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TB and HIV Treatment and Screening

TB and HIV Treatment and Screening. Santino Capocci. Incidence. Expressed as x/100PY (sometimes /1000 or 100 000) Cape Town Township 1.6/100PY SAfrica - Nationally 0.948/100PY Lesotho - 0.64/100PY Ethiopia - 0.3/100PY Somalia - 0.285. Bangladesh - 0.225 India - 0.168

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TB and HIV Treatment and Screening

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  1. TB and HIVTreatment and Screening Santino Capocci

  2. Incidence • Expressed as x/100PY (sometimes /1000 or 100 000) • Cape Town Township 1.6/100PY • SAfrica - Nationally 0.948/100PY • Lesotho - 0.64/100PY • Ethiopia - 0.3/100PY • Somalia - 0.285 • Bangladesh - 0.225 • India - 0.168 • Thailand - 0.137 • Russia - 0.106 • Brazil - 0.045 • England 1915 - 1.2/100PY • Newham - 0.108 • London - 0.0413 • Spain 0.017 • UK (National) 0.012 • US (National) 0.0041

  3. 9 million new cases of active TB each year • 12% HIV co-infection • 80% from sub-Saharan Africa or SE Asia • TB rate increased 2-3x in sSA • TB/HIV morbidity and economic cost huge but unknown • TB responsible for 25% of all HIV-related deaths

  4. WHO, 2011

  5. SAPIT - Oct 2011 • KwaZulu-Natal (CAPRISA), open label RCT • 642 patients with TB, CD4 <500 • ART ≤4 wks or at 2-3 months or after treatment (stopped) • AIDS or death 6.9 vs 7.8 /100PY overall; (death 12 in seq arm) • 8.5 vs 26.3 /100PY if CD4 <50 • IRIS: 20.1 vs 7.7/100PY

  6. STRIDE / ACTG A5221 Oct 2011 • Open label, randomised, CD4 <250 • ART ≤2 weeks or 8-12 weeks • Death or new ADI at 48 weeks • 661 patients • 16% early group vs 27% later group died or ADI if CD4<50 • IRIS 11% vs 5%

  7. CAMELIA - Oct 2011 • CAMbodian Early versus Late Introduction of Antivirals • 2 wk or 8 wk ART into TB treatment; CD4 <200 • 661 patients; 59/332 deaths (18%) early, 90/329 (27%) late • 8.28 /100PY in early, 13.77 / 100PY late group • No difference between CD4 <50 or 50-200 • IRIS rate: 3.76 early vs 1.53 / 100PY late (HR 2.5, P<0.001)

  8. BHIVA Guidance

  9. TB Meningitis - Török, 2011 • Randomised RCT, double blind, immediate vs deferred ART - at entry or 2 months • 253 patients in Vietnam • Treatment with efavirenz (800 od with Rif), zidovudine, lamivudine • All treated with TB meds, dexamethasone, cotrimoxazole. (3 months RHZE, then 6 months RH) Followed for 12 months Török, CID 2011;52:1374

  10. 127 immediately, 126 deferred • 76 died in immediate group, 70 in deferred within 9 months • Immediate ART not significantly associated with inc mortality (P0.31) • High severe adverse events in both arms (89% vs 90%), but more grade 4 in immediate arm • Conclusion - immediate ART does not improve outcome, more Gd 4 adverse events • Supports delayed initiation of ART in HIV associated TMB

  11. Sterling - After ART • Review of NA-Accord data from 16 centres • Risk of TB after starting ART - compared those at <3 months to those after 3 months • 19% IDU, median CD4 207 prior to ART • Risks quoted as 1.3 to 1.7/100PY • Risk factors for TB in first 3 months were:Black, Hispanic, IDU, ART naive, CD4 <200, high HIV VL.

  12. 0.4% diagnosed with TB after HAART initiation. • Risk not significantly different between 200-350 vs ≥350. • 64% of TB patients were TST positive; 39% had had IPT. • At 3 months, IR was 2.15/100PY vs 0.05 gen pop (50x) • Rate 8x that of gen pop, even after 5 yrs on ART.

