TB and HIV: from clinical practice to public health action

Alberto MatteelliInstitute of Infectious and Tropical Diseases

University of Brescia, ItalyWHO Collaborative Centre on TB/HIV co-infection

Outline of the presentation

• Burden of HIV associated TB• Impact of HAART on the epidemiology of HIV

associated TB• Diagnostic standards and perspectives for HIV

associated TB• How to treat the TB/HIV co-infection (choice of

drugs, timing, managemert of IRIS)• Prevention of TB in HIV infected persons (early

diagnosis, IPT, ART)• WHO recommended TB/HIV activities

How HIV influences the TB natural history

Post-primary TB

Primary TB

M. tuberculosis

First Infection

LatentTB

Re-infection (exogenous)

Reactivation (endogenous)

Progressive Primary TB

HIV positive

Relative risk for TB:

HIV neg. = < 10% per lifetime

HIV pos. ~ 3-7 % per year

Infection

with HIV

Infection

with

M.

tuberculosis

Sub-Saharan African country

TB/HIV Co-infectionOverlap of two populations

Estimated HIV prevalence in new TB cases, 2009

WHO, Global TB report 20101.1 million TB/HIV cases and 400,000 deaths

Estimated TB incidence vs. HIV prevalence

in high burden countries

0

400

800

1200

1600

0.0 0.1 0.2 0.3 0.4

HIV prevalence, adults 15-49 years

Est

imat

ed a

nn

ual

TB

in

cid

ence

(per

100

K a

du

lts,

199

9)

HIV prevalence increases by 1%TB incidence increases by 26/100k/yr

Williams B. 3rd Global TB/HIV Working Group Meeting; Montreux, 4-6 June 2003

Impact of HIV on TB in Africa

Notified cases per 100,000 pop. 1980-2008

4/5 of all estimated TB/HIV cases are in Africa

TB notification rate in 20 African countries* versus HIV prevalence TB notification rate in 20 African countries* versus HIV prevalence in sub-Saharan Africa, 1990–2004in sub-Saharan Africa, 1990–2004

Sources: World Health Organization (2006), Global TB database; UNAIDS (2006)

• Consistently reporting each year: Algeria, Angola, Botswana, Cameroon, Comoros, Congo, Côte d'Ivoire, Democratic Republic of Congo, Ghana, Guinea, Kenya, Malawi, Mauritius, Mozambique, Nigeria, Senegal, South Africa, Uganda, United Republic of Tanzania, Zimbabwe

0

20

40

60

80

100

120

140

160

180

200

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

0

1

2

3

4

5

6

7

8

TB notification rate

TB notification rate per 100,000 population

% Adult HIV prevalence (15-49)

HIV prevalence

4.5

Infection

with HIV

Infection with

M. tuberculosis

World Health Organization

Rich European Country

TB/HIV Co-infectionOverlap of two populations

Estimated HIV prevalence in new TB cases, WHO European Region 2008

TB in the HIV era

• Most frequent infection associated with HIV world-wide

• Can spread to the non-HIV population

• HIV can pull and steer the incidence of TB

16/03/2010: B V, male, 30 years old, from Romania, working in Italy since 4 years, is prescribed an HIV test because of genital lesions and oral candidiasis. The test result is positive.

3/05/2010: the patient develops persistent high fever and is admitted to the ward

Clinical case 1a

31/03/2010: His viro-immunological profile is as follows: CD4+ 173 (14,4%) HIV-RNA 106,000 copies. HIV treatment is prescribed: 3TC/ABC plus LPV/r.

A chest X-ray is performed (03/05)

Abdominal CT scan (07/05)

• TB suspect: sputum and blood samples examined – negative microscopy• M.tuberculosis isolated from sputum and blood on 24/05. Rapid

test for rifampicin resistance is negative.

• 25/05: TB treatment started with RIFABUTIN 150 mg every other day + INH/ETH/PZA; HAART is continued unchanged• 06/06: drug sensitivity testing available: resistance to isoniazid. The drug is removed and the TB regimen continues as planned

• The patient is fully adherent to monthly clinical visits, his conditions improves and normalise• 25/11: he completes TB treatment (6 months).

