1. Pre-departure HIV Orientation Session A: Pre-ART Considerations 23 January, 2007 Royce C. Lin, MD Assistant Clinical Professor of Medicine University of California, San Francisco Director, AIDS Consult Service San Francisco General Hospital Deputy Director, ASPIRE Positive Health Program, SFGH

2. GOALS Overview: Pre-ART considerations Overview: Pre-ART considerations Medical indications Medical indications WHO guidelines WHO guidelines Kenyan national guidelines Kenyan national guidelines US DHHS guidelines US DHHS guidelines WHO Staging system WHO Staging system Cotrimoxazole prophylaxis Cotrimoxazole prophylaxis Adherence issues Adherence issues

3. Pre-ART considerations: US Initial Visit F/U Visit HAART F/U Visit Full HPI, PMH Full Lab Counseling (tx, support) Establish relationship Adjunct services (social, insurance) Vaccinations Problem list, Px, Rx Follow CD4 decline Prep ART as CD4 <350 Choose regimen with pt input Adherence counseling/support Monitor toxicity Therapy switch as needed

4. Pre-ART considerations: RLS Initial Visit F/U visit HAART F/U Visit HPI, PMH (form/algorithm driven) Select Labs (baseline + ?TB, preg) WHO staging (triage ART) Counseling (x 3. Peer groups support) Adjunct services (nutrition, HBC) Cotrimoxazole Problem list, Px, Rx (algorithm-driven) See CD4 result With WHO, assess ART eligibility Adherence counseling x 3 if ART Cotrimoxazole, other prevention All get Triomune, unless contraindication Pregnancy? TB? Monitor toxicity (TB, preg, IRIS) Therapy switch as needed

5. When to Start HAART?

6.  All who have a CD4+ count ≤ 200 cells/mm 3, regardless of stage of illness  All who are in WHO stage IV clinical criteria, regardless of CD4+ cell count  Consider those who are in WHO Stage III clinical criteria and have CD4 cell counts ≤ 350/mm 3 Note! The patient must have expressed willingness and be ready to start therapy When to Start Therapy in adults Kenyan Guidelines

8. U.S. DHHS Guidelines Summary: ART recommended for… All with history of AIDS-defining illness, regardless of CD4 count All with history of AIDS-defining illness, regardless of CD4 count All with CD4<200 All with CD4<200 CD4 201-350 should be offered therapy CD4 201-350 should be offered therapy CD4>350 CD4>350 Most clinicians defer therapy regardless of VL Most clinicians defer therapy regardless of VL Some offer therapy if VL>100,000 Some offer therapy if VL>100,000

9. Perform WHO clinical staging Confirmed HIV + Individual WHO Clinical Stage 1 WHO Clinical Stage 2 WHO Clinical Stage 3 WHO Clinical Stage 4 Perform CD4+ T cell count Eligible for ART regardless of CD4 count CD4: <200 cells/mm 3 Do NOT initiative ART. Monitor patient regularly CD4: 200-350 cells/mm 3 CD4: >350 cells/mm 3 Eligible for ART regardless WHO Clinical stage Consider ART ONLY if in WHO clinical stage III

10. WHO Clinical Staging

13. WHO Clinical Staging System for Adults and Adolescents

15. Stage I Asymptomatic

16. Stage II Not yet AIDS, but getting sick CD4 usually 200-350

19. Courtesy of Jackie Dolev, M.D. Department of Dermatology University of California, San Francisco

20. www.uptodate.com

23. Prurigo

25. Herpes Zoster-Shingles

26. Stage III Early AIDS CD4 usually <200

32. Stage III Pulmonary TB Severe bacterial infections Bacterial pneumonia Pyomyositis Performance scale 3 Bedridden <50% in past month

33. Stage IV Late AIDS CD4 usually < 50-100

41. Other Stage IV Extrapulmonary TB Cryptococcal Meningitis Toxoplasmosis Esophoegeal candidiasis MAC CMV Retinitis HSV in mucocutaneous site Progressive Multifocal Leukoencephalopathy AIDS Dementia Complex Weight loss >10% and bedbound >50%

42. PSYCHOSOCIAL Contraindications OI Adherence? clinical signs Family and support? CD4 MEDICAL Indications Substance abuse

43. Who should get ART first? A. Female University Student A. Female University Student CD4 178. Thrush. Treated with clotrimazole CD4 178. Thrush. Treated with clotrimazole Family knows and is supportive Family knows and is supportive B. Successful Businessman B. Successful Businessman CD4 168. Very high VL (>500,000) CD4 168. Very high VL (>500,000) Diagnosed 1 week, anxious, demands immediate ART. Reluctant to disclose to spouse. Diagnosed 1 week, anxious, demands immediate ART. Reluctant to disclose to spouse. C. Disbelieving Rural Woman C. Disbelieving Rural Woman CD4 47. Bacterial pneumonia. Cutaneous KS CD4 47. Bacterial pneumonia. Cutaneous KS Skeptical about her AIDS diagnosis. Skeptical about her AIDS diagnosis.

