Background: Factors associated with virologic failure as well as with transient HIV-1 RNA elevations (blips) in patients receiving NNRTI-containing regimens have not been clearly defined.

Methods: Data from 158 patients treated with EFV-containing regimen between 1999 and 2001 were analyzed, 76 (47.8%) HAART-naïve and 83 (52.2%) simplified therapy from a PI-containing regimen switching with undetectable HIV-RNA. Virological rebound was considered as 2 consecutive HIV-RNA elevations and time of rebound was taken at the first one. Treatment failure was defined as both occurrence of virological rebound and interruption by any cause. Blips were considered as single HIV-RNA elevations >80 copies/mL between 2 undetectable HIV-RNA.

Results: At survival analysis, overall rate of virological rebound at 72 weeks was 22.7% and rate of treatment failure was 36.7%. Blips were observed in 47 (29.7%) of 134 suppressed patients. Rates did not significantly differ between naïve and switched patients. 28 patients (17.7%) reported central nervous system side effects (CNS-SE), such as hallucinations, dizziness, lack of concentration, insomnia and abnormal dreams. The rate of patients reporting CNS-SE was 31.0% in the first 3 months (41.2% in the first month) and decreased over time (5.9% after 12 months). 11 patients interrupted the therapy due to CNS-SE (40.7% of all interruptions by side effects). At a multiple logistic regression model, occurrence of blips was associated to CNS-SE (OR: 7.0; 95% CI: 1.2-43.9) and older age (1.2; 1.1-1.4, for each year). By Cox model, CNS-SE (HR: 5.1; 95% C.I.:1.2-22.0) and male gender (4.1; 1.2-14.0) were found associated to VR and CNS-SE (4.2; 1.7-10.3), male gender (2.2; 1.0-4.5), and anti-HCV positivity (2.4, 1.2-5.0) were all correlated to treatment failure. Type of patients (naïve or switched), sex, age, CD4+ count, category of exposure, AIDS diagnosis, active drug using, blips, and occurrence of other SE did not correlate with virological rebound or treatment failure.

Conclusions: CNS-SE emerged as a major factor of treatment failure in HIV patients treated with EFV-containing regimen. Association with blips, suggesting spontaneous break of treatment by patients, could enhance development of resistance, considering low genetic barrier of the drug. Declining incidence of CNS-SE over time could be relevant for control of this side effect.