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  • operational
  • Input as we prepare to present in Geneva, prepare a manuscript
  • Why not translated to practiceA key means to achieve this goal is ensuring that all HIV-infected TB patients receive antiretroviral therapy (ART), an intervention proven to markedly decrease mortality (WHO 2010). While WHO strongly recommends starting ART as soon as possible in all HIV-positive TB patients (WHO 2012), only 46% began ART in 2010 (WHO 2011).Low ART coverage is related in part to barriers TB patients face when they are referred to a specialized HIV clinic. A 2007 survey of eight high-burden countries found that ART services are much more centralized than TB treatment; there was one ART facility for every five health facilities where TB treatment was available (WHO 2009).
  • PIC form the search criteria:Had to have a comparator
  • PICO formed inclusion criteriaHad to have a comparator
  • I on left, C on RShow you models of care, comparisons the studies made, then the measures of effect
  • TBclnics more decentralizedDirectly address PICO
  • Comparator becomes the intervention!Bottom row: Not exactly what the PIC was asking therefore indirect
  • Comparator becomes the intervention!Bottom row: Not exactly what the PIC was asking therefore indirect
  • Statistically significant results only (CI quite wide for some—imprecision we’ll talk about soon)Estiamtes of effect: Intervention v. comparatorCouldn’t combine estimatesPublication bias?
  • Indirectness: pop (applicability),intervnetion, outcome (surrogate not pt important), lack of head to head comparisonAfter vs. before:New guidelines to start ART at higher CD4 counts. Just 2 points in time, what was trend before? Interrupted time seriesPackage of interventionsOther bias: eligibilty criteria to select exposed, unexposedFlawed measures of E, O (differential surveillance)Incomplete f/up
  • In HIV positive: directly relevant to PICO populationLess compelling outcome: many other factors feed in We don’t need to prove ART works to decrease mortalityFocus on more proximate measure of service deliverY: timely art uptakeSeveral authors commented on no worsening in treatment outcomes for all tB pts, or for HIV neg as evidence that already overburdened services did not get worse when they took on ART
  • TB clinics providing ARTHIV clinics providing TB diagnosis/treatment
  • No studies where TB diagnosis at HIV clinic compared to referral for dx in TB clinicLonger list of outcomes we hoped to find, but will present
  • Other interventions: new evidence Hermansatrributes to ART shortage during which clinicians appropriate prioritzation of TB pats withlower CD4 counts
  • One person, 2 diseases
  • Rather than label services integrated, describe the actual model
  • Job satisfaction, better patient care: TB pt’s ART regimen is changed to EFV
  • Royce

    1. 1. ART scale up – where are we now? <350 CD4 but not on ART <200 CD4 but not on ART 54% 6%Slide from Tony Harries, Strategic Use of ARVs, IAC Satellite, 7/22/2012
    2. 2. Scenarios for the incremental expansion of ARV provision to treat and prevent HIV Slide from Tony Harries, Strategic Use of ARVs, IAC Satellite, 7/22/2012
    3. 3. WHO Consolidated ART Guidelines Expanded Guidance Clinical, programmatic, operational Addressing all ages and Adults, women, children, MSM, IVDU, populations sex workers, prisoners Guidance across HIV testing, eligibility for ART, pre- continuum of HIV care ART care, ART care, ART retention Expanded evidence-base Systematic reviews, modelling, cost- effectiveness Public health approach Universal access and prioritizationSlide from Tony Harries, Strategic Use of ARVs, International AIDS Conference SUSA40, 7/22/2012 4
    4. 4. Systematic review of TB/HIV service delivery for WHO guidelines on antiretroviral therapy (ART) September 19, 2012 Sarah Royce, MD, MPH Assistant Clinical Professor Department of Epidemiology and Biostatistics Global Health Sciences 5
