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No One Left Behind: HIV and Tuberculosis co-infection

No One Left Behind: HIV and Tuberculosis co-infection . Diane Havlir, University of California, San Francisco . Thank you to my co-authors . Mark Harrington. Soumya Swaminathan. Haileyesus Getahun . In 2014… We have . Evidence based prevention for HIV/TB New TB diagnostics

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No One Left Behind: HIV and Tuberculosis co-infection

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  1. No One Left Behind: HIV and Tuberculosis co-infection • Diane Havlir, University of California, San Francisco • Thank you to my co-authors • Mark Harrington • Soumya Swaminathan • Haileyesus Getahun

  2. In 2014… We have • Evidence based prevention for HIV/TB • New TB diagnostics • Ability to cure most TB in 6 months and to reduce mortality with ART • Over 1 million new TB cases in HIV+ persons and 320,000 HIV/TB deaths EVERY YEAR

  3. Why do we still have so much death and suffering from TB in the HIV epidemic? • We are not maximally implementing evidence based interventions • Most at risk populations (MARPS) for HIV/TB have not received adequate attention • Our care delivery is often disease (ie HIV or TB ) and NOT patient centric

  4. 2004: HIV/TB rampant overwhelming communities and health systems • Rapid, unabated increase in TB caseload due to HIV/TB interaction • TB risk increase 12-20 fold in HIV+ • Karim, Lancet, 2009

  5. 2014: Policy, advocacy and implementation have produced results • Over 40% decline in HIV/TB deaths and over 1.3 million lives saved • Diagnose and treat TB • Diagnose and treat HIV Source: Global tuberculosis report 2013. Geneva, World Health Organization, 2013 .

  6. Moving forward in 2014: Combination Prevention for HIV/TB • ART: 65% reduction in TB(1) • ART + isoniazid preventive therapy (IPT) additional 35% reduction in TB in high TB transmission areas(2) • NO TB SKIN TEST NEEDED • Transmission reduction strategies • Enhanced case finding (3) • Infection control • ART • IPT • Transmission reduction strategies • Combination Prevention • 1. Suthar, PLOS Medicine , 2012; 2. Rangaka, Lancet, 2014 3. Lorent PLOS One, 2014

  7. 2014: New and better diagnostics • XPERT MTBRIF: 2 hour molecular test for M.TB diagnosis and rifampin resistance(1) • More sensitive than AFB smear • Works in children and extrapulmonary TB • Screen for MDR and XDRTB • LAM: POC urine test(2) • 85% TB cases detected in HIV+ persons with < 100 CD4+ cells entering hospital with new TB diagnosis • 1. Lawn, Lancet ID, 2013 ;2. Lawn, CROI, 2014

  8. 2014: Treatment strategy of immediate TB therapy +early ART (2 vs 8 weeks) that saves lives and reduces HIV complications CAMELIA (Cambodia) SAPIT (South Africa) STRIDE (multicontinent)

  9. WHO 2010 ART Guidelines WHO Policy– Harmonized to optimize outcomes in HIV and TB • Start ART at CD4 <500 • Provide IPT for HIV-positive patients without active TB • For those with TB, ART initiated as soon as possible after the start of TB treatment • At 2 weeks when CD4<50; no later than 8 weeks • Prevent and Treat HIV and Prevent TB • Reduce HIV/TB deaths • And HIV morbidity

  10. Stepping up the pace requires we: • Understand who is dying and why they are dying • Adapt care delivery systems so we can apply the evidence • Pay more attention to HIV/TB MARPs • Invest in research to improve prevention, diagnosis and treatment of TB and HIV/TB

  11. Who is dying from HIV/TB? • TOP 10 COUNTRIES WITH HIV/TB DEATHS • South Africa 88,000 • Mozambique 45,000 • India 42,000 • Nigeria 19,000 • Zimbabwe 18,000 • Uganda 9,200 • Kenya 7,700 • Tanzania 7,000 • DRC 6,300 • Ethiopia 5,600 • Global TB report, 2012 data

  12. TOP 8 COUNTRIES WHERE ELIMINATION OF HIV/TB DEATHS IS WITHIN REACH • Cambodia 560 • China 1,200 • Russia 1,800 • Indonesia 2100 • Viet Nam 2100 • Thailand 2200 • Brazil 2500 • Myamar 4600 • Global TB report, 2012 data, high burden countries

  13. Reasons for HIV/TB Deaths • Some reasons for HIV/TB Deaths • HIV not diagnosed • TB not diagnosed • TB not treated • HIV not promptly treated • MDRTB • TB not recognized • (until autopsy) • CROI, 2013

