TB-HIV Update Asilomar 2007 Jacqueline Tulsky, MD SF AETC and SFGH Positive Health Program Francis J. Curry National TB Center Lisa Chen, MD Francis J.

TB-HIV UpdateAsilomar 2007

Jacqueline Tulsky, MD

SF AETC and SFGH Positive Health Program

Francis J. Curry National TB Center

Lisa Chen, MD

Francis J. Curry National TB Center

New and Reinforced for 2007New and Reinforced for 2007 Journal of Infectious Diseases Journal of Infectious Diseases

August, 2007 SupplementAugust, 2007 Supplement

MDR, XDR and whose MDR, XDR and whose nonadherent w/TBnonadherent w/TB

Data on IGRAsData on IGRAs

Modeling the partnership of TB Modeling the partnership of TB and HIV programsand HIV programs

The Journal of Infectious Diseases The Journal of Infectious Diseases 15 August 2007; Vol 196, No. S115 August 2007; Vol 196, No. S1

TUBERCULOSIS AND HIV COINFECTIONTUBERCULOSIS AND HIV COINFECTION

Current State of Knowledge and ResearchCurrent State of Knowledge and ResearchPrioritiesPriorities

14 articles on the full range of HIV/TB issues 14 articles on the full range of HIV/TB issues

124 pages and available through the HIV Insite 124 pages and available through the HIV Insite Link and from publisher $10Link and from publisher $10

Treatment Options Treatment Options for HIV Associated TB for HIV Associated TB

Onyebujoh P, Ribeiro I, Whalen COnyebujoh P, Ribeiro I, Whalen CJID Aug 15, 2007JID Aug 15, 2007

A major help to TB-HIV A major help to TB-HIV coinfection treatment is that..coinfection treatment is that..

1.1. Rifabutin went off Rifabutin went off patent in 2000patent in 2000

2. Hepafilters are 2. Hepafilters are being distributed being distributed throughout the throughout the developing worlddeveloping world

3. New HIV drug 3. New HIV drug treatments do not treatments do not interact with first interact with first line TB drugsline TB drugs

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2121 2222 2323 2424 2525 2626 2727 2828 2929 3030

Treatment Options for HIV-TB are Slow Treatment Options for HIV-TB are Slow to Changeto Change

No identified manufacturer for No identified manufacturer for generic rifabutingeneric rifabutin

Treatment Options for HIV-TB are Slow Treatment Options for HIV-TB are Slow To ChangeTo Change

All boosted PIs need rifabutinAll boosted PIs need rifabutin

raltegravir and etravarineraltegravir and etravarine• Interactions = YESInteractions = YES• Guidelines how to use = NOGuidelines how to use = NO

maraviroc 78% decrease in maraviroc 78% decrease in levels w/ rifampinlevels w/ rifampin

New Tuberculosis DrugsNew Tuberculosis Drugs

Patient With History of Previous Patient With History of Previous TreatmentTreatment

60 yr old HIV positive man is seen in 60 yr old HIV positive man is seen in clinic with positive blood test for TB clinic with positive blood test for TB infectioninfection

His evaluation is negative for active TB, His evaluation is negative for active TB, and he is offered INH prevention, which and he is offered INH prevention, which unenthusiastically acceptsunenthusiastically accepts

He tells the clinic nurse that he doesn’t He tells the clinic nurse that he doesn’t want that old drug that his brother was want that old drug that his brother was on years ago, there must be something on years ago, there must be something newer for TB preventionnewer for TB prevention

The last novel compounds for TB The last novel compounds for TB treatment were released…treatment were released…

1. 5 years ago1. 5 years ago

2. 20 years ago2. 20 years ago

3. 40 years ago3. 40 years ago

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2121 2222 2323 2424 2525 2626 2727 2828 2929 3030

Treatment Options in the TB PipelineTreatment Options in the TB Pipeline

7 new compounds are in 7 new compounds are in development specifically for TBdevelopment specifically for TB

Some are familiar old names – Some are familiar old names – moxifloxacin and cousin moxifloxacin and cousin gatifloxacingatifloxacin

Others in early development Others in early development may not make it, but the push may not make it, but the push is onis on

DefinitionsDefinitions

MDR-TBMDR-TB

– Resistance to at least isoniazid and Resistance to at least isoniazid and rifampinrifampin

– ImportanceImportance No short course treatment regimen No short course treatment regimen

available available Requires use of more toxic drugsRequires use of more toxic drugs

Definitions (2)Definitions (2)

XDR-TBXDR-TB

– Resistant to at least isoniazid, Resistant to at least isoniazid, rifampin, rifampin,

plus plus

– resistance to any fluoroquinoloneresistance to any fluoroquinolone

and and

– at least one of three injectable at least one of three injectable second-line drug (amikacin, second-line drug (amikacin, kanamycin, or capreomycin)kanamycin, or capreomycin)

Extensively Drug-resistant Extensively Drug-resistant (XDR) TB in Rural S. Africa(XDR) TB in Rural S. Africa

185 (39%) pts w/ TB had MDR-TB 185 (39%) pts w/ TB had MDR-TB 53 with XDR53 with XDR 44 (53?) tested had HIV44 (53?) tested had HIV 52 of 53 with XDR TB died52 of 53 with XDR TB died Median survival of 16 days from Median survival of 16 days from

diagnosisdiagnosis

Source: Gandhi, et al. Lancet 368:2006.Source: Gandhi, et al. Lancet 368:2006.

