1. 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. Curry National TB Center

2. New and Reinforced for 2007 Journal of Infectious Diseases August, 2007 Supplement Journal of Infectious Diseases August, 2007 Supplement MDR, XDR and whose nonadherent w/TB MDR, XDR and whose nonadherent w/TB Data on IGRAs Data on IGRAs Modeling the partnership of TB and HIV programs Modeling the partnership of TB and HIV programs

3. The Journal of Infectious Diseases 15 August 2007; Vol 196, No. S1 TUBERCULOSIS AND HIV COINFECTION Current State of Knowledge and Research Priorities 14 articles on the full range of HIV/TB issues 124 pages and available through the HIV Insite Link and from publisher $10

4. Treatment Options for HIV Associated TB Onyebujoh P, Ribeiro I, Whalen C JID Aug 15, 2007

5. A major help to TB-HIV coinfection treatment is that.. 1.Rifabutin went off patent in 2000 2. Hepafilters are being distributed throughout the developing world 3. New HIV drug treatments do not interact with first line TB drugs

6. Treatment Options for HIV-TB are Slow to Change No identified manufacturer for generic rifabutin

7. Treatment Options for HIV-TB are Slow To Change All boosted PIs need rifabutin All boosted PIs need rifabutin raltegravir and etravarine raltegravir and etravarine Interactions = YES Interactions = YES Guidelines how to use = NO Guidelines how to use = NO maraviroc 78% decrease in levels w/ rifampin maraviroc 78% decrease in levels w/ rifampin

8. New Tuberculosis Drugs

9. Patient With History of Previous Treatment 60 yr old HIV positive man is seen in clinic with positive blood test for TB infection 60 yr old HIV positive man is seen in clinic with positive blood test for TB infection His evaluation is negative for active TB, and he is offered INH prevention, which unenthusiastically accepts His evaluation is negative for active TB, and he is offered INH prevention, which unenthusiastically accepts He tells the clinic nurse that he doesn’t want that old drug that his brother was on years ago, there must be something newer for TB prevention He tells the clinic nurse that he doesn’t want that old drug that his brother was on years ago, there must be something newer for TB prevention

10. The last novel compounds for TB treatment were released… 1. 5 years ago 2. 20 years ago 3. 40 years ago

11. Treatment Options in the TB Pipeline 7 new compounds are in development specifically for TB 7 new compounds are in development specifically for TB Some are familiar old names – moxifloxacin and cousin gatifloxacin Some are familiar old names – moxifloxacin and cousin gatifloxacin Others in early development may not make it, but the push is on Others in early development may not make it, but the push is on

12. Definitions MDR-TB MDR-TB – Resistance to at least isoniazid and rifampin – Importance  No short course treatment regimen available  Requires use of more toxic drugs

13. Definitions (2) XDR-TB XDR-TB – Resistant to at least isoniazid, rifampin, plus – resistance to any fluoroquinolone and and – at least one of three injectable second-line drug (amikacin, kanamycin, or capreomycin)

14. Extensively Drug-resistant (XDR) TB in Rural S. Africa 185 (39%) pts w/ TB had MDR-TB 185 (39%) pts w/ TB had MDR-TB 53 with XDR 53 with XDR 44 (53?) tested had HIV 44 (53?) tested had HIV 52 of 53 with XDR TB died 52 of 53 with XDR TB died Median survival of 16 days from diagnosis Median survival of 16 days from diagnosis Source: Gandhi, et al. Lancet 368:2006.

15. XDR-TB in US 1993-2006 N = 49 PAETC and NWAETC Region California11California11 Nevada 2Nevada 2 93-9900-06 93-9900-06 HIV44% 12%HIV44% 12% Foreign born38% 76%Foreign born38% 76% Died33% 12% !!Lost moved or other!! 24% CDC MMWR 2007;56:250-253 CDC MMWR 2007;56:250-253

16. The New Face of the Challenging Patient “ Investigation of U.S. Traveler with Extensively Drug Resistant Tuberculosis (XDR TB)” CDC Health Alert Network, May 29, 2007

18. Adherence Challenge  AS is a 32 yo US born Caucasian lawyer with an incidental finding of lung lesion on CXR  Known smear negative, culture positive  Nonadherent to “no travel” advice  Takes long international flights after being told about XDR TB  Comes over border from Canada to US

19. Blood Tests for TB screening:  Interferon releasing assays (IGRAs)  Interferon  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

20. IGRAs compared to TSTs  In vitro  Multiple antigens  No boosting  1 patient visit  Minimal inter- reader variability  Results in 1 day  Stimulate w/ 12 hrs  In vivo  Single antigen  Boosting  2 patient visits  Inter-reader variability  Results in 2-3 days  Read in 48-72 hrs

21. IGRAs 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 between IGRAs and TST Discordance with HIV positive pts between IGRAs and TST Frequent (6-12%)Frequent (6-12%) UnexplainedUnexplained Menzies D, Pai M, Comstock G - Annals Int Med 2007;146:340-354

22. Strategies for TB screening Use preferred method TST or IGRA If NEGATIVE and HIGH RISK for TB, repeat using other test and accept a positive by either methodIf NEGATIVE and HIGH RISK for TB, repeat using other test and accept a positive by either method Wait for QFT-Intube for ease of use if transport and lab logistics a major challenge

23. Modeling the Partnerships of HIV and TB Clinical care “NO MATTER HOW CYNICAL I BECOME…. I JUST CAN’T KEEP UP” Lily Tomlin

24. HIV/TB Collaboration and Integration The smaller the number of cases, the more likely one clinic and one clinical infectious disease specialist and his/her team will manage both TB and HIV Program Collaboration and Integration remains a challenge on the global scale with smaller bad examples in the US

25. TB Warmline Consultation F.J. Curry National TB Center F.J. Curry National TB Center415-502-4700