  14. HIV is not diagnosed in TB; ART cannot be started • Globally, Only 40% TB cases HIV status known • Global TB report, 2012

  15. ART start lags behind guidelines • Malawi Program Data – before and after new 2011 country guidelines (1) • 685 HIV/TB cases • ART at any time increased from 70% to 78% • ART within 2 weeks increased from 30% to 46% • Best case scenarios: Less than half patients receiving ART in timely way to reduce mortality • Time to ART start not routinely collected in country programs • 1. Tweya, BMC Public Health, 2014, 2014

  16. Stepping up the pace requires we: • Understand who is dying and why they are dying • Adapt care delivery systems so we can apply the evidence • Pay more attention to HIV/TB MARPs • Invest in research to improve prevention, diagnosis and treatment of TB and HIV/TB

  17. The HIV/TB Care Cascade needs to be monitored and fixed • Undiagnosed TB • late ART start • bad care • Complete • TB • treatment • Active TB • Start ART • 2 weeks • Diagnose • TB • Treat • TB • Transition • to HIV care

  18. What is the best model for HIV/TB care? • The one that is convenient for the patient and delivers quality care • There is no one size fits all • Will vary according to HIV and TB prevalence • Possible HIV/TB clinic models • Referral models- 2 separate clinics • Integrated and co-located models • Considerations • Integrated models are optimal but require more effort on staff training and considerations such as infection control • Co-location not sufficient for optimal delivery of care • Most systems are still burdensome to the patient • Legidor Quigley, Trop Med Int Health, 2013; Schwartz, IJTLD, 2013; Uyei, Health Policy and Planning, 2014

  19. Adapting Care: Xpert MTB/Rif for Faster TB detection • Nurses coordinated Xpert use • Time to TB diagnosis less with Xpert and smear vs TB culture • More TB cases detected from Xpert vs smear • Time to TB treatment reduced with Xpert • We now need to overcome logistical challenges of Xpert scale up • Theron, Lancet, 2013

  20. Adapting Care: Increase in HIV testing in TB patients in India • Challenge: HIV testing in low prevalence setting

  21. Adapting Care: Isoniazid preventive therapy (IPT) in Brazil Globally, Only 1/3 patients in HIV care prescribed IPT (1) • THRIO Goal: increase IPT uptake for among HIV+ persons • 12,816 persons in 29 HIV clinics in Rio de Janeiro • Intervention • Operational training on TB skin test and IPT • Active TB screening within ART program • Supply chain fortification • 27% reduction in TB; 31% reduction in TB or death during the intervention period • 1. Global TB report, 2012; 2. Durovni, Lancet ID 2013

  22. Stepping up the pace requires we: • Understand who is dying and why they are dying • Adapt care delivery systems so we can apply the evidence • Develop strategies for HIV/TB MARPs • Children • Miners and their families and contacts • Persons who inject drugs (PWID) • Incarcerated populations • Invest in research to improve prevention, diagnosis and treatment of TB and HIV/TB

  23. Children– Left Behind • Children have more rapid progression of TB from infection to disease vs adults • TB diagnosis is more difficult in children than adults • TB/ART dosing and dose adjustments are more complex • Cascade of care even more challenging for children • 530,000 TB cases; 78,000 deaths in children* • *WHO estimate; Recent estimates by Dodd,( Lancet 2014 ) 650,000;Jenkins, (Lancet, 2014) 1 million

  24. Children– Some sobering data • High TB Burden and Mortality • 32% HIV + children enrolled in Malawi cohort 2004-2010 diagnosed with TB • 20% with TB died • 8.8 fold increase in death in those not starting ART vs those starting ART within 2 months • Broken care cascade • 1713 children presented with cough >2 weeks duration in rural Uganda clinics • Only 17.5% referred for microscopy • Among those found to be AFB smear positive, only approximately half started TB therapy • Buck, IJTLD, 2013 • Marquez, submitted

  25. Children– What Next? • Prevent all HIV transmission (MTCT B+) • Start ART in all children • IPT for all children exposed to TB cases • Childhood TB infection relevant to all of HIV/TB and TB control because much of global TB reservoir is established in childhood • Roadmap for Childhood tuberculosis – Towards Zero Deaths, WHO 2013

  26. Miners – “a public health catastrophe” • Extraordinary rates of TB 4000-7000/100,000 in miners vs general population in SSA • Second largest driver of TB in South Africa (after HIV) is mining • HIV and mining lethal combination • Silica exposure– increase risk 3 fold • HIV + increase risk greater than 10 fold • HIV + silica- exposure - increased risk 15 fold • Poor living conditions– increased risk many fold • All forms of TB are a problem • Latent TB- 89% in miners! • New TB infections and TB re-infections • MDRTB 3.6% (miners) vs 1.9% non miners • Dharmadadhikari, Int J Health Services, 2013