XDR-TB in US 1993-2006XDR-TB in US 1993-2006N = 49N = 49

PAETC and NWAETC RegionPAETC and NWAETC Region• CaliforniaCalifornia 1111

• NevadaNevada 2 2

93-9993-99 00-0600-06• HIVHIV 44%44% 12% 12%

• Foreign bornForeign born 38%38% 76%76%

DiedDied 33%33% 12% 12%

!!Lost moved or other!! !!Lost moved or other!! 24%24% CDC MMWR 2007;56:250-253CDC MMWR 2007;56:250-253

The New Face of the The New Face of the Challenging Patient Challenging Patient

““Investigation of U.S. Traveler with Investigation of U.S. Traveler with Extensively Drug Resistant Extensively Drug Resistant Tuberculosis (XDR TB)”Tuberculosis (XDR TB)”

CDC Health Alert Network, May 29, 2007CDC Health Alert Network, May 29, 2007

Adherence ChallengeAdherence Challenge AS is a 32 yo US born Caucasian AS is a 32 yo US born Caucasian

lawyer with an incidental finding of lawyer with an incidental finding of lung lesion on CXR lung lesion on CXR

Known smear negative, culture Known smear negative, culture positivepositive

Nonadherent to “no travel” adviceNonadherent to “no travel” advice Takes long international flights after Takes long international flights after

being told about XDR TBbeing told about XDR TB Comes over border from Canada to Comes over border from Canada to

USUS

Blood Tests for TB screening:Blood Tests for TB screening:

Interferon Interferon releasing assays (IGRAs)releasing assays (IGRAs)

Whole blood (5cc) test

Measures immune reactivity to M. tb

QuantiFERON (QFT) and Elispot both commercially licensed

DO NOT DISTINGUISH LATENT from ACTIVE TB

IGRAs compared to TSTsIGRAs compared to TSTs

In vitroIn vitro Multiple antigensMultiple antigens No boostingNo boosting 1 patient visit1 patient visit Minimal inter-Minimal inter-

reader variability reader variability Results in 1 dayResults in 1 day Stimulate w/ 12 Stimulate w/ 12

hrshrs

In vivoIn vivo Single antigenSingle antigen BoostingBoosting 2 patient visits2 patient visits Inter-reader Inter-reader

variability variability Results in 2-3 daysResults in 2-3 days Read in 48-72 hrsRead in 48-72 hrs

IGRAs for TB ScreeningIGRAs for TB Screening Sensitivity suboptimal Sensitivity suboptimal

• Elispot-6 best at 93%Elispot-6 best at 93%

Pooled specificity better Pooled specificity better • QFT up to 98% QFT up to 98% • Elispot 92%Elispot 92%

Discordance with HIV positive pts Discordance with HIV positive pts between IGRAs and TST between IGRAs and TST • Frequent (6-12%)Frequent (6-12%)• UnexplainedUnexplained

Menzies D, Pai M, Comstock G - Annals Int Menzies D, Pai M, Comstock G - Annals Int Med Med 2007;146:340-3542007;146:340-354

Strategies for TB screeningStrategies for TB screening

Use preferred method TST or IGRAUse preferred method TST or IGRA

• If NEGATIVE and HIGH RISK for TB, If NEGATIVE and HIGH RISK for TB, repeat using other test and accept a repeat using other test and accept a positive by either methodpositive by either method

Wait for QFT-Intube for ease of use if Wait for QFT-Intube for ease of use if transport and lab logistics a major transport and lab logistics a major challengechallenge

Modeling the Partnerships of HIV Modeling the Partnerships of HIV and TB Clinical careand TB Clinical care

““NO MATTER HOW CYNICAL I BECOME….NO MATTER HOW CYNICAL I BECOME….

I JUST CAN’T KEEP UP”I JUST CAN’T KEEP UP”

Lily TomlinLily Tomlin

HIV/TBHIV/TB Collaboration and Integration Collaboration and Integration

The smaller the number of cases, the The smaller the number of cases, the more likely one clinic and one clinical more likely one clinic and one clinical infectious disease specialist and infectious disease specialist and his/her team will manage both TB and his/her team will manage both TB and HIVHIV

Program Collaboration and Integration Program Collaboration and Integration remains a challenge on the global remains a challenge on the global scale with smaller bad examples in scale with smaller bad examples in the USthe US

TB Warmline ConsultationTB Warmline Consultation

F.J. Curry National TB CenterF.J. Curry National TB Center

415-502-4700415-502-4700