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HIV and Tuberculosis: science and implementation to turn the tide and reduce death

HIV and Tuberculosis: science and implementation to turn the tide and reduce death. Anthony D Harries The “Union”, Paris, France London School of Hygiene & Tropical Medicine, UK. Global Data for 2010.

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HIV and Tuberculosis: science and implementation to turn the tide and reduce death

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  1. HIV and Tuberculosis: science and implementation to turn the tide and reduce death Anthony D Harries The “Union”, Paris, France London School of Hygiene & Tropical Medicine, UK
  2. Global Data for 2010 1.1 million people with HIV-TB 350,000 HIV-TB deaths WHO Global Tuberculosis Control 2011
  3. Over 80% of HIV-TB in sub-Saharan Africa WHO Global Tuberculosis Control 2011
  4. Number of people receiving antiretroviral therapy in low- and middle-income countries, by region, 2002–2010
  5. Of HIV-infected patients who start antiretroviral therapy (ART) in Africa 8% - 26% die in first year Often due to diagnosed and undiagnosed TB Lawn SD et al. AIDS 2008; 22: 1897 - 1908
  6. Autopsies in HIV-positive persons dying on medical wards in Africa 1 Lucas et al, BMJ 1994; 308: 1531-3. 2 Rana et al, JAIDS 2000; 24: 23-9. 3 Ansari et al, IJTLD 2002; 6: 55-63. 4 Cohen et al. PLoS Medicine 2010; 7: e1000296. 5 Wong et al, XVIII Int AIDS Conference 2010
  7. Mortality rates in HIV-infected smear-positive PTB patients before era of ART 1 Ackah et al, Lancet 1995; 345: 607-10; 2 Perriens et al, N Engl J Med 1995; 332: 779 – 84
  8. 2012
  9. Four spheres of work
  10. Prevent TB in persons with HIV: give early ART and IPT
  11. Effect of ART on TB Incidence Rates: systematic review and meta-analysis IRR 0.35 [0.28-0.44] for all baseline CD4 counts Adapted from Suthar AB et al, PLOS Medicine 2012; 9: e1001270
  12. Malawi: TB case notification and ART Zachariah et al, IJTLD 2011; 15: 933-7
  13. The current challenge in sub-Saharan Africa PLHIV start ART at CD4 cell counts of 100-150 cells/uL Most HIV-infected TB patients are diagnosed at CD4 cell counts of 150-200 cells/uL Thus, HIV diagnosis and ART are TOO LATE to prevent TB
  14. Early versus Standard ART in HIV-infected adults in Haiti[Severe P et al, NEJM 2010; 362: 257-265](Early = CD4 200-350; Standard= CD4<200 or AIDS 50% reduction in TB incidence 75% mortality reduction
  15. Early ART (CD4 350-500) versus Delayed ART (CD4 < 250) 96% reduced HIV transmission to HIV-negative partner 40% reduction in clinical events in HIV-infected persons – mainly related to EPTB (3 cases with early ART versus 17 with delayed ART)
  16. Mathematical models predict huge TB prevention benefit from early ART Universal HIV testing and immediate start of ART in PLHIV Lancet 2009 Granich et al, Lancet 2009; 373: 48-57 TB incidence reduced by 48% in 5 years TB incidence reduced by 98% in 40 years 6 Million TB cases averted in 40 years Proc Nat Acad Sci USA 2010
  17. Granich et al, 2011
  18. HIV-Infected HIV-Uninfected TB rate (per 100 PY) 0.62
  19. Isoniazid Preventive Therapy [IPT] Reduces overall TB risk by 33% Protective effect in those with positive tuberculin skin test (TST) where risk reduction is 64% (Akolo et al 2010) WHO Guidelines from 1998 – 2009 emphasised IPT in PLHIV with positive TST
  20. Challenges with scale up Process and assessment of TST Reliable exclusion of active TB WHO Global TB Report 2010
  21. WHO Guidance for IPT: PLHIV with unknown or positive TST and who do not have TB should receive IPT TST not a requirement for starting IPT IPT for 6 months (strong recommendation) IPT for 36 months (conditional recommendation)
  22. Botswana IPT Study Cumulative TB incidence in the in-trial & post-trial period by study arm for all participants Post-trial (no IPT) n=1678 6m v 36 m IPT in trial n=1995 P=0.52 P=0.04 Cumulative TB incidence 6H 6H 36H 36H 6H 36H Samandari et al, Lancet 2011; 377: 1588 – 1598; Samandari et al, CROI 2012
  23. Effect of IPT and ART in PLHIV 1 Golub et al, AIDS 2007; 21: 1441-8; 2 Golub et al, AIDS 2009; 23: 631-6 Await ANRS TEMPRANO (Cote d’Ivoire) & HAART-IPT (S Africa)
  24. CHILDREN Lower TB prevalence in HIV-infected children than adults[Lucas et al 1996; Chintu et al 2002; Ansari et al 2003] Early ART reduces infant mortality and risk of TB from 20% to 8% per year[Violari et al, NEJM 2008, 359, 2233-44] IPT with ART does not further reduce TB risk (11% v 14%) [Madhi et al, NEJM 2011, 365, 21-31]