44. When to Start: PART II Medical consideration only half of the equation Medical consideration only half of the equation Patient readiness EQUALLY important Patient readiness EQUALLY important Therapy quickly FAILS if suboptimal adherence Therapy quickly FAILS if suboptimal adherence >95% Adherence needed! >95% Adherence needed! Especially important with Triomune! Especially important with Triomune! Once first-line fails, second-line agents may not be effective and are more toxic Once first-line fails, second-line agents may not be effective and are more toxic BETTER TO WAIT AND START WHEN PATIENT IS TRULY READY BETTER TO WAIT AND START WHEN PATIENT IS TRULY READY

45. Adherence A major determinant of degree and duration of viral suppression A major determinant of degree and duration of viral suppression Poor adherence associated with virologic failure Poor adherence associated with virologic failure What percentage adherence is most strongly-associated with emergence of viral resistance? What percentage adherence is most strongly-associated with emergence of viral resistance? Optimal suppression requires 90- 95% adherence Optimal suppression requires 90- 95% adherence Even MORE important in resource-limited settings given lack of access to resistance testing, limited salvage options Even MORE important in resource-limited settings given lack of access to resistance testing, limited salvage options Suboptimal adherence is common Suboptimal adherence is common

46. Predictors of Inadequate Adherence Poor clinician-patient relationship Poor clinician-patient relationship Active drug use or alcoholism Active drug use or alcoholism Unstable housing Unstable housing Mental illness (especially depression) Mental illness (especially depression) Major life crises Major life crises Lack of patient education Lack of patient education Lack of patient access to medical care Lack of patient access to medical care Medication adverse effects Medication adverse effects Fear of medication adverse effects Fear of medication adverse effects

47. Predictors of Good Adherence Emotional and practical supports Emotional and practical supports Family, friends, social support Family, friends, social support Importance of social work, CBOs Importance of social work, CBOs Understanding the importance of adherence Understanding the importance of adherence Belief in efficacy of medications Belief in efficacy of medications Keeping clinic appointments Keeping clinic appointments Feeling comfortable taking medications in front of others Feeling comfortable taking medications in front of others Convenience of regimen Convenience of regimen Consideration of patient preferences in constructing an antiretroviral regimen Consideration of patient preferences in constructing an antiretroviral regimen

48. Predictors of Inadequate Adherence Age, race, sex, educational level, socioeconomic status, and a past history of alcoholism or drug use do NOT reliably predict suboptimal adherence. Age, race, sex, educational level, socioeconomic status, and a past history of alcoholism or drug use do NOT reliably predict suboptimal adherence. Higher socioeconomic status and higher education levels and lack of history of drug use do NOT reliably predict optimal adherence. Higher socioeconomic status and higher education levels and lack of history of drug use do NOT reliably predict optimal adherence.

49. Practicum: Case Discussions

50. Case scenario #1 35 yo woman from Kisumu 35 yo woman from Kisumu Tested HIV+ recently Tested HIV+ recently Comes to you for first visit in clinic Comes to you for first visit in clinic Wants to know what she should do Wants to know what she should do Physically well, no symptoms Physically well, no symptoms Baseline weight 68kg. Now 66kg. Baseline weight 68kg. Now 66kg. What WHO clinical stage is she? What WHO clinical stage is she? What else do you want to know? What else do you want to know? What do you want to do today? What do you want to do today?

51. Case scenario #1 1 year later, pt presents to casualty with 1 month hx of dry, non-productive cough. 1 year later, pt presents to casualty with 1 month hx of dry, non-productive cough. Hx: Increasing shortness of breath Hx: Increasing shortness of breath Scant sputum. No hemoptysis Scant sputum. No hemoptysis Weight: 59kg RR 32 Weight: 59kg RR 32 CXR: diffuse, patchy bilateral infiltrates. CXR: diffuse, patchy bilateral infiltrates. Exam: Diffuse rales, L>R. Oral thrush Exam: Diffuse rales, L>R. Oral thrush Pt is admitted to the ward Pt is admitted to the ward Has his clinical stage changed? Has his clinical stage changed? What stage do you guess him to be in now? What stage do you guess him to be in now? What do you want to do now? What do you want to do now?

52. Case Scenario #1 Hospital course Hospital course Sputum x 3: smear negative for AFB Sputum x 3: smear negative for AFB Started empirically on amoxicillin without improvement. Started empirically on amoxicillin without improvement. TMP/SMX begun (for presumed PCP) TMP/SMX begun (for presumed PCP) 5-days later: decreased SOB, cough 5-days later: decreased SOB, cough Discharged. Complete Rx at home Discharged. Complete Rx at home 5 days later (day#10 rx) 5 days later (day#10 rx) Seen in clinic Seen in clinic Still on PCP treatment. Finished amoxicillin Still on PCP treatment. Finished amoxicillin CD4 comes back: 178 CD4 comes back: 178 Feeling much better, slight residual cough Feeling much better, slight residual cough Weight 57kg. RR 18. Rales resolved. Weight 57kg. RR 18. Rales resolved. When do you want to start ART? When do you want to start ART?

53. Case Scenario #1 Who wants to start ART today? Who wants to start ART today? Does he meet medical indications to start ART? Does he meet medical indications to start ART? By which criteria? By which criteria? What are other considerations? What are other considerations? What would you do at this visit? What would you do at this visit? When is the optimal time to start ART? When is the optimal time to start ART?

54. Teaching points Wait until OI is treated Wait until OI is treated Increased overlapping toxicity Increased overlapping toxicity Increased risk of immune reconstitution syndrome Increased risk of immune reconstitution syndrome Prepare patient for ART Prepare patient for ART Assess psychosocial readiness Assess psychosocial readiness Establish relationship Establish relationship Involve entire care team Involve entire care team Good preparation = Successful therapy Good preparation = Successful therapy

55. Summary Medical Indications Medical Indications Any AIDS-defining condition Any AIDS-defining condition Any OI Any OI WHO Stage IV WHO Stage IV CD4<200 CD4<200 WHO, US guidelines agree WHO, US guidelines agree Psychosocial contraindications Psychosocial contraindications Factors of adherence Factors of adherence Belief systems Belief systems Role of social work, CBO, support Role of social work, CBO, support Balance between the two determines when to start ART Balance between the two determines when to start ART Careful consideration of both sides of equation leads to optimal chance at successful suppression of HIV. Careful consideration of both sides of equation leads to optimal chance at successful suppression of HIV.