    5. 5. Overview• Introduction• WHO’s questions: – TB clinics providing ART – HIV clinics providing TB diagnosis/treatment• Methods: GRADE• Results 6
    6. 6. • 34 million people living with HIV• 350,000 dying with TBWHO estimates for 2010 7
    7. 7. • Strong WHO recommendations to start ART – In all HIV+ TB patients, regardless of CD4 count – Start TB treatment first, followed by ART as soon as possible within the first 8 weeks – Immediately within the first 2 weeks if CD4 count < 50 cells mm3• Less than half (46%) of the world’s HIV-positive TB patients in 2010 were known to begin ART 8
    8. 8. PICO-4a• Population: HIV+ TB patients• Intervention: ART provided at the TB clinic along with TB treatment• Comparator: referring HIV+ TB patients for ART to specialized HIV clinics• Outcomes: important to the patient 9
    9. 9. Outcomes• ART uptake• Timeliness of ART initiation• Adherence, retention on ART• TB treatment outcomes: success, death, loss to follow-up• Response to ART: – Immune recovery, viral suppression – AIDS-defining illnesses, IRIS• Cost• Clinical skills of staff 10
    10. 10. • Grading of Recommendations Assessment, Development and Evaluation• Transparent, structured process for – Developing and presenting summaries of evidence – Making recommendations for guidelines on alternative management approaches 11
    11. 11. • Frame the question• Chose outcomes of interest, rate importance• Generate estimate of effect for each outcome• Rate the quality of evidence for each outcome• Develop strong or weak recommendations based on quality of evidence, balance of (un)desirable outcomes, values and preferences• Consider resource use 12
    12. 12. Search results• Found 461 articles• Conference abstracts, contacted authors• Included – 9 full text articles – 13 conference abstracts from – Africa (19 studies in 13 countries) – Latin America (3 studies in 3 countries) 13
    13. 13. PICO 4a. Does ART provided with TBtreatment at the TB clinic result inbetter outcomes than referring HIVpositive TB patients for ART inspecialized HIV clinics? HIV TB TBI: Provides ART C: Refers for ART 14
    14. 14. After vs. Before TBProvides ARTKambale, Pevzner, Howard, van Rie HIV TB TB/HIV Refers for ARTSame nurse providesTB treatment and ARTBrown, Bygrave 15
    15. 15. After vs Before HIV TBHIV TB TB staff Refers for ART provides ART Chifundo, Huerga, Morse, Mugo, Phiri 16
    16. 16. After vs. Before HIV TB HIV TB TB staff Refers for ART provides ART Chifundo, Huerga, Morse, Mugo, Phiri Co-located vs. Geographically separate HIV TB HIV TB Dube, Ikeda, Kaplan, Louwagie, Muvuma, 17Schwartz
    17. 17. Outcome: ART uptake• After vs. before the TB (or TB/HIV) clinic began providing ART. Relative Risks (RR) – Improved in 8 studies (RR ranged from 1.2 to 4.8) – Worse (RR 0.9) in 1 study• Co-located vs. geographically separated TB and HIV clinics (during same period) – Improved in 2 studies (RR 2.5, RR 8.8) – No difference in 2 studies 18
    18. 18. Very low quality of evidence for improvement in ART uptake• Little confidence in measures of effect• Observational studies start as low• Downgraded for – Indirectness: geographically co-located (different I), referral within facility (different C) – Risk of bias: no adjustment for confounding (other interventions between “after” and “before,” patient characteristics) – Imprecision: small numbers of patients 19
    19. 19. HIV+ patients HIV+ TB patientsin care at HIV clinic; vs. referred from TBfound to have TB; Clinics to specializedstart ART HIV clinic to start ARTand TB treatment TB HIV TB Referrals for ARTLawn 20
    20. 20. Outcome: Timeliness of ART initiation• Estimates of effect (since start of TB treatment) – I: HIV clinic providing TB treatment (RR 4.9 in 1st month for TB patients with CD4 counts <50 cells) – C: referral in same facility (RR 2.2 in 1st 2 mos) – I: referral to co-located clinic (no difference in 1st 2 mos of TB treatment)• Very low quality of evidence – Indirectness in all 3 studies – Risk of bias: new policy to start ART early in 1 study – Imprecision in 1 study 21
