1. Response to Antiretroviral Treatment In an Ethiopian Hospital Samuel Hailemariam, MD, MPH; J Allen McCutchan, MD, MSc Meaza Demissie, MD, PMH, PHD; Alemayehu Worku, PHD; ICASA 2011, Addis Ababa 1

2. Background Studies of ART outcomes in multiple RLS have found increased mortality in the first month of therapy. To compare outcomes of ART to those in other RLS and identify determinants of treatment failure in Ethiopian, we reviewed the experience in a large Ethiopian Defence hospital. 2steve@validinternational.org

3. Methods Methods Retrospective chart review of open cohort of patients in an ART clinic in Addis Ababa All 709 adults who had baseline screening and started combination of ART from 2005 to 2009 were studied Outcomes = Survival, immunologic and clinical treatment failure and adverse effects Data analysis –Cox proportional hazard model –Kaplan Meier survival analysis –Log rank test for differences in survival time –General Linear model to examine change overtime 3

4. Baseline Characteristics Sex = 61% men Mean Age = 34 years Mean weight = 52 kg Mean CD4 count = 99 cells /ml Mean FU time were 12.5 months Most common ART regimens: –D4T, 3TC, and NVP (45%) and –AZT, 3TC, NVP (31%) 4steve@validinternational.org

5. Patterns of Response to ART Of the 709 who started ART –47% were still followed on ART –18% died, – 9% were LTFU –11% had major ART side effects –16% changed regimen because of : Side effects/toxicity - 64% New TB - 23% Treatment failure - 6% 5steve@validinternational.org

6. Patterns of Response to ART Overall 24% of patients starting ART failed: –18% died 47% in the 1 st month 64% in the first 3 months –7 % failed immunologically (low or failing CD4 count by WHO criteria) 64% of failures occurred between 6-12 months64% of failures occurred between 6-12 months –10% failed clinically (new OIs): 9 % had new TB 1 % had others OIs 6steve@validinternational.org

7. 7steve@validinternational.org Greater CD4 Count Increases in first 6 months Months after Starting ART 181260 300 250 200 150 100 50 Means of CD4 cell /ml

8. 8steve@validinternational.org 403020100. 1.0 0.8 0.6 0.4 0.2 0.0 Mortality Treatment Failure & Mortality

9. Univariate Predictors of Failure (Cox Model) Hazard Ratio –Male sex 1.4 –Age > 50 2.0 –Baseline CD4 count < 100 2.0 –Baseline haemoglobin < 10mg/dl 2.3 –Side effects of ART 2.0 –Functional status bedridden 3.8 –WHO stage 4 and 3 4.1/ 2.2 –Prior exposure to ARV 2.8 –TB treatment at the start of ART 2.8 –Poor or fair adherence 5.1

10. Multivariate Predictors of ART failure Hazard ratio –Poor adherence 5.8 –Prior exposure to ARV 4.2 –Side effects of ART 2.2 –Low functional status (bedridden) 2.0 –Low haemoglobin level (<10mg/dl) 1.7 –Male sex 1.7

11. Time to any outcome failure (in months) 40 30 20 10 0 1.0 0.8 0.6 0.4 0.2 0.0 Good adherence Poor/fair adherence 11steve@validinternational.org Poor Adherence is Associated with Failure (P< 0.001)

12. ART Side Effects Predict Survival (P <0.001)

13. Conclusions and Recommendations Responses to ART in an Ethiopian hospital ART clinics were similar to those in other RLS Early mortality is much higher in RLS than in developed countries To reduce this excess early mortality –Diagnose and treat HIV at higher CD4 counts –Improve quality of management of OIs –Focus monitoring on patients at high risk for death To reduce later treatment failure –Detect virologic ART failure by measuring viral loads –Improve adherence monitoring and counselling

14. Improve diagnosis and treatment of potential causes of early deaths including: –Undiagnosed OIs or IRIS (Immune Reconstitution Inflammatory Syndrome) –Delayed initiation of ART –Primary ART resistance –Drug interactions –Side effects/ART toxicity –Poor adherence 14steve@validinternational.org Recommendations for Further Research

15. Thank you! 15steve@validinternational.org