Isoniazid preventive therapy for people living with HIV:

1. Isoniazid preventive therapy for people living with HIV: Public health challenges and implementation issues Peter Godfrey-Faussett UNAIDS (with thanks to Lisa Nelson and Haileyesus Getahun) IAS2013, Kuala Lumpur 2 July 2013

2. Preventive Therapy for Tuberculosis “Treatment of infection has been a possibility only since the introduction of isoniazid. …... its efficacy is established. It can be expected that efficacy will increase with new regimens and new drugs. Surely, the most important task ahead is social research to determine the efficient and economical ways to bring treatment to those who benefit.”

3. Preventive Therapy for Tuberculosis “Treatment of infection has been a possibility only since the introduction of isoniazid. …... its efficacy is established. It can be expected that efficacy will increase with new regimens and new drugs. Surely, the most important task ahead is social research to determine the efficient and economical ways to bring treatment to those who benefit.” Ferebee, SH. Adv Tub Res 1969;17:28-106

4. TB is a leading cause of death among PLHIV References 1. AIDS 2001; 15(2): 143-152; 2. J Acquir Immune DeficSyndr 2006; 43(1);’3. Emerg Inf Dis 2007; 13(7): 1001-7; 4. Int J Tuberc Lung Dis 2007; 11(9): 1008-1013; 5. Int J Tuberc Lung Dis 2006; 10: 45–51; 6. Int J Tuber Lung Dis 2006; 10(1): 45-51 • References • Lucas et al , 1994; 2. Afessa et al, 1998; 3. Ranna et al, 2000; 4. Ansari et al, 2002; 5. Martinson et al, 2007; 6. Lanjewar, 2011; 7. Cox et al, 2012 430,000 PLHIV died of TB in 2011 (25% of AIDS deaths)

5. IPT Reduces the Risk of TB among PLHIV 1.0 1.0 0.36 0.74 0.86 1.02 0.86 0.81 0.67 0.95 Akolo. 2010, Cochrane review

6. Lancet 2011

8. IPT with ART: A Randomised Controlled Trial • HR:0.63 (95% CI 0.41-0.94) • Deaths were similar between arms (3.0% vs. 2.1%, p=0.29) • The risk of stopping IPT due to grade 3 or more raised ALT was 2.13 (95%CI 0.97-4.67) Cumulative TB incidence (Rangaka et al, AIDS2012)

9. The 12 points policy package: What's new? A. Establish the mechanisms for integrated TB & HIV services 1. Set up or strengthen a TB/HIV coordinating body effective at all levels 2. Conduct HIV and TB surveillance among TB and HIV patients respectively 3. Carry out joint TB/HIV planning 4. Conduct monitoring and evaluation B. Decrease the burden of TB in PLHIV (Three Is for HIV/TB) 5. Intensify TB case finding and ensure quality TB treatment 6. Introduce TB prevention with IPT and ART 7. Infection control for TB in health care and congregate settings Joint HIV and TB HIV programme C. Decrease the burden of HIV in patients with presumptive anddiagnosed TB 8. Provide HIV testing & counselling to patients with presumptive and diagnosed TB 9. Introduce HIV preventive methods patients with presumptive and diagnosed TB 10. Provide CPT for TB patients living with HIV 11. Ensure HIV prevention, treatment & care for TB patients living with HIV 12. Provide Antiretroviral therapy to TB patients living with HIV TB programme

10. GRC approved WHO guidelines on Three Is for HIV/TB 2012 2009 2010

11. Global TB screening among people living with HIV (n) 3.2 million 195,000 Global Isoniazid TB preventive treatment for PLHIV (n) 450,000 IPT was given to 1800 PLHIV in WPR in 2011 (72% from Cambodia) 26,000

12. Why do we not implement an intervention with such a strong evidence base and such strong recommendations?

13. TB and HIV programme isolation • Isoniazid is for treatment not prevention • Fears of drug resistance • Difficulties screening out active TB • Logistics of TST tests for patients and providers • Juice not worth the squeeze? • Integrate care, coordinate management • CfPrEP, new regimens coming for treatment and for prevention • Largely unjustified • Need high NPV • Consider opt-out? • How many people with HIV do you want to treat to prevent a case of TB?