1. TB-HIV INTEGRATION IN THE WORKPLACE 2 nd Private Sector Conference on HIV and AIDS Presenter: Dr S Charalambous

2. Presentation outline TB burden in HIV-infected individuals WHO TB-HIV collaborative activities 3 Is strategy: –Intensive case finding –INH preventive therapy –Infection control ART and TB Current TB projects

6. HIV and TB Co-infection If already TB-infected: HIV increases the risk of developing active TB -10%/lifetime - 10%/yr If newly TB-infected: more likely to progress to active disease Taking ART and TB treatment together can be problematic : Side effects, compliance, IRIS TB presents differently in HIV-infected persons – making diagnosis more difficult TB is now the leading cause of death among HIV infected persons

7. WHO 2004 - Key elements of TB-HIV integration Establish mechanisms for collaboration : –Set up a co-ordinating body for TB/HIV activities effective at all levels –Conduct surveillance of HIV prevalence among tuberculosis patients –Carry out joint TB/HIV planning –Conduct monitoring and evaluation Decrease the burden of TB in people living with HIV/AIDS –Establish intensified tuberculosis case finding –Introduce isoniazid preventive therapy –Ensure tuberculosis infection control in health care and congregate settings Decrease the burden of HIV in TB patients : –Provide HIV testing and counselling –Introduce HIV prevention methods –Introduce cotrimoxazole preventive therapy –Ensure HIV/AIDS care and support –Introduce antiretroviral therapy

8. Key elements of TB-HIV integration Establish mechanisms for collaboration : –Set up a co-ordinating body for TB/HIV activities effective at all levels –Conduct surveillance of HIV prevalence among tuberculosis patients –Carry out joint TB/HIV planning –Conduct monitoring and evaluation Decrease the burden of TB in people living with HIV/AIDS –Establish intensified tuberculosis case finding –Introduce isoniazid preventive therapy –Ensure tuberculosis infection control in health care and congregate settings Decrease the burden of HIV in TB patients : –Provide HIV testing and counselling –Introduce HIV prevention methods –Introduce cotrimoxazole preventive therapy –Ensure HIV/AIDS care and support –Introduce antiretroviral therapy

9. Intensive case finding Community-based ART programme in Cape Town* –active screening for TB prior to ART (2002-2005) –477/923 (52%) previous TB at enrolment –238/923 (25%) active TB at enrolment (>50% already on TB Rx) Home-based ART programme in Uganda** –Active screening for TB prior to ART (2003-2005) –75/1044 (7.2%) active TB at baseline (50% already on TB Rx) * Lawn AIDS 2006 **Moore AIDS 2007

10. SA National ART guidelines 2004 Prior to initiating ART –Suspect TB if 2 or more of: Observed weight loss ≥ 1.5 kg Cough > 2 weeks Night sweats > 2 weeks Fever > 2 weeks –2 sputum specimens (2 AFB, 1 culture) Prior to IPT –As above, but investigate if 1 or more symptom –2 sputum AFB, 1 sputum culture

11. Screening for TB prior to ART initiation in community and industrial programme settings in South Africa Objectives: – Describe current practice in screening for TB among patients attending industrial and community HIV care programmes prior to ART initiation –Assess adherence to national guidelines on investigation and screening for TB suspects Yasmeen Hanifa

12. Results: symptom screen and sputum investigation † any of: cough / sputum production/ fever / night sweats / weight loss; ‡ two or more of: cough / fever / night sweats / weight loss Community N=4502 n (%) Industrial N=1883 n (%) Any symptom ticked†2573 (57.2)579 (30.8) Two or more symptoms ticked‡1524 (33.9)307 (16.3) Sputum sent52 (1.2)95 (5.1) Screening according to SA national guidelines (Patients with two or more symptoms who had sputum sent) ‡ 27/1524 (1.8)44/307 (14.3) Patients with CXR suggestive of TB who had sputum sent7/258 (2.7)18/130 (13.9)

13. Conclusions Screening for TB / adherence to national guidelines, or its documentation, or both, were poor Offer investigations on site, free of charge Clinical data systems should facilitate care by prompting care providers to screen for TB

14. Isoniazid Preventive therapy Recommended by WHO since 2005 –All HIV infected persons with no previous history of TB regardless of CD4 count for period of 6 months –Persons with silicosis Given as a once-daily dose Need to exclude TB prior to use

15. Efficacy of primary isoniazid TB preventive therapy (IPT ) PPD+TB incidenceDeath Author / yearRelative Risk 95% CI Hawken 19970.64 [0.22, 1.87]0.34 [0.10, 1.21] Mwinga 19980.42 [0.14, 1.24]2.02 [0.63, 6.51] Pape 19930.22 [0.05, 1.00]0.28 [0.08, 0.99] Whalen 19970.29 [0.12, 0.67]0.78 [0.56, 1.09] Sub Total0.36 [0.22, 0.61]0.74 [0.55, 1.00]

