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1. Thank you for viewing this presentation. • We would like to remind you that this material is the property of the author.It is provided to you by the ERS for your personal use only, as submitted by the author. • 2012 by the author

2. ERS School Course on TB and M/XDR-TB: from clinical management to control and elimination Session III: Treatment and clinical management TB/HIV management: what is new? Giovanni Sotgiu and GB Migliori Bucharest , Friday, 25 May 2012

3. TB/HIV co-infection Special thanks to: - Prof GB Migliori and Dr Alberto Matteelli (TBPANET-funded courses of Sondalo, Italy) - Dr Matteo Zignol (WHO office, Geneva, Switzerland) for having shared their ppt materials.

4. TB/HIV co-infection: outline • Epidemiology. • TB/HIV collaborative activities: • ICF; • IPT; • ARV therapy; • HIV testing; • CPT. • News from the scientific literature: • TB/HIV co-infection and IGRA testing; • TB/HIV co-infection and LAM urine assay.

5. Epidemiology Global burden of TB/HIV in 2010 Deaths Cases 0.4 million (range, 0.32–0.39 million) 1.1 million (13%) (range, 1.0–1.2 million) HIV-associated TB WHO. Global TB report 2011

6. M. tuberculosis First Infection Re-infection (exogenous) Primary TB Latent TB Reactivation (endogenous) Post-primary TB Progressive Primary TB Epidemiology Relative risk for TB: HIV neg. = < 10% per lifetime HIV pos. ~ 3-7 % per year HIV positive

7. Epidemiology Incidence of TB, 2010 Prevalence of HIV among new TB patients, 2010

8. Epidemiology Treatment outcomes for HIV-positive and HIV-negative TB patients, 2009. HIV-pos 72% VS. HIV-neg 88% Only 21% of the estimated global HIV-related TB cases (81 countries) WHO. Global TB report 2011

9. Epidemiology Treatment outcomes for HIV-positive and HIV-negative TB patients, 2009. HIV-pos 20% VS. HIV-neg 3% WHO. Global TB report 2011

10. Epidemiology 41 high TB/HIV burden countries, 2010 WHO. Global TB report 2011

11. Epidemiology

12. Epidemiology Survey on TB/HIV co-infection in EU/EEA member states Kruijshaar ME et al.EurRespir J 2011; 38.

13. Epidemiology Collection of HIV status in TB surveillance systems in EU/EEA member states Kruijshaar ME et al.EurRespir J 2011; 38.

14. Epidemiology Policies of HIV testing in EU/EEA member states Kruijshaar ME et al.EurRespir J 2011; 38.

15. Epidemiology TB/HIV co-infected patients in EU/EEA member states Kruijshaar ME et al.EurRespir J 2011; 38.

16. Epidemiology • Proportion of TB/HIV patients reported to the national surveillance systems is actually suboptimal (high variability in the EU/EEA). • Main obstacles: a) patient confidentiality; b) anonymous testing of HIV pts. • The majority of the member states recommend testing all TB pts for HIV. Kruijshaar ME et al.EurRespir J 2011; 38.

17. Epidemiology

18. Epidemiology • Systematic review of peer reviewed MS and‘‘grey literature’’ focused on TB–HIV co-infection prevalence and risk factors in EU/EEA. Kruijshaar ME et al.EurRespir J 2011; 38.

19. Epidemiology TB/HIV co-infection in EU/EEA member states Pimpin L et al.EurRespir J 2011; 38.

20. Epidemiology Trends of TB/HIV co-infection in EU/EEA member states Pimpin L et al.EurRespir J 2011; 38.

21. Epidemiology Socio-demographic characteristics of TB/HIV co-infected vs TB pts in EU/EEA Pimpin L et al.EurRespir J 2011; 38.

22. Epidemiology • Males, young adults, migrants, those living in urban areas, IVDUs, homeless and prisoners identified as high-risk groups for TB–HIV coinfection. Kruijshaar ME et al.EurRespir J 2011; 38.

23. TB/HIV collaborative activities WHO TB/HIV policy: from Interim to Definite 2004 2012

24. The Stop TB Strategy at a glance Raviglione MC et al.Lancet 2006; 367.

25. TB/HIV collaborative activities WHO. Interim Policy on Collaborative TB/HIV Activities. 2004.

26. TB/HIV collaborative activities A. Establish the mechanisms for integrated TB and HIV services 1. Set up or strengthen a TB/HIV coordinating body effective at all levels 2. Conduct HIV and TB surveillance among TB and HIV patients respectively 3. Carry out joint TB/HIV planning 4. Conduct monitoring and evaluation B. Decrease the burden of TB in PLHIV through earlier ART and Three Is for HIV/TB 5. Intensify TB case finding and ensure quality TB treatment 6. Introduce TB prevention with IPT and ART 7. Infection control for TB in health care and congregate settings ensured C. Decrease the burden of HIV in patients with presumptive anddiagnosed TB 8. Provide HIV testing & counselling to patients with presumptive and diagnosed TB 9. Introduce HIV preventive methods patients with presumptive and diagnosed TB 10. Provide CPT for TB patients living with HIV 11. Ensure HIV prevention, treatment & care for TB patients living with HIV 12. Provide Antiretroviral therapy to TB patients living with HIV WHO. Policy on Collaborative TB/HIV Activities. 2012.