    21. 21. TB treatment outcomes in HIV+ TB patients• Estimates of effect (# studies) – Improved (2), no change (4) – Worse in 1 (except no difference in failure)• Very low quality of evidence – Indirectness – Risk of bias: no adjustment for ART, CD4 count, differential follow-up – Imprecision• Utility as an effect measure? 22
    22. 22. Summary (# of studies)Very low quality evidence suggests that whenTB clinics provide ART, – ART uptake improved (10), no change (2), lower (1) – Timeliness of ART initiation improved (2), no change (1) – TB treatment outcomes in HIV+ improved (2), no change (4), worse (1) 23
    23. 23. 2012 WHO guidelines A. Deliver integrated TB and HIV services B. Reduce burden of TB in people living with HIV --intensified TB case finding C. Reduce burden of HIV in patients with TB --ART 24
    24. 24. PICO 4b. Does TB diagnosis and/or TBtreatment at specialized HIV clinics resultin better outcomes than referring HIV-positive patients to TB clinics for TBdiagnosis and/or treatment? HIV HIV TBTreat and/or Refer for TB treatmentdiagnose TB and/or diagnosis 25
    25. 25. 159 HIV sites vs. 22 HIV sites that referthat treat TB HIV HIV TB Treat TB Refer for TB treatmentHoward, 6 countries in Africa: Higher proportion ofscreened for TB (RR 1.4). Very low quality (bias) 26
    26. 26. After vs. Before TB/HIV HIV TBSame nurse diagnoses Refers for TB diagnosisTB,* provides TB treatment*”Mobile doctor” diagnoses and treatmentextrapulmonary TBBrown (S Africa): Increased % of extrapulmonary TBcases among all HIV-positive TB cases (RR 1.5). Verylow quality (inadequate adjustment for confounding) 27
    27. 27. After creation of TB/HIV unit vs. Before HIV HIV TB/HIV TB Refers for TB treatmentHermans (Uganda): Higher % starting ART during TBtreatment intensive phase (RR 2.6). Very low quality(imprecision, indirectness, confounding) 28
    28. 28. Outcome: ART uptake• Measures of effect – Improved (RR 2.2) comparing nurse-run “one stop shop” with referral to separate facility for TB treatment – Worse (RR 0.9) comparing TB/HIV unit to TB clinic referral (both within HIV service)• Very low quality of evidence – Indirectness – Risk of bias: confounding – Imprecision 29
    29. 29. HIV team visits Patient travels patient’s home to to TB clinic for provide TB vs. TB treatment treatment TBBento,* Cerda*organization of TB and HIV services in outpatient department is not specified 30
    30. 30. TB treatment outcomes in HIV+ TB patients• Hermans – On ART--no difference – Not on ART-- improved• Home TB treatment—mixedVery low quality of evidence: indirectness, bias (confounding, differential ascertainment of death), imprecision 31
    31. 31. Summary (# of studies)Very low quality evidence suggests that whenHIV services provide TB treatment, – TB screening and diagnosis improved (2) – ART uptake improved (1), decreased but was more timely (1) – TB treatment outcomes in HIV+ (3 studies with mixed results) 32
    32. 32. Executive Director, UNAIDS 33
    33. 33. Possible advantages of integration (Uyei, 2011)• Efficiency, share scarce resources, strengthen health system• Point of entry to early diagnosis, treatment, other services• Facilitates joint careTB services more decentralized than HIV services: 1 ART facility for every 5 health facilities where TB treatment was available (2007 WHO survey of 8 high-burden countries) 34
    34. 34. Considerations• Patient: costs and other barriers (time, stigma)• Healthcare worker: cross training, management of 2 diseases, volume/experience, task shifting to less specialized cadres• System: primary care vs. district hospital, urban/rural, record keeping, infection control, community involvement• Epidemiology: concentrated vs. generalized HIV epidemic 35