  27. Miners– What next? • Declaration on tuberculosis in the Mining Industry • Zero deaths from TB, Maputo, 2012 • Improved housing and mining conditions • HIV/TB prevention and screening as part of employee health contract • HIV testing • Offer ART start for all HIV+ persons (best TB prevention!) • Routine TB screening symptoms and radiograph • IPT (not just 6 months!) while in high risk setting • Continuity in care when miners come and go from employment • Xpert accessible for rapid diagnosis and identification of high risk for MDRTB

  28. Persons who inject drugs: intersection of HIV/TB/HCV • One third PWID are HIV-infected; two thirds are HCV infected • High rates of TB infection • Human rights violations drive PWID away from care • Getahun, Curr Opin HIV/AIDs, 2012; Grenfell Drug and Alcohol Dependence, 2013; Schluger, Drug and Alcohol Dependence, 2013

  29. Incarcerated Populations- Left Behind • High rates of incarceration exacerbate TB spread • 1/11 of TB transmission in prison on high income countries • 1/16 of TB transmissions in low and middle income countries • Crowded conditions • Limited health access • Declaration on tuberculosis for PWID or incarcerated populations • DOES NOT EXIST

  30. PWID and Prisoners -Next Steps • Improved housing • On-site HIV/TB prevention and screening • Routine HIV/TB screening • ART offered for all HIV+ • IPT (not just 6 months!) while in high risk setting • Opioid substitution therapy and compatible TB therapy/ART • Xpert accesible for rapid diagnosis and identification of high risk for MDRTB • Rapid ART start for new cases of TB in HIV+ patients • Getahun, Curr Opin HIV/AIDs, 2012; Grenfell Drug and Alcohol Dependence, 2013; Schluger, Drug and Alcohol Dependence, 2013

  31. Stepping up the pace requires we: • Understand who is dying and why they are dying • Adapt care delivery systems so we can apply the evidence • Pay more attention to HIV/TB MARPs • Invest in research to improve prevention, diagnosis and treatment of TB and HIV/TB • TAG TB Research and Development Report, 2013

  32. TB reservoir– it matters • What is TB reservoir? • Persistent infection with TB that can reactivate • HIV and aging both risk factors for this reservoir to develop into active disease • Why does it matter? • Estimated that 1/3 worlds population is infected with TB • Achilles heal of elimination of TB • Lung granulomas are dynamic and independent in metabolic activity and size • Lin, AAC, 2013

  33. Shorter TB prevention for ALL populations • Standard– Isoniazid 6-9 months • New 3 month regimen works! • INH/Rifapentine once per week – total 12 doses • Works in HIV+ population • Rifapentine can be administered with efavirenz • Even shorter- 1 month regimen under study Daily high dose INH + rifapentine (ACTG 5279) • We need to answer the question if even these more potent short course regimens work and are sufficient in high transmission settings. • Sterling, NEJM 2011: Sterling, CROI, 2014

  34. Shorter TB treatment • What do we want? Once daily, few pills, few side effects, compatible with ART, TB cures at 2 weeks, treatment for children • We cannot shorten TB treatment to 4 months with current drugs at standard doses • OFLOTUB study (gatifloxacin) • RIFAQUIN study (moxifloxacin/rifapentine ) • We cannot rely on the week 8 culture results to tell us if we need to extend treatment • Some of the TB agents in development interact with HIV medications and some are stalled in development • THE BAD NEWS

  35. The good news… (with more not so good news) • We may be able to combine available drugs using higher doses to shorten TB therapy • Rifapentine • Rifampin • We may be able to design regimens with new drugs that treat both drug sensitive and drug resistant TB TB Research and Development Investment • Reduced by 4.6% from 2011-2012 • Fell short of projected need in 2012 by over 1.2 billion USD

  36. Summary • HIV/TB rates are declining- but there are still over 1 million HIV/TB cases and 300,000 HIV/TB deaths • We need to deploy targeted strategic approaches , • Combination prevention for HIV/TB • New diagnostics • Rapid ART start • Stepping up the pace requires structural changes • Fix HIV/TB care cascade with a patient centric system • New HIV/TB MARPS programs- children, miners, PWID, prisoners • Research investment and renewed advocacy

  37. Conclusion “Every HIV/TB case is a public health failure” Helen Ayles, 2014 Every HIV/TB case prevented and every death averted is a public health success and puts us one step closer to ending the dual epidemic of HIV and TB Melbourne IAC, 2014 • WHO Post 2015 Strategy and Targets for TB; TB Elimination by 2035 • Endorsed by World Health Assembly, May 2014

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