16. Systematic review of published data since 1951 13 studies, On IPT = 18095, controls = 17,985 Summary RR of resistance 1.45 (95% CI 0.85 – 2.47) Results similar when stratified by HIV Findings do not exclude an increased risk of isoniazid- resistant TB after IPT Surveillance for isoniazid resistance is required IPT & drug resistance (Balcells ME, Emerging Infectious Diseases, 2006)

23. WHO 1&2 ART & TB incidence (Badri, Lancet. 2002)

25. Antiretroviral therapy and TB incidence in South African Platinum miners Mean estimate & 95% CI

26. Kaplan Meier graph of TB incidence on patients started on ART by CD4 count at start of ART

27. Results: Univariate and Multivariate analysis of baseline characteristics associated with TB incidence in patients who are on ART P T = linear test for trend Univariate analysisMultivariate analysis (baseline variables) Incidence Rate Ratio (IRR) 95% CIIncidence Rate Ratio (IRR) 95% CI Age group (in years) <30 30-39 40-49 ≥ 50 1.00 1.76 1.80 2.28 P T =0.05 0.75 – 4.13 0.79 – 4.11 0.98 – 5.29 1.00 1.46 1.26 1.62 P T =0.34 0.62 – 3.44 0.55 – 2.89 0.69 – 3.79 Previous TBNo Yes 1.00 1.64 P<0.001 1.25 – 2.17 1.00 1.50 P=0.01 1.09 – 2.07 CD4 count group at baseline ≤ 50 51-250 251-350 >350 1.00 1.25 0.78 0.55 P T =0.02 0.80 – 1.94 0.48 – 1.27 0.23 – 1.35 1.00 1.20 0.94 0.45 P T =0.10 0.75 – 1.91 0.56 – 1.55 0.15 – 1.31 Viral load group at baseline <10 000 10000-100000 >100 000 1.00 1.49 1.92 P T <0.01 0.92 – 2.41 1.17 – 3.14 WHO stage at baseline 12341234 1.00 1.09 2.11 1.72 P<0.01 0.57 – 2.08 1.25 – 3.55 0.94 – 3.16 1.00 1.02 1.66 1.40 P=0.10 0.52 – 1.99 0.96 – 2.85 0.74 – 2.68

28. Results: Univariate and Multivariate analysis of time-dependent factors associated with TB incidence in patients who are on ART P T = linear test for trend Univariate analysisMultivariate analysis (baseline variables) Incidence Rate Ratio (IRR) 95% CIIncidence Rate Ratio (IRR) 95% CI Stopped ART No Yes 1.00 1.82 P<0.001 1.38 – 2.39 1.00 1.86 P<0.001 1.38 – 2.52 Change at 6 weeks <1 log >1 log 1.00 0.53 P<0.01 0.35 – 0.82 Follow-up time <180 d 181 – 360 d 361 – 540 d 540 – 720d 720 - 900 d >900d 1.00 0.81 0.54 0.56 0.28 0.40 P T <0.001 0.57 – 1.14 0.34 – 0.83 0.35 – 0.92 0.13 – 0.61 0.24 – 0.69 1.00 0.78 0.54 0.55 0.30 0.41 P T <0.001 0.53 – 1.13 0.34 – 0.87 0.32 – 0.93 0.14 – 0.66 0.24 – 0.72

30. THRio Cohort: HAART initiation after TB diagnosis improves survival Saraceni V, et al. IAC 2008. Abstract MOAB0305. Retrospective, observational cohort of 662 HAART-naive patients diagnosed with TB in Rio de Janeiro, Brazil 0.8 Days Proportion Surviving 0.9 0 500 1000 1500 0.7 0.8 0.9 1.0 Days Proportion Surviving 1.0 0 500 1000 1500 No HAART HAART By HAART Exposure < 200 cells/mm 3 ≥ 200 cells/mm 3 By CD4+ Count Category P <.001 0.7 P =.985

31. TB PROJECTS Cluster randomised trial in gold miners All miners offered TB Preventive Therapy for 9 months Funded by Bill and Melinda Gates Foundation Over 16000 miners already on INH COLLABORATORS London School of Hygiene and Tropical Medicine Johns Hopkins University AngloGold Ashanti Gold Fields Harmony Gold Department of Minerals and Energy Department of Health Department of Labour Mining Unions and Associations

32. Conclusions Back to basics! –TB case finding, INH Prevention, Infection control ARV reduces TB incidence in HIV patients but still very high Lets not forget the health workers - efforts to protect them need to be implemented.

34. Aurum Institute for Health Research Prof. G J Churchyard Dr Dave Clark Dr C Morris Dr C Innes Dr M Shisana Dr L Pemba Mr T Puso Mr S Senoge Mr M Eisenstein Presentations used Shaheen Mehtar Steve Lawn Kevin De Cock London School of Hygiene and Tropical Medicine Dr K Fielding Dr A Grant Funders Anglo Coal Anglo Platinum PEPFAR Anglo American Acknowledgments