1. Efavirenz Use Not Associated With Depressive Episodes, According to Analysis of Randomized Clinical Trial Outcomes Slideset on: Journot V, Chene G, De Castro N, et al. Use of efavirenz is not associated with a higher risk of depressive disorders: a substudy of the randomized clinical trial ALIZE-ANRS 099. Clin Infect Dis. 2006;42:1790-1799.

2. clinicaloptions.com/hiv Efavirenz Use Not Associated With Depressive Episodes Journot V, et al. Clin Infect Dis. 2006;42:1790-1799. Background and Rationale  Efavirenz frequently causes early, transient CNS adverse reactions  Some reports have associated efavirenz with acute depression and suicidal ideation, especially among patients with history of depression –Other studies found no association  Current study examined efavirenz association with depressive disorders by comparing incidence of disorders between patients switching to efavirenz-based regimen and patients continuing on PI-based regimen

3. clinicaloptions.com/hiv Efavirenz Use Not Associated With Depressive Episodes Journot V, et al. Clin Infect Dis. 2006;42:1790-1799. Summary of Study Design  Data from patients participating in ALIZE-ANRS 099 –Patients with controlled HIV-1 infection received stable PI- based regimen or switched to once-daily efavirenz, didanosine, and emtricitabine  Depressive symptoms assessed throughout study –Self-administered Centre for Epidemiologic Studies- Depression Scale questionnaire at Weeks 0, 24, 48 –Patients asked every 8 weeks the frequency of depressive mood and suicidal ideation since prior visit –Medical charts reviewed for use of antidepressants at baseline, during study, and during follow-up

4. clinicaloptions.com/hiv Efavirenz Use Not Associated With Depressive Episodes Journot V, et al. Clin Infect Dis. 2006;42:1790-1799. Baseline Characteristics Characteristic Efavirenz-Based Treatment (n = 178) PI-Based Treatment (n = 177) Median age, yrs (IQR)41 (36-47)41 (35-51) Male, n (%)152 (85)154 (87) AIDS, n (%)50 (28)45 (25) Median CD4+ cell count, cells/mm 3 (IQR)509 (375-756)547 (396-740) History of depressive disorder, n (%)15 (8)16 (9)  Depression, n1513  Suicidal ideation, n10  Suicide attempt, n03 Receipt of antidepressants at baseline, n (%)8 (4)8 (5)

5. clinicaloptions.com/hiv Efavirenz Use Not Associated With Depressive Episodes Journot V, et al. Clin Infect Dis. 2006;42:1790-1799. Main Findings  No discontinuations caused by depressive episodes  Incidence of depressive episodes, new antidepressant use during study, follow-up comparable between arms  Independent predictors of depressive episode during treatment: –Age, per 10-year decrease (HR, 1.61; 95% CI, 1.04-2.50; P =.03) –History of depressive disorders (HR, 4.97; 95% CI, 2.05- 12.02; P =.0004)

6. clinicaloptions.com/hiv Efavirenz Use Not Associated With Depressive Episodes Journot V, et al. Clin Infect Dis. 2006;42:1790-1799. Incidence of Depressive Episodes Outcome Efavirenz-Based Treatment (n = 178) PI-Based Treatment (n = 177) Patients experiencing ≥ 1 depressive episode, n (%)15 (8)12 (7) Depressive episode, no. of events1612  Depression1511  Suicide attempt13 Depressive episode event severity, no. of events  Mild33  Moderate116  Severe14  Life threatening11 New use of antidepressants during treatment or follow-up, n (%) 12 (7) (n = 170) 7 (4) (n = 169) Depressive episode incidence/100 patient-years (95% CI) 11 (5-16)9 (4-13)

7. clinicaloptions.com/hiv Efavirenz Use Not Associated With Depressive Episodes Journot V, et al. Clin Infect Dis. 2006;42:1790-1799. Key Conclusions  No difference in incidence of depressive episodes between NNRTI-naive patients switching to efavirenz- based regimen and those remaining on PI-based regimen  High incidence of depressive episodes among total study population (10 cases/100 person-years) –Concentrated among patients with history of depressive disorders at baseline  Age and history of depressive disorders significantly predicted depressive episode during treatment