  25. Find, diagnose and treat TB in persons with HIV
  26. Standard TB Symptom Screening Tool Cough – current and of any duration Unintentionalweight loss – in last 4 weeks Night sweats – in last 4 weeks Fever – in last 4 weeks Getahun H et al. PLoS Medicine 2011, 8: e1000391
  27. Usual way of investigating for Tuberculosis Smear microscopy and chest x-ray Time consuming – Costly - Tests are insensitive
  28. New TB diagnostic tools: Xpert MTB/Rif Sputum Specimen Other Specimen Sensitivities: Smear-positive PTB - 1 specimen = 98% Smear-negative PTB - 1 specimen = 72%; 3 specimens = 90% EPTB - different specimens = 81% (range 25% - 97%) Diagnosis in under 2 hours Boehme et al, N Engl J Med 2010; 363: 1005-15: Lawn and Zumla, Exp Rev Anti-Infect Ther 2012
  29. New TB diagnostic tools: Urine TB-LAM Urine LAM URINE SPECIMEN TB-LAM Dip-stick Determine TB-LAM test strips (diagnosis in 30 minutes) [specificity 98%: sensitivity increases as CD4 count declines (~66% at CD4 < 100 cells/uL] Lawn et al, Lancet Infect Dis 2011; Dorman et al, CROI 2012
  30. “Three I’s” in HIV care settings “TB diagnosis” Isoniazid Preventive Therapy (IPT) Intensified case finding (ICF) Infection Control (IC)
  31. Two trials to investigate this intervention: PROMPT (EDCTP) and REMEMBER (ACTG network)
  32. Diagnose and Treat HIV in TB
  33. Presumptive or diagnosed TB Provider initiated HIV testing and counselling [PITC] If HIV- seropositive Start cotrimoxazole preventive therapy as soon as possible [25% - 46% mortality reduction] Start antiretroviral therapy as soon as possible [64% - 95% mortality reduction]
  34. HIV Testing for TB patients, all countries 2003-2010 New and retreatment TB cases in blue TB cases HIV tested in green In 2010: Africa 59% Europe 80% WHO Global Tuberculosis Control 2011
  35. PITC for persons suspected of having TB and referral to HIV care and treatment Patients with suspected TB but negative sputum smears Zimbabwe: [12-month follow-up] 63% HIV-positive; 85% CD4 < 350 18% developed TB 12% died Only 15% were placed on ART MacPherson et al, IJTLD, 2011; 15: 1390-6
  36. WHO 2010 ART Guidelines All HIV-positive TB patients eligible for ART, regardless of CD4 count ART initiated as soon as possible after the start of TB treatment
  37. SAPIT CAMELIA STRIDE
  38. Key Message Camelia Study in Cambodia ART start within 2-4 weeks reduces death in HIV-positive PTB, especially with CD4 counts < 50/uL IRIS is more frequent in the early start ART group
  39. TB Meningitis Delay ART because IRIS within the central nervous system is dangerous Second line ART (PIs) RMP cannot be used Rifabutin (RFB) is safe and effective Need to reduce cost, work out optimum dosing schedules, introduce into FDC Two other ART-TB issues Loeliger et al, IJTLD 2011; 16: 6-15 Torok et al CID 2011, 52, 1374-83
  40. Drug-resistant Tuberculosis Gandhi et al, Am J Respir Crit Care Med 2010, 181: 80-6 ART and CPT: ART and CPT reduce mortality No RCTs done Same advice as for drug-sensitive TB
  41. Deliver HIV-TB services:health facilitiescommunity
  42. Health Facilities: co-location of TB and HIV clinics TB clinic ART clinic In clinics in separate geographical locations in South Africa, 11% of HIV-TB patients with CD4 < 50 started ART within 4 weeks of TB diagnosis Lawn et al, N Eng J Med 2012; 366: 474 Malawi - Salima District Hospital
  43. Health Facilities: integrated HIV-TB clinics
  44. Community HIV-Self Testing Men Women
  45. Community Case Finding and Prevention DETECTB Zimbabwe Cluster-randomised trial 46 clusters ~120,000 adults Zambia and South Africa Cluster-randomised trial 24 clusters ~ 962,000 people South Africa Gold miners Cluster-randomised trial 15 clusters ~78,596 people
  46. Community Multi-disease Campaigns Kenya (Lurambi) – HIV, malaria, diarrhoea
  47. BOLD VISION Three Zero’s by 2015: Zero new infections Zero discrimination Zero AIDS-deaths
  48. John Donne: “…any mans death diminishes me because I am involved in Mankinde; And therefore never send to know for whom the bell tolls; it tolls for thee….” Thanks to all who helped with the presentation Stephen Lawn Rony Zachariah Haileyesus Getahun Diane Havlir Taraz Samandari Elizabeth Corbett Helen Ayles Peter Godfrey-Faussett Eric Goemaere Reuben Granich Rod Escombe Gavin Churchyard
  49. Anthony D Harries, Stephen D Lawn, Haileyesus Getahun, Rony Zachariah and Diane V Havlir New Article HIV and tuberculosis – science and implementation to turn the tide and reduce deaths Harries AD et al. J Int AIDS Soc 2012, 15:17396 available at www.jiasociety.org
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