Disseminated TB diagnosed

Clinical case 1b

Key features of clinical case 1

• HAART is a significant determinant of the risk of TB in HIV infected persons

• Smear negative pulmonary TB and extrapulmonary TB is common

• Treatment of TB in an HIV infected person is challenging

TB and HIV in the era of HAART• HAART reduces the incidence of TB by approximately 80%

in high and low burden countries

• TB incidence in HIV infected persons receiving effective HAART is ~ 10 times higher than that in the background population

• HAART may unmask TB in persons with low CD4 cell count

• HAART may be key to control MDR epidemics among HIV infected persons

VariableAdjusted

Relative Hazard (95%CI)

P-value

HAART after TB Dx 0.45 (0.26-0.79) 0.005

CD4 < 200(Time- 200 – 349dependent) 350 – 499

≥ 500

10.46 (0.27-0.79)0.47 (0.26-0.85)0.32 (0.17-0.61)

0.0050.01

< 0.001

Sex MaleFemale

11.03 (0.67-1.60) 0.89

Age < 30 30-39 40-49 ≥ 50

10.85 (0.41-1.79)0.80 (0.38-1.69)0.26 (0.09-0.75)

0.670.560.01

Golub et al., AIDS 2008; 22:2527

Recurrent TB and ART in HIV-infected patients in Rio de Janeiro

N=1042 – recurrences in 8.9%

Changes in tuberculosis (TB) incidence during 3 years of HAART in Europe and North America with regression curve fitted. TB incidence rate is expressed as

number of cases per 1000 person-years of follow-up

Girardi E, Clin Infect Dis 2005, 41: 1772

Although the incidence tended to decrease with time, it was still 150 per 100,000 PYFU during the third year after starting HAART.Which is 10-fold higher than in HIV negative population

TB is the commonest illness among PLHIV on ART

Incidence of tuberculosis among HIV seropositive patients by timing after initiation of HAART

Dembele M, Int J Tub Lung Dis 2010, 14: 318

During the initial months of HAART incident TB cases may arise as a consequence of “unmasking” of

previously subclinical disease or the deterioration of a pre-existing disease

due to the reconstitution of the immune system (Lawn, 2005)

Incidence of tuberculosis among HIV seropositive patients by timing after initiation of HAART and

site of the disease

Dembele M, Int J Tub Lung Dis 2010, 14: 318

Lessons for HIV programmes

• Start ART at early stage (CD4 350 or below)

• Increase capacity to diagnose PTB by improved microbiological tools

• Increase capacity to diagnose EPTB (develop algorithms)

Improving diagnostic capacity

New(er) TB Diagnostic Tools

• Molecular assays – Cepheid GeneXpert– Hain GenoType MTBDRplus)

• LED fluorescent microscopy

• Liquid culture (e.g. MGIT)– Sensitivity ~50-75% > L-J

• Capilia TB– Rapid strip test that detects a TB-specific antigen from culture

LED microscopy

Liquid cultureMolecular assays

Boehme et al. N Engl J Med 2010; 363: 1005

Xpert MTB/RIF

Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive TB (98.2%)

and 124 of 171 with smear-negative TB (72.5%). The test was specific in 604 of 609 patients without

tuberculosis (99.2%).MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514

(98.1%) with rifampin-sensitive bacteria.

Proportion of TB cases detected and time to detection

Courtesy of C Gilpin

Current understanding of Xpert TB contribution to TB control

• Increases sensitivity of 30% compared to miscroscopy

• Reduces time to start TB treatment• Might have an impact on mortality• Logistic is manageable• Costs per TB case detected increases x 3 times but

remains cost-effective with WHO criteria (<1 GDP/capita)

• Impact on EPTB and pediatric TB under investigation

Treatment of TB in HIV infected persons

Strategy for initiation of TB treatment in HIV infected patients with active TB

TB treatment should be started immediately under all circumstances

WHO, 2010: Rapid Advice on ART

Treatment of Tuberculosis in HIVDaily or 3 times weekly therapy only

Isoniazid

Rifampin

Pyrazinamide

Ethambutol

0 1 2* 3 4 5 6 7 8 9months

Initial Phase Continuation Phase*

*If culture positive at 2 months and cavitation, extend therapy to 9 months

CDC , ATS and Infectious Diseases Society of America Guidelines

Does 6-month therapy duration increase the risk of relapse ?

