Antiretroviral Therapy at GHESKIO

1. Antiretroviral Therapy at GHESKIO Patrice Sevère, Paul Denis Léger, Estere Michel, Sabine Prince, Jean W. Pape Centres GHESKIO, Port-au-Prince, Haïti Weill Medical College of Cornell University, NewYork, NY, USA Sponsored by: GLOBAL FUNDS

2. Introduction • Data is provided on first 96 adults treated with ART at GHESKIO • We initiated therapy between1999-2002 • We have shown that ART dramatically improved survival. • With the support of the Global Fund for AIDS, TB,and Malaria; we started to increase the number of patients on ART in February 2003

3. ENROLLMENT PROCEDURE Medical visit • Screening for opportunistic infections • Prophylaxis and treatment of OI • Initial lab exams • Verify clinical and lab criteria for ART IEC: Three sessions • Information on ART • GHESKIO and patient responsibilities • Behavioral and Family Planning • Adherence and Retention

4. When to Start? • Endorsed WHO Guidelines; Treat if: • WHO stage IV (clinical AIDS), regardless of CD4 cell count • CD4 cell count available, WHO stages I, II, III with CD4 cell count <200 (or <15%) • CD4 cell count not available, WHO stages II and III (symptomatic HIV disease) with TLC (total lymphocyte count) <1200 • Addition to WHO Guidelines: • HIV symptoms defined locally • Also treat: WHO stages II and III (symptomatic HIV disease) with CD4 200-350 • All patients should be evaluated for TB prior to starting ART; if active TB infection is present, it should be treated first.

5. What treatment regimen to start? • Endorsed WHO Guidelines • Based on convenience, tolerability, cost, and second-line treatment options, first-line therapy should be: • D4T + 3TC + NVP or EFV • AZT + 3TC + NVP or EFV • This regimen should be modified, depending on concomitant conditions: • TB or hepatoxicity: substitute EFV for NVP • Pregnancy or D4T-related peripheral neuropathy: substitute D4T for AZT

6. Improving adherence and retention • FACILITATE COMMUNICATION WITH THE PATIENT • VISIT MONITORING • INCENTIVES • CONTINGENCY PLAN • EDUCATIONAL BROCHURE

7. Educational Brochure • Written in native Creole. • Covers all aspects of ART • Illustrated for illiterate patients

10. Preliminary Results of ART at GHESKIOFebruary-October 2003 • N= 800 (100 Patients per month) • Active : 721 (90%) • Lost to follow-up : 33 (4%) • Deceased : 46 (6%) • Long term N=751 • Short term (PEP) N=49 • Regimens used : AZT/3TC/EFV : 447 (60%) AZT/3TC/NVP : 241 (32%) OTHERS : 63 ( 8.3%)

11. Characteristics Of ART PatientsFebruary – October 2003 N = 800

12. How to monitor therapy? • Clinical evaluations at 1or 2 weeks, 1month, then every 3 months. • Monthly evaluations (e.g., by nurse, pharmacist, social worker, PLWA’s, field workers). • Lab monitoring: at start of therapy and every 6 months thereafter.

13. Table of events *IEC1:General information about ARV, patient/GHESKIO responsibility, guardian/contact identification , contact update **IEC2:Signature of at home visit authorization form, evaluation of HIV reinfection risk level, risk reduction planning FP method proposal - ARV counceling

14. How to assess treatment failure • Adherence should be assessed carefully first. • Clinical definition of treatment failure: Chronic signs/symptoms of HIV disease (e.g., candidal or refractory/recurrent bacterial infections, including salmonellosis; chronic enteropathy; anemia; neutropenia) that either fail to resolve, or resolve and then recur.

15. How to assess treatment failure, cont. • At a minimum, clinical criteria should be used to assess treatment failure. CD4 (and HIV RNA) should be used, if available. • If CD4 cell count available, check every 3 to 6 months. • Failure: >30% decrease from baseline CD4 cell count (or >3% decrease of CD4 percent).

16. What treatment to change to? • If changing for toxicity, can substitute a single drug: • D4T ↔ AZT • NVP ↔ EFV • If changing for treatment failure, depends on prior regimen: • D4T + 3TC + NVP (or EFV) → ZDV + DDI + PI • ZDV + 3TC + NVP (or EFV) → D4T + DDI + PI • PI choices: • IDV (q8h, fasting/water requirements, difficulty with DDI coadministration) • LPV/RTV (necessary to keep cool) • NFV (diarrhea, ?less effective)

17. What about drug resistance? • If possible, samples should be collected at baseline (prior to starting therapy) to assess (later) drug resistance in the community. (AACTG 5175) • If possible, samples should be collected at each visit and particularly at the time of treatment failure to assess (later) drug resistance in the patient.

18. Antiretroviral Adverse ReactionsN:17 • Anemia 10 (<7,5 g/dl) • Severe Rash 5 • Steven Johnson 3 • *CNS (dizziness, bad dreams) seen in 65% of patients on EFV with spontaneous improvement in nearly all.

19. Risk factor for deathN=46 • Wasting syndrome : 46% • Tuberculosis : 25% • Wasting synd/TB : 4% • Poor adherence : 11% • Others : 14% Death occurs early after ART initiation (average 23 days)for a majority of patients : 85%

20. Summary • Excellent response to ARV • Rapid enrollment of patients • Patient retention is good • Future efforts will extend the benefit of ART to larger population of patients