27. TB/HIV collaborative activities WHO. Policy on Collaborative TB/HIV Activities. 2012.

28. TB/HIV collaborative activities TB DOTS +VCT +Condoms +HIV surveillance HIV VCT + TB screening IEC STIs ARVs TB/HIV Intensified case-finding Isoniazid preventive therapy Co-trimoxazole preventive therapy Home- and community-based care General health services

29. TB/HIV collaborative activities

30. TB/HIV collaborative activities • Some progress in HIV care for people with TB, with more TB patients being HIV tested, although too few receive ARTs and co-trimoxazole prophylaxis • Less progress on the "3Is": intensified case finding in community and facilities; infection control; and isoniazid preventive therapy

31. TB/HIV collaborative activities • Some progress in HIV care for people with TB, with more TB patients being HIV tested, although too few receive ARTs and co-trimoxazole prophylaxis • Less progress on the "3Is": intensified case finding in community and facilities; infection control; and isoniazid preventive therapy

32. TB/HIV collaborative activities • Intensified case finding in the community (door-to-door, mobile vans) and in health facilities using modern technology. • Infection control in health facilities: facility-level and administrative measures, environmental and personal protection. • Isoniazid preventive therapy, irrespective of degree of immune suppression and TST, but after careful screening to rule out active TB.

33. TB/HIV collaborative activities Intensified case finding (ICF) • Screening and diagnosing TB in people living with HIV can bechallenging. • ICF is a gatekeeperfor the other 2 I’s: itrapidlyidentifyies TB suspects (allowing triage and othermeasuresto reduce transmission) and allowsprovisionof IPT to PLWHA who don’t haveactive TB.

34. TB/HIV collaborative activities Intensified case finding (ICF) • Adults and adolescents living with HIV should be screened with a clinical algorithm and those who reportedone of the following: • current cough, • fever, • weight loss or • night sweats • may have active TB and should be evaluated for TB and other diseases. WHO. IPT/ ICF recommendations. 2011

35. TB/HIV collaborative activities Intensified case finding (ICF) • Presence of symptoms – work up for TB • Sensitivity 79% • Specificity 56% • Absence of symptoms – proceed with INH preventive therapy • Negative predictive value 97% (*) • (*) at a prevalence of TB of 5% Getahun H et al. Plos Med 2011; 8.

36. TB/HIV collaborative activities Intensified case finding (ICF) Getahun H et al. Plos Med 2011; 8.

37. TB/HIV collaborative activities Intensified case finding (ICF) The addition of abnormal findings on chest X-ray increases the sensitivity from 79% to 91%, but the negative predictive value only increases from 97.8% to 98.7%. The benefits of radiology increase with the increase of TB prevalence (significant for prevalence > 20%). WHO. IPT/ ICF recommendations. 2011

38. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) Isoniazid 300 mg /daily for 6-9 months WHO. IPT/ ICF recommendations. 2011

39. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) Incidence of TB Akolo C et al. Cochrane Review 2010.

40. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) • In areasof high prevalenceof TB (>30% infected): All HIV infectedindividualswho are notaffectedbyactive TB • In areasoflowerprevalenceof TB (<30% infected): HIV infectedindividualswith a positive PPD test who are notaffectedbyactive TB Independentlyfrom CD4 cellcount Akolo C et al. Cochrane Review 2010.

41. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) Balcells M et al. EID 2006.

42. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) Samandariet al., CROI Conference, San Francisco, 2010

43. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) rifapentine (900 mg) plus isoniazid (900 mg) weeklyfor 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twiceweeklyfor 12 weeks, isoniazid (300 mg) dailyfor up to 6 years (continuousisoniazid), isoniazid (300 mg) dailyfor 6 months (controlgroup) Martinson NA, N Engl J Med 2011, 365

44. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) Golub et al., AIDS 2007;21

45. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) South African Adults with HIV Infection * Adjusted for age, sex, CD4, prior history of TB, urban/rural Golub et al, AIDS 2009;23

46. TB/HIV collaborative activities Isoniazid Preventive Therapy (IPT) TB/HIV Working Group of the Partnership Focus on EuropeanRegion, Almaty, May 2010 • Thereis no study on the thresholdofresistancewhichmake IPT non more costeffective. • Evenwith 50% resistancetherewillbe 50% of the subjectswhowill benefit from IPT. • IPT recommended in EasternEurope and Central Asia, where INH resistanceishighest.

47. TB/HIV collaborative activities Anti-HIVtherapy • HAART reduces the incidenceof TB byapproximately 80% in high and low burdencountries. • HAART reducesby >50% the rate ofrecurrent TB aftercompletionof TB treatment. • HAART maybe key tocontrol MDR epidemicsamong HIV infectedpersons. • HAART mayunmask TB in personswith low CD4 cellcount. • TB incidence in HIV infectedpersonsreceivingeffective HAART is ~ 10 timeshigherthanthat in the background population.

48. TB/HIV collaborative activities Incidence of TB after initiation of HAART During the initial months of HAART incident TB cases may arise as a consequence of “unmasking” of previously subclinical disease or the deterioration of a pre-existing disease due to the reconstitution of the immune system (Lawn, 2005) Dembele M, Int J TubLungDis 2010, 14

49. TB/HIV collaborative activities Anti-TB treatment a Daily TB treatment is recommended in HIV-positive persons. b Direct observation of drug intake is recommended during the entire course of therapy, but particularly during the initial phase of treatment. c Streptomycin may be used instead of ethambutol. In meningeal TB, ethambutol should be replaced by streptomycin, which diffuses more in the meninges. d Whenever possible, drug sensitivity testing should be done to design standardized or individualized treatment regimen.

50. TB/HIV collaborative activities Anti-HIVtherapy Decrease morbidity and mortality related to HIV/AIDS WHO recommendation • Start ART in all HIV infected individuals with active tuberculosis irrespective of CD4 cell count (strong recommendation – Low quality of evidence) WHO, 2010: ART guidelines