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TB and HIV Treatment and Screening Santino Capocci.

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Presentation on theme: "TB and HIV Treatment and Screening Santino Capocci."— Presentation transcript:

1 TB and HIV Treatment and Screening Santino Capocci

2 Incidence Expressed as x/100PY (sometimes /1000 or ) Cape Town Township 1.6/100PY SAfrica - Nationally 0.948/100PY Lesotho /100PY Ethiopia - 0.3/100PY Somalia Bangladesh India Thailand Russia Brazil Spain UK (National) US (National) England /100PY London Newham


4 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

5 WHO, 2011



8 StudyCountry Active TB prev Rate subclinical of infn Propn with symptoms Lawn SA17.3%18%75% Oni SA8.5%56% Mtei Tanz15%29-50%37%* Shah Ethiopia7%16%- SwaminathanIndia-4% total- Corbett 2001Zimb1.5%41%-

9 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

10 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%

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

12 BHIVA Guidance CD4 (cells/µL)When to start HAART <100As soon as practical As soon as practical, but can wait until after 2 monthsTB treatment >350Physicians discretion

13 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

14 127 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

15 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.

16 0.4% diagnosed with TB after HAART initiation. Risk not significantly different between vs ≥ % 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.

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

18 CD4 ItalySA TST+TST-No ARTART Incidence (100 PY) < ≥ Antonucci JAMA1995;274:143 Badri Lancet 2002;359:2059


20 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

21 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

22 NICE guidelines for screening

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

24 Sub-Saharan Africa Medium TB incidence country Low TB incidence country Blood IGRA+++ Blood CD4 count Any<500<350 Duration of ART use <24 months <6 months BHIVA guidelines for screening

25 CHIC data Collaborative HIV Cohort Study Group Observational cohort of 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:

26 CD4 Relative risk increase <

27 Origin Incidence (/100PY) Incidence if CD4 <50 Incidence if CD4 >500 sSA MI LI

28 Origin Incidence (/100PY) Incidence if CD4 <50 Incidence if CD4 >500 sSA MI LI

29 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 :94-102

30 6160 Active TB 142 TST TST No Rx 246 No TST TB (6.5%) No TB 10 TB (0.26%) 4168 TST 30 TB LTBI Rx 144

31 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 Role of Isoniazid Preventative Therapy Akolo, Cochrane Review, 2010

32 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:

33 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 Jones IJATLD Girardi AIDS :13, 1985

34 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 Golub AIDS

35 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 Martinson et al 2011, NEJM 365:11-20

36 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.

37 NICE guidelines for screening

38 Sub-Saharan Africa Medium TB incidence country Low TB incidence country Blood IGRA+++ Blood CD4 count Any<500<350 Duration of ART use <24 months <6 months BHIVA guidelines for screening

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

40 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 , maybe later if TBM Screening recommended but not rolled out

41 Questions?

42 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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