TB-HIV INTEGRATION IN THE WORKPLACE

2nd Private Sector Conference on HIV and AIDSPresenter: Dr S Charalambous

Presentation outline

TB burden in HIV-infected individualsWHO TB-HIV collaborative activities3 Is strategy:– Intensive case finding– INH preventive therapy– Infection control

ART and TBCurrent TB projects

HIV and TB Co-infection

If already TB-infected: HIV increases the risk of developing active TB -10%/lifetime - 10%/yrIf newly TB-infected: more likely to progress to active diseaseTaking ART and TB treatment together can be problematic : Side effects, compliance, IRISTB presents differently in HIV-infected persons – making diagnosis more difficultTB is now the leading cause of death among HIV infected persons

WHO 2004 - Key elements of TB-HIV integrationEstablish 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

Key elements of TB-HIV integrationEstablish 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

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

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

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

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

CommunityN=4502n (%)

IndustrialN=1883n (%)

Any symptom ticked† 2573 (57.2) 579 (30.8)

Two or more symptoms ticked‡ 1524 (33.9) 307 (16.3)

Sputum sent 52 (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 sent 7/258 (2.7) 18/130 (13.9)

Conclusions

Screening for TB / adherence to national guidelines, or its documentation, or both, were poorOffer investigations on site, free of chargeClinical data systems should facilitate care by prompting care providers to screen for TB

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 doseNeed to exclude TB prior to use

Efficacy of primary isoniazid TB preventive therapy (IPT)

PPD+ TB incidence Death

Author / year Relative Risk Relative Risk

95% CI 95% CI

Hawken 1997 0.64 [0.22, 1.87] 0.34 [0.10, 1.21]

Mwinga 1998 0.42 [0.14, 1.24] 2.02 [0.63, 6.51]

Pape 1993 0.22 [0.05, 1.00] 0.28 [0.08, 0.99]

Whalen 1997 0.29 [0.12, 0.67] 0.78 [0.56, 1.09]

Sub Total 0.36 [0.22, 0.61] 0.74 [0.55, 1.00]

Systematic review of published data since 195113 studies, On IPT = 18095, controls = 17,985Summary RR of resistance

• 1.45 (95% CI 0.85 – 2.47)

Results similar when stratified by HIVFindings 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)

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30

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WHO 1&2

ART & TB incidence

(Badri, Lancet. 2002)

Antiretroviral therapy and TB incidence in South African Platinum miners

Mean estimate & 95% CI

TB incidence (first episode) following ART initiation

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<45days 45-90days 91-180days 181-365days 365-545days 546-720days

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

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0 .5 1 1.5 2 2.5 3 3.5 4 4.5 5analysis time in years

<=50 51-250

251-350 >350

Results: Univariate and Multivariate analysis of baseline characteristics associated with TB incidence in patients who are on ART

PT = linear test for trend

Univariate analysis Multivariate analysis(baseline variables)

Incidence Rate Ratio (IRR)

95% CI Incidence Rate Ratio (IRR)

95% CI

Age group (in years)

<3030-3940-49≥ 50

1.001.761.802.28

PT=0.050.75 – 4.130.79 – 4.110.98 – 5.29

1.001.461.261.62

PT=0.340.62 – 3.440.55 – 2.890.69 – 3.79

Previous TB

NoYes

1.001.64

P<0.0011.25 – 2.17

1.001.50

P=0.011.09 – 2.07

CD4 count group at baseline

≤ 5051-250251-350>350

1.001.250.780.55

PT=0.020.80 – 1.940.48 – 1.270.23 – 1.35

1.001.200.940.45

PT=0.100.75 – 1.910.56 – 1.550.15 – 1.31

Viral load group at baseline

<10 00010000-100000>100 000

1.001.491.92

PT<0.010.92 – 2.411.17 – 3.14

WHO stage at baseline

1234

1.001.092.111.72

P<0.010.57 – 2.081.25 – 3.550.94 – 3.16

1.001.021.661.40

P=0.100.52 – 1.990.96 – 2.850.74 – 2.68

Results: Univariate and Multivariate analysis of time-dependent factors associated with TB incidence in patients who are on ART

PT = linear test for trend

Univariate analysis Multivariate analysis(baseline variables)

Incidence Rate Ratio (IRR)

95% CI Incidence Rate Ratio (IRR)

95% CI

Stopped ART

NoYes

1.001.82

P<0.0011.38 – 2.39

1.001.86

P<0.0011.38 – 2.52

Change at 6 weeks

<1 log>1 log

1.000.53

P<0.010.35 – 0.82

Follow-up time

<180 d181 – 360 d361 – 540 d540 – 720d720 - 900 d>900d

1.000.810.540.560.280.40

PT<0.0010.57 – 1.140.34 – 0.830.35 – 0.920.13 – 0.610.24 – 0.69

1.000.780.540.550.300.41

PT<0.0010.53 – 1.130.34 – 0.870.32 – 0.930.14 – 0.660.24 – 0.72

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

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No HAARTHAART

By HAART Exposure

< 200 cells/mm3

≥ 200 cells/mm3

By CD4+ Count Category

P < .001

0.7

P = .985

TB PROJECTS

Cluster randomised trial in gold minersAll miners offered TB Preventive Therapy for 9 monthsFunded by Bill and Melinda Gates FoundationOver 16000 miners already on INH

COLLABORATORSLondon 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

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.

Aurum Institute for Health ResearchProf. G J ChurchyardDr Dave ClarkDr C MorrisDr C Innes Dr M Shisana Dr L PembaMr T PusoMr S SenogeMr M Eisenstein

Presentations used Shaheen MehtarSteve LawnKevin De Cock

London School of Hygiene and Tropical MedicineDr K FieldingDr A Grant

FundersAnglo CoalAnglo PlatinumPEPFARAnglo American

Acknowledgments