Single‐tablet regimen is associated with reduced efavirenz withdrawal in antiretroviral naïve or switching for simplification HIV‐infected patients

Abstract

Purpose of the studyEfavirenz (EFV) is still discussed for its high rate of interruption due to adverse event, in particular central nervous system side effects (CNS-SE). Aim of the study was to define if better drug formulations up to single tablet regimen (STR), including (EFV) plus NRTI backbone (tenofovir-emtricitabine), reduced the risk of interruption.MethodsFrom the database of two reference centers, patients starting any cART regimen including EFV+2 NRTI or switching to EFV+2 NRTI for simplification after virological suppression were selected. Probability of interruption by virological failure, side effects, CNS-SE and any cause were assessed with survival analysis and Cox proportional hazard model.Summary of resultsOverall, 533 patients, starting EFV-containing regimen from May 1998 to March 2012, were included (51.2% naïve, 48.8% switched). Patients characteristics: males 70.7%, median age 39 years, injecting drug use (IDU) 11.2%, median nadir CD4 194/mmc, median CD4 at EFV start 305/mmc: 38.7% started BID regimen, 43.9% OD regimen and 17.4% STR. At survival analysis, the overall proportion of EFV interruption was 19.1% at 1 year and 33.0% at 3 years; interruption for virological failure were 2.8% and 7.4% and for toxicity 10.2% and 15.9%, respectively. CNS-SE accounted for about half of interruptions for toxicity (5.7% and 8.0% at 1 and 3 years, respectively). Naïve patients had a higher risk of interruption as compared to switched patients: 37.7% vs. 28.0% at 3 years (p=0.06). While no significant difference was observed comparing OD vs. B ID regimens, starting with STR was associated with significant lower proportion of overall interruption at 3 years (17.1% vs. 36.6%, p<0.01). No virological failure was observed with STR up to 3 years (0.0% vs. 8.9%, p=0.05); no difference of interruption by overall toxicity and higher, though non-significant, frequency of interruption by CNS-SE (12.8% vs. 6.8%) were also observed. STR also accounted for lower proportion of interruption by patient wish, including low adherence (1.5% vs. 12.3%, p=0.01). At adjusted Cox model, STR (HR: 0.44; 95% CI: 0.26–0.77) and male gender (HR: 0.71; 95% CI: 0.53–0.97) were associated with lower risk of EFV interruption and IDU with higher risk (HR: 1.64; 95% CI: 1.11–2.42).ConclusionsIn our experience, EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite keeping CNS toxicity, thus reducing the risk of treatment interruption.