  13. What is the aim of screening? • Low TB burden countries • Latent TB infection • Active TB disease • Subclinical TB disease • High TB burden countries • Active TB disease • Subclinical TB disease • Latent TB infection

  14. Antonucci JAMA1995;274:143 Badri Lancet 2002;359:2059

  15. Screening for Latent TB • In Southern Africa, 10-89% adults have evidence of latent tuberculosis infection • Active TB risk is increased 2-3x within first 2 years after seroconversion and rises

  16. Risk factors for active TB • Injecting drug user vs MSM • Heterosexual vs MSM • From TB endemic country • ? Reported previous TB • Advanced clinical stage of disease • Low blood CD4 count • Not on ART Badri. Lancet 2002;359:2059 Girardi. CID 2005;41:1772 Seyler. AJCCRM 2005;172:123

  17. NICE guidelines for screening

  18. BHIVA approach to LTBI • Balance risk of active TB developing • vs • Risk of drug induced hepatotoxicity* * Serious hepatotox estimated as 0.3%

  19. BHIVA guidelines for screening

  20. CHIC data • Collaborative HIV Cohort Study Group • Observational cohort of 27868 patients • Risk factors for TB were: low CD4 , ethnicity, high VL • Black African (RR 2.93) • TB incidence decreased after starting ART Grant, AIDS 2009: 23 2507

  21. SHCS Data 2007 • Swiss cohort data. Overall incidence was 0.2/100PY • 69% had TSTs, 9.4% positive. • 56 patients/6160 developed TB • 6.5% pos TST group dev TB, 0.26% neg TST group (Pos likelihood ratio 10.7) • NNT for IPT was 15 (8 high burden country) Elzi CID 2007 44:94-102

  22. LTBI Rx 144 No TB Active TB 142 No Rx 246 16 TB (6.5%) TST + 390 4168 TST 6160 TST - 3778 10 TB (0.26%) No TST 1850 30 TB

  23. Role of Isoniazid Preventative Therapy • Isoniazid 6-12 months reduced risk of active TB by 34% • TST +ve - 62% • TST -ve - 11% • Reduction in all cause mortality for Inh in TST+ or Inh/Rif • Countries inc USA, Spain, sSA • Usually benefit for 2-3 years Akolo, Cochrane Review, 2010

  24. After having TB…any role for IPT again? • South African gold miners • Secondary IPT prevented 55% further cases • NNT 5 and 19 if CD4 <200 or ≥200 • No ART Churchyard, AIDS 2003:, 17:2063-2070

  25. Role of ART • 9 observational cohort studies - reduction by 67% • ~80% (Brazil, USA, Italy) • Most benefit in those with low CD4 counts • Lifelong treatment (hence longterm benefit) Badri Lancet 2002 359 2059 Jones IJATLD 2000 4 1026 Girardi AIDS 2000 14:13, 1985

  26. Role of ART and IPT • 1 Brazilian study – 76% reduction in Rio on IPT and ART.Rates (TST+):IPT 1.6% No IPT 11.5% ART 2.8% No ART 5.5% • 1 SA study - 2 cohorts IPT alone reduced by 27%, ART alone 64%, Combined 89%CD4<100: 10.7/ 100PY TB Golub AIDS 2007 21 1441Golub AIDS 2009 23 631

  27. Martinson et al 2011, NEJM 365:11-20 • 4 groups, all pos TST • Rifapentine 900mg + Isoniazid 900mg weekly • Rifampicin 600mg + Isoniazid 900mg twice weekly • Isoniazid 300mg od for up to 9 years • Isoniazid 300mg od for 6 months

  28. Median CD4 484 • Rates of TB: • 3.1 R’pentine/Iso • 2.9 R’icine/Iso • 2.7 Isoniazid cont • 3.6 Isoniazid 6 months • None inferior to 6 months isoniazid.

  29. NICE guidelines for screening

  30. BHIVA guidelines for screening

  31. From 2000-2010, RFH treated 212 cases in total with TB/HIV co-infection • 140 not eligible for screening as presented with TB at HIV diagnosis

  32. Summary • Incidence of TB is lower on ART but higher than w/o HIV • Normal X ray and no symptoms ≠ no TB in HIV • Treat TB with ART immediately if CD4 <100, within 8 weeks if 100-350, maybe later if TBM • Screening recommended but not rolled out

  33. Questions?

  34. Not talked about: • Limits of TSTs and IGRAs in HIV • Use of IGRAs in detecting active disease in HIV • Drug interactions when treating it • IPT and ART in reducing the risk of reactivation of latent TB

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