TB and HIVTuberculosis Workshop

Shanghai, 12-22 May 2008

Philippe GlaziouWorld Health Organization

Outline

• Epidemiology• Interventions• Response• Challenges and

Opportunities

TB notifications mirror increases inHIV prevalence

Lancet Inf Dis 2006; 6: 483-95 Nature 2005; 5: 819-26

Zimbabwe Kisumu, Kenya

0

50

100

150

200

250

300

350

400

1990

1992

1994

1996

1998

2000

2002

2004

2006

Cas

es p

er 1

00,0

00 p

opul

atio

n

Africa

South-East Asia

WORLD

Western Pacific

EasternMediterraneanEurope

Americas

TB incidence rates driven byHIV in Africa

The TB-HIV link• 5-15% /yr reactivation of TB infection1

• > 11 million at risk of developing TB (1/3 of33.2 million HIV-infected prevalent cases2)

• 9% new TB attributable to HIV in 22 HBCs3

• 224,000 deaths in 20064

• 6-39% case fatality in Africa5, 26-50% inSouth East Asia6

1. Nunn P et al. Nature 2005; 5: 819-26; 2. AIDS Epidemic Update 2007.UNAIDS/07.27E/JC1322E; 3. WHO. TSRU meeting 2007; 4. Floyd K. UnionConference, Cape Town 2007 5. AIDS 2001; 15(2): 143-152; 6. J AcquirImmune Defic Syndr 2006; 43(1)

Global TB-HIV Burden 2006• 2.5 million new HIV infections

• 9.2 million new TB cases– 706,000 TB cases in people living with HIV

• On average 37% of adult TB patients have HIV in

sub-Saharan Africa-nearly 80% in some East and Southern African countries

• Estimated 11% of AIDS deaths due to TBglobally, one third in worst affected countries

TB in people living with HIV• Higher chance for smear negative disease

– Smear negative pulmonary = 24 – 61%– Extrapulmonary = 4 – 40%

• Autopsy studies show undiagnosed TBcaused death in 14 – 54%

• Huge delay in diagnosis (even under idealconditions ranges between 11-34 days)

Opportunistic Illnesses

Indirect estimation of HIVprevalence among incident TB

)1(1 !+

"=

IRRp

IRRpI

HIV

HIVTBHIV

pHIV = prevalence of HIV in adult population

IRR = (TB incidence in HIV+) / (TB incidence in HIV-)

Problem: how to estimate IRR (Incidence Rate Ratio)?

IRR = 30 [21-39] for established market economies

IRR = 6 [3.5 – 8] for all other countries

Source: Corbett et al. Arch Int Med 2003; 163: 1009-1021

Estimated HIV prevalence in new TB cases,2006

No estimate

0–4

20–49

50 or more

5–19

HIV prevalence inTB cases, (%)

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World HealthOrganization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.© WHO 2006. All rights reserved

0 2 0 0 4 0 0 6 0 0 8 0 0 1 0 0 0 1 2 0 0 1 4 0 0

Rwanda

Congo

Côte d'Ivoire

Mozambique

Cambodia

Sierra Leone

Botswana

Zambia

Timor-Leste

Zimbabwe

Lesotho

Namibia

Djibouti

South Africa

Swaziland

All TB

TB with HIV infection

Fifteen countries with the highest estimated TB incidencerates per capita and corresponding incidence rates of HIV-

positive TB cases, 2006

Ethiopia

3%

Kenya

10%

Malawi

5%

Mozambique

4%Nigeria

6%

South Africa

29%

Zambia

3%

Zimbabwe

4%

AFR*

10%

DR Congo

3%

Côte d'Ivoire

2%

UR Tanzania

3%

Swaziland

1%

Uganda

2%

Others

15%

Brazil

AMR*

Russian

Federatn

EUR*

India

SEAR*

WPR

EMR

0

5

10

15

20

Geographical distribution of

HIV-positive TB cases, 2006

For each country or region, the number of incident TBcases arising in people with HIV is shown as a percentageof the global total of such cases. AFR* is all countries inthe WHO African Region except those shown separately;AMR* excludes Brazil; EUR* excludes the RussianFederation; SEAR* excludes India.

Trends in estimated TB incidence rates (all forms, purple lines), and theannual change in incidence rates (red lines), in Africa, 1990–2006

Africa - low HIV

0

50

100

150

200

250

1990 1995 2000 2005

Inc

ide

nc

e r

ate

(p

er

10

0 0

00

/ye

ar)

-10

-5

0

5

10

15

20

25

Ch

an

ge

in

in

cid

en

ce

ra

te (

% p

er

ye

ar)

Africa - high HIV

0

100

200

300

400

500

1990 1995 2000 2005

Inc

ide

nc

e r

ate

(p

er

10

0 0

00

/ye

ar)

-5

0

5

10

15

20

Ch

an

ge in

in

cid

en

ce r

ate

(%

per

ye

ar)

-10

-5

0

5

10

15

20

25

30

1991 1993 1995 1997 1999 2001 2003 2005

% annual change in estimated HIV prevalence

% annual change in TB notification rate

Annual changes (%) in estimated HIV prevalence rate in thegeneral population and the TB case notification rate for sub-

region Africa high-HIV, 1990–2006

Changes are always relative to the preceding year. Estimates of HIV prevalence are from UNAIDS (personal communication)

