TB and HIV Treatment and Screening

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TB and HIVTreatment and Screening
Santino Capocci
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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

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• 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

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WHO, 2011
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Study Country Active TB prev Rate subclinical of infn Propn with symptoms
Lawn 2010-11 SA 17.3 18 75
Oni 2008-10 SA 8.5 56
Mtei 2001-3 Tanz 15 29-50 37
Shah 2005-6 Ethiopia 7 16 -
Swaminathan India - 4 total -
Corbett 2001 Zimb 1.5 41 -
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SAPIT - Oct 2011

• KwaZulu-Natal (CAPRISA), open label RCT
• 642 patients with TB, CD4 lt500
• 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 lt50
• IRIS 20.1 vs 7.7/100PY

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STRIDE / ACTG A5221 Oct 2011

• Open label, randomised, CD4 lt250
• 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
  CD4lt50
• IRIS 11 vs 5

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CAMELIA - Oct 2011

• CAMbodian Early versus Late Introduction of
  Antivirals
• 2 wk or 8 wk ART into TB treatment CD4 lt200
• 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 lt50 or 50-200
• IRIS rate 3.76 early vs 1.53 / 100PY late (HR
  2.5, Plt0.001)

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BHIVA Guidance
CD4 (cells/µL) When to start HAART
lt100 As soon as practical
100-350 As soon as practical, but can wait until after 2 monthsTB treatment
gt350 Physicians discretion
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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 2011521374
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• 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

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Sterling - After ART

• Review of NA-Accord data from 16 centres
• Risk of TB after starting ART - compared those at
  lt3 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
  wereBlack, Hispanic, IDU, ART naive, CD4 lt200,
  high HIV VL.

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• 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.

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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

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CD4 Italy Italy SA SA
CD4 TST TST- No ART ART
CD4 Incidence (100 PY) Incidence (100 PY) Incidence (100 PY) Incidence (100 PY)
lt200 13.3 1.31 17.5 3.4
200-350 6.54 0.27 12 1.7
350 2.56 0.36 3.6 2.0
Antonucci JAMA1995274143 Badri Lancet
20023592059
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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

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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 20023592059 Girardi. CID
2005411772 Seyler. AJCCRM 2005172123
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NICE guidelines for screening
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BHIVA approach to LTBI

• Balance risk of active TB developing
• vs
• Risk of drug induced hepatotoxicity

Serious hepatotox estimated as 0.3
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BHIVA guidelines for screening
Sub-Saharan Africa Medium TB incidence country Low TB incidence country
Blood IGRA
Blood CD4 count Any lt500 lt350
Duration of ART use lt24 months lt24 months lt6 months
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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
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CD4 Relative risk increase
lt50 10.65
50-199 3.4
200-349 1.77
350-499 1.84
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Origin Incidence (/100PY) Incidence if CD4 lt50 Incidence if CD4 gt500
sSA 0.845 5.11 0.45
MI 0.375 1.19 0.05
LI 0.189 1.06 0.03
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Origin Incidence (/100PY) Incidence if CD4 lt50 Incidence if CD4 gt500
sSA 0.845 5.11 0.45
MI 0.375 1.19 0.05
LI 0.189 1.06 0.03
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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 4494-102
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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
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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
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After having TBany role for IPT again?

• South African gold miners
• Secondary IPT prevented 55 further cases
• NNT 5 and 19 if CD4 lt200 or 200
• No ART

Churchyard, AIDS 2003, 172063-2070
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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 1413, 1985
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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 89CD4lt100 10.7/ 100PY
  TB

Golub AIDS 2007 21 1441Golub AIDS 2009 23 631
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Martinson et al 2011, NEJM 36511-20

• 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

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• Median CD4 484
• Rates of TB
• 3.1 Rpentine/Iso
• 2.9 Ricine/Iso
• 2.7 Isoniazid cont
• 3.6 Isoniazid 6 months
• None inferior to 6 months isoniazid.

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NICE guidelines for screening
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BHIVA guidelines for screening
Sub-Saharan Africa Medium TB incidence country Low TB incidence country
Blood IGRA
Blood CD4 count Any lt500 lt350
Duration of ART use lt24 months lt24 months lt6 months
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• 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

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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 lt100,
  within 8 weeks if 100-350, maybe later if TBM
• Screening recommended but not rolled out

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Questions?
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• 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