled analyses of the ECHO/THRIVE trials. Rilpivirine had an improved tolerability profile compared with efavirenz, with fewer discontinuations because of adverse events (AEs). Rilpivirine was associated with a higher virological failure rate than efavirenz. Baseline viral load had a greater effect on the virological failure rate for rilpivirine than for efavirenz. Therefore, efficacy, virology and safety were assessed in the predefined subset of ECHO/THRIVE patients with a baseline viral load ≤ 100 000 copies/mL.
Patients receiving rilpivirine who had a baseline viral load ≤ 100 000 copies/mL demonstrated a higher response rate at week 48 than those receiving efavirenz; 90% of rilpivirine patients vs. 84% of efavirenz patients achieved a viral load < 50 copies/mL [using an intent-to-treat, time-to-loss-of-virological-response (ITT-TLOVR) algorithm]. In this subpopulation, the rate of virological failure was the same for rilpivirine and efavirenz. Here we report the efficacy, virology and safety results in patients with baseline viral load ≤ 100 000 copies/mL, after 96 weeks of treatment.
*Data contained in this article were presented at the 11th International Congress on Drug Therapy in HIV Infection, 11–15 November 2012, Glasgow, UK (Abstract P270).