Correlates of the average annual change inTB incidence rate (vertical axes, %/yr),

1997–2006, in Latin America

r2 = 0.66

-12

-8

-4

0

4

8

12

10 100 1000 10000

Health expenditure per capita ($PPP)

(c) Central and Eastern

Europe

(b) High-income countries

r2 = 0.44

-12

-8

-4

0

4

0 20 40 60 80

Percent of TB cases foreign born

(d) Eastern Mediterranean

r 2 = 0.53

-12

-8

-4

0

4

2 4 6 8 10 12

Health expenditure as percentage of GDP

(a) Latin America

R2 = 0.4105

-10-8-6-4-202468

10

0 1 2 3

Percent adults infected with HIV

(f) Central and Eastern Europe

r2 = 0.67

-12

-8

-4

0

4

8

12

0 10 20 30

Percent of women that smoke

(e) Sub-Saharan Africa

r2 = 0.49

-4

0

4

8

12

10 100 1000

TB expenditure per capita ($PPP)

Treatment outcomes for HIV-positive and HIV-negative TB patients, 2005 cohort

The numbers under the bars are the numbers of patients included in the cohort

0

20

40

60

80

100

HIV+ (6113) HIV- (148570) HIV+ (8100) HIV- (132984) HIV+ (2577) HIV- (34863)

Not evaluated

Transferred

Defaulted

Failed

Died

Completed

Cured

Smear-positive

(data from 47 countries)Smear-negative and extrapulmonary

(data from 42 countries)

Re-treatment

(data from 25 countries)

Decline in HIV incidence, butprevalence stable

AIDS Epidemic Update 2007. UNAIDS/07.27E/JC1322E

Outline

• Epidemiology• Interventions• Response• Challenges and Opportunities

Churchyard et al. JID 2007; (Suppl1) S52: 196

Interventions:

IPT preventsTB disease butnot TBmortality

CPT reduces mortality by up to 48% in AfricaLancet 1999; 353: 1469Cochrane Database Syst Rev 2003; 3: CD003108

Low risk of TBDrug

ResistanceAfter IPT

Balcells et al., EID 2006

HAART prevents TB-HIV mortality inThailand

Acquire Immune Defic Syndr 2006; 43: 1-5

50% case fatality

HAART prevents TB disease in Brazil,but TB incidence remains high

Miranda et al. PLOS 2007; 9, e826

n=306

n=81

n=76

Inc = 1.2 / 100 person-years

Inc = 13.4 / 100 p-y

Inc = 4.9 / 100 p-y

PreventionOptimal timing of ART initiation in those on TB

treatment?

EARLY DELAYED

IRIS and otherconcerns

Risk ofdiseaseprogressionand death

Outline

• Epidemiology• Interventions• Response• Challenges and

Opportunities

Collaborative TB/HIV activities

Interim Policy on Collaborative TB/HIV Activities. WHO Geneva 2004.

National level

Intermediate level

Districtlevel

Primary Care Services level

Community level

Managerial functions of NTP• Planning• Resource allocation• Implementation• Monitoring• Supervision• Training

Service Delivery Functions NTP• Detecting suspects• Diagnosing cases• Treating cases

NTP

National level

Intermediate level

Districtlevel

NAP

Service Delivery Functions NAP• Counselling & testing• Detecting sick people• Treating them• Promotion & prevention

Managerial functions of NAP• Planning• Resource allocation• Implementation• Monitoring• Supervision• Training

National level

Intermediate level

Districtlevel

Primary Care Services level

Community level

NTP

National level

Intermediate level

Districtlevel

NAP

Col

labo

rativ

e In

terv

entio

ns A. Establish mechanism forCollaboration (NTP+NAP)

A.1. TB/HIV coordinating bodies

A.2. HIV surveillance among TB

A.3. Joint TB/HIV planning

A.4. Monitoring and evaluation

B. Decrease burden of TB inPLWHA (primarily NAP)B.1. Intensified TB case findingB.2. IPTB.3. TB infection control

C. Decrease burden of HIVin TB pts (primarily NTP)C.1. HIV testingC.2. HIV preventive methodsC.3. CPTC.4. HIV/AIDS care and supportC.5. Antiretroviral therapy

Collaborative TB/HIV activities

Integrated TB and HIV services throughcollaboration and coordination of NTP and NAP

Mechanisms for collaboration and policies for collaborativeTB/HIV activities, 63 priority countries, 2005–2006

0

10

20

30

40

50

60

Coord inating

body (56%)

Jo in t NTP

and NAP p lan

(91%)

HIV

surveillance

among TB

patien ts

(54%)

HIV

counselling

and testing

o f TB

patien ts

(94%)

CPT fo r HIV-

positive TB

patien ts

(94%)

ART fo r HIV-

positive TB

patien ts

(94%)

In tensified

TB case

find ing

among HIV-

positive

peop le (89%)

Ison iazid

preven tive

therapy (66%)

In fection

contro l (41%)

2005

2006

35

42

34

43

28

43

38

49

38

49

42

52

24

44

2426

20

31

0

100

200

300

400

500

600

700

800

2002(9, 37%) 2003(92, 53%) 2004(84, 61%) 2005(118, 83%) 2006(112, 90%)

Th

ou

san

ds

HIV testing for TB patients, 2002-2006

2

4

6

8

10

12

14

0.5%

4%3.2%

8.5%

12%Figures on top of bars indicatethe percentage of all notified TBpatients tested for HIV

(Number of Countries reporting; % of total estimated HIV+ TB patients accounted for by those Countries)

HIV testing for TB patientsin selected countries, 2006

0 10 20 30 40 50 60 70 80

DR Congo

Ethiopia

India

Cambodia

Nigeria

UR Tanzania

Viet Nam

Zambia

Mozambique

Uganda

South Africa

Botswana

Kenya

Malawi

Brazil

Rwanda

Percentage of all notified TB cases tested

0

10

20

30

40

50

60

70

2003 (47 ,15%) 2004 (25 ,32%) 2005 (47 ,67%) 2006 (54 ,75%)

Th

ou

san

ds

70% 52%

35%

41%

Figures on top of bars indicate theproportion of all HIV positive TBpatients who received ART

(Number of Countries reporting; % of total estimated HIV+ TB patients accounted for by those Countries)

Antiretroviral therapy for HIV-positiveTB patients, 2003–2006

Countries with policy to provide IPT to PLHIV,2006 (N=82)

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or areaor of its authorities, or concerning the delimitation of its frontiers or boundaries.

Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.© WHO 2006. All rights reserved

No policy on IPT

policy on IPT

Key

Djibouti, India, Indonesia, Lesotho, Rwanda and Zambia excludeIPT as a national policy

Countries reported provision of IPT to PLHIV,2006 (N=24)

No reported IPT

Countries reported IPT

Key

* Brazil provide IPT but did not report for 2006

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or ofits authorities, or concerning the delimitation of its frontiers or boundaries.

Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.© WHO 2006. All rights reserved

• Only 0.08% of PLHIV put on IPT globally

• Botswana report 70% of the global PLHIV on IPTNo reported activity

Countries reporting IPT

Key

0

50

100

150

200

250

300

350

Screened for TB

(44, 52%)

Diagnosed with

TB (58, 58%)

Started on IPT

(25, 38%)

0.96%

12%

0.08%

Number of people receiving theintervention as % of estimatedPLHIV in reporting Countries

(Number of Countries reporting; % of total estimated HIV+ TB patients accounted for by those Countries)

Intensified TB case finding, diagnosis of TBand IPT provision among PLHIV, 2006

Proportion of PLHIV screened and diagnosedwith TB in selected countries, 2006

0

20,000

40,000

60,000

80,000

100,000

120,000

South Africa India Ethiopia Rwanda

PLHIV screened for TB

PLHIV with TB after screening

29%

20% 31% 72%

Global progress in implementationof TB-HIV interventions (2002-2006)

99 5 1 4 4 4

92

5627 47 3 3 5

84

7226

25

7

3 3

118

104

4147

13

17 10

111

102

46

54

44

57

24

0

100

200

300

400

500

600

700

800

Tested for

HIV

HIV-positive CPT ART Screened

for TB

Diagnosed

with TB

IPT

Th

ou

san

ds

of

pa

tien

ts

2002

2003

2004

2005

2006

Diagnosis and treatment of HIV in TB patients Dx, Rx and prevention of TB in PLHIV

TOTAL

Figures on top ofbars indicate then u m b e r o fc o u n t r i e sr epo r t i n g t h ea c t i v i t y

Outline

• Epidemiology• Interventions• Response• Challenges and Opportunities

Challenges• Unsatisfactory performance of TB diagnostics• Slow rate of implementation of:

– HIV testing in TB– TB Screening in HIV– IPT

• Infection control often nonexistent• Health system weaknesses:

– Weak M&E systems– Insufficient HR planning and development– Weak commodity-procurement and distribution systems– Weak laboratory networks

Opportunities• Unprecedented funding, e.g. GF, PEPFAR• Momentum gained through the 3 by 5 initiative• Provider-initiated HIV testing and counseling

policy• Lessons from:

– Successful pilots of integrated TB and HIV care (e.g.Khayelistha, SA; START study, Durban, SA; Cambodia)

– National IPT programmes (Botswana)• Accelerated R&D in TB diagnostics• Advocacy impact of XDR-TB-HIV outbreak with

98% case fatality in Tugela Ferry, SA

Conclusions

• Encouraging, yet insufficient, progress inscaling-up collaborative TB/HIV activities

• Some progress in providing HIV care to TBpatients (testing, CTX, ART)

• IPT, intensified case finding, and TB careshould be core functions of HIV services

• Infection control is lacking in most settingsand must become a top priority for all

“We can’t fight AIDS unless we domuch more to fight TB as well."

Nelson MandelaBangkok, 15 July 2004

Source: From the CREATE projectNelson Mandela, Former President of South Africa and Nobel peace prize winner 1993