DURATION OF

RIFAMPIN

N. STUDIES N. RELAPSES

POOLED RELAPSE RATE

(95% CI)

aRR(95% CI)

2 months 6 40/258 10,8 (0-25,1) 3,6 (1,1-11,7)

6 months 12 100/730 9,8 (0-19,8) 2,4 (0,8-7,4)

> 8 months 6 20/314 3,3 (0-9,0) 1,0 (reference)

Pooled estimate of relapse result stratified by duration of rifampin

Khan FA, AIDS 2010 (methanalysis)

Programmatic outcomes for TB/HIV patients are poor

WHO Global TB Report, 2009

Choice of HIV drugs

ART for HIV/tuberculosis co-infection

WHO recommendation

• Use efavirenz as the preferred non nucleoside reverse transcriptase inhibitor in patients starting ART while on treatment

(strong recommendation – High quality of evidence)

WHO, 2010: Rapid Advice on ART

Efavirenz, no doubtsAdvantagesIs a first line option for HIV treatment

In the most widely used first line drug in resource limited settings

Allows for standard TB therapy

Allows for once a day therapy with minimal pill burden (Atripla)

Clinical trials available from South Africa and Thailand

EFV dose in TB/HIV co-infection treated with RMP (600 versus 800 mg)

• Reduction in EFV levels:20-25%

• Clearance of EFV lower in in Afro-Americans and Hispanics than Caucasians (impact on safety profile); body weight also important (60 kg threshold)

• In Caucasian > 60 Kg EFV 800 mg + RIF give AUC similar to EFV 600 mg

• In Thailand and South Africa studies show effective, pharmacological, clinical, immunological and virologic response with conventional 600 mg EFV dose

Effect of RFM on Serum Concentrations of PIs and NNRTI

PI

Saquinavir

Ritonavir

Indinavir

Nelfinavir

Amprenavir

Lopinavir/ritonavir

Atazanavir

80%

35%

90%

82%

81%

75%

not done

NNRTI

Nevirapine

Efavirenz

37-58%

13-26%

What if efavirenz cannot be used ?

Available data allows for the use of LOPINAVIR, ATAZANAVIR, FOSAMPRENAVIR, DARUNAVIR, TIPRANAVIR always with RITONAVIR boosting

Rifabutin and HIV drugs of the PI class

Ritonavir increases rifabutin levels significantly, requiring a dose reduction to 150 mg every other day (DHHS)This recommendation is derived from PK studies in healthy volunteers

PI blood level adequate to ensure efficacy (but few datafrom clinical trials)

Rifabutin 150 mg every other day in association with Lopinavir/r

• 9/10 patients with low Cmax values (<30g/ml) (Boulanger C, CID 2009

Khaci H, JAC 2009)

• 5/5 patients with low Cmax values (<45g/ml)

Naiker S, 18° ICAAR, 2011

• AUC significantly reduced compared to the standard in 16 TB/HIV patients in South Africa. AUC reverted by 150 mg daily during LPV/r treatment

Ryfamicin resistance

• Monoresistance described almost exclusively in HIV infected patients

• Associated with intermittent ryfamicin use (rifapentine, probably for low drug blood levels)

Rifabutin low blood levels may carry a risk for selection of rifamycin-resistant M.tuberculosis

Current dosing recommendation for rifabutin in association with LPV/r likely to need revision

Drug Interactions: Rifampicin and other HIV drugs

• NNRTIs– Rifampicin decreases Etravirin exposure

“significantly”. Combination not recommended• CCR5 Inhibitors

– Rifampicin reduces maraviroc exposure by 63%. Maraviroc doses could theoretically be doubled but no clinical experience

• Integrase inhibitors– Rifampicin reduces raