Rilpivirine vs Efavirenz for a Viral Load Under 100,000
Rilpivirine vs Efavirenz for a Viral Load Under 100,000
The pooled analysis of the ECHO/THRIVE trials demonstrated that rilpivirine had comparable efficacy to efavirenz over 96 weeks in antiretroviral treatment-naïve patients with baseline viral load ≤ 100 000 copies/mL. At week 96, 84% of rilpivirine- vs. 80% of efavirenz-treated patients achieved < 50 copies/mL, and the mean changes from baseline in CD4 cell count were 224 and 206 cells/μL, respectively. At week 48, the response rates in this subset of patients were 90% for rilpivirine and 84% for efavirenz. There was only a slight decline in response rates in both treatment groups compared with the week 48 responses, as also seen in previous studies of NNRTIs, because of the definition of the (ITT-based) primary efficacy endpoint. The mean changes from baseline in CD4 cell count were +185 and +161 cells/μL for rilpivirine and efavirenz patients, respectively. The week 96 results, therefore, revealed a continued upward trend in CD4 cell count with both rilpivirine and efavirenz.
In the week 48 primary analysis of the overall patient population from ECHO and THRIVE, there were more rilpivirine patients than efavirenz patients with VFres (9% vs. 5%, respectively). However, in patients with baseline viral load ≤ 100 000 copies/mL, the incidence of VFres was comparable between treatment groups at both week 48 (5% with both rilpivirine and efavirenz) and week 96 (8% and 6% for rilpivirine and efavirenz patients, respectively). Thus, over the course of 96 weeks of treatment, the rate of VFres in patients who had a baseline viral load ≤ 100 000 copies/mL was similar in the rilpivirine and efavirenz groups. Furthermore, in both treatment groups the rates of VFres were lower in the second year of the trials, being approximately half those in the first year. A comparable proportion of patients with VFres in each group developed NNRTI RAMs, while a higher proportion of rilpivirine patients with VFres than efavirenz patients with VFres developed N[t]RTI RAMs (mostly M184I/V associated with emtricitabine/lamivudine resistance).
The incidences of discontinuations attributable to AEs and of serious AEs irrespective of relatedness were similar for rilpivirine and efavirenz in the current analysis. However, as for the overall population, rilpivirine was associated with lower incidences of grade 2–4 treatment-related AEs, grade 2–4 treatment-emergent laboratory abnormalities, treatment-related rash and neurological AEs than efavirenz. As previously reported for the overall population, relatively few AEs occurred after week 48 in either treatment group. Also in line with the findings for the overall population, rilpivirine was associated with smaller mean changes from baseline in total cholesterol, LDL cholesterol and triglyceride levels than efavirenz. However, given that HDL cholesterol levels increased more in the efavirenz group than in the rilpivirine group, there was no difference between treatment groups in the change in the total cholesterol/HDL cholesterol ratio. The increase in serum creatinine seen in the rilpivirine group occurred after 2 weeks and remained stable thereafter. Cystatin C clearance did not decrease in the THRIVE trial, so this increase was probably related to changes in tubular creatinine secretion.
In summary, these results suggest that rilpivirine, either as a single-tablet regimen or as a single agent combined with other antiretrovirals, is a valuable therapeutic option for the treatment of antiretroviral treatment-naïve, HIV-1-infected adults with a viral load ≤ 100 000 copies/mL.
Discussion
The pooled analysis of the ECHO/THRIVE trials demonstrated that rilpivirine had comparable efficacy to efavirenz over 96 weeks in antiretroviral treatment-naïve patients with baseline viral load ≤ 100 000 copies/mL. At week 96, 84% of rilpivirine- vs. 80% of efavirenz-treated patients achieved < 50 copies/mL, and the mean changes from baseline in CD4 cell count were 224 and 206 cells/μL, respectively. At week 48, the response rates in this subset of patients were 90% for rilpivirine and 84% for efavirenz. There was only a slight decline in response rates in both treatment groups compared with the week 48 responses, as also seen in previous studies of NNRTIs, because of the definition of the (ITT-based) primary efficacy endpoint. The mean changes from baseline in CD4 cell count were +185 and +161 cells/μL for rilpivirine and efavirenz patients, respectively. The week 96 results, therefore, revealed a continued upward trend in CD4 cell count with both rilpivirine and efavirenz.
In the week 48 primary analysis of the overall patient population from ECHO and THRIVE, there were more rilpivirine patients than efavirenz patients with VFres (9% vs. 5%, respectively). However, in patients with baseline viral load ≤ 100 000 copies/mL, the incidence of VFres was comparable between treatment groups at both week 48 (5% with both rilpivirine and efavirenz) and week 96 (8% and 6% for rilpivirine and efavirenz patients, respectively). Thus, over the course of 96 weeks of treatment, the rate of VFres in patients who had a baseline viral load ≤ 100 000 copies/mL was similar in the rilpivirine and efavirenz groups. Furthermore, in both treatment groups the rates of VFres were lower in the second year of the trials, being approximately half those in the first year. A comparable proportion of patients with VFres in each group developed NNRTI RAMs, while a higher proportion of rilpivirine patients with VFres than efavirenz patients with VFres developed N[t]RTI RAMs (mostly M184I/V associated with emtricitabine/lamivudine resistance).
The incidences of discontinuations attributable to AEs and of serious AEs irrespective of relatedness were similar for rilpivirine and efavirenz in the current analysis. However, as for the overall population, rilpivirine was associated with lower incidences of grade 2–4 treatment-related AEs, grade 2–4 treatment-emergent laboratory abnormalities, treatment-related rash and neurological AEs than efavirenz. As previously reported for the overall population, relatively few AEs occurred after week 48 in either treatment group. Also in line with the findings for the overall population, rilpivirine was associated with smaller mean changes from baseline in total cholesterol, LDL cholesterol and triglyceride levels than efavirenz. However, given that HDL cholesterol levels increased more in the efavirenz group than in the rilpivirine group, there was no difference between treatment groups in the change in the total cholesterol/HDL cholesterol ratio. The increase in serum creatinine seen in the rilpivirine group occurred after 2 weeks and remained stable thereafter. Cystatin C clearance did not decrease in the THRIVE trial, so this increase was probably related to changes in tubular creatinine secretion.
In summary, these results suggest that rilpivirine, either as a single-tablet regimen or as a single agent combined with other antiretrovirals, is a valuable therapeutic option for the treatment of antiretroviral treatment-naïve, HIV-1-infected adults with a viral load ≤ 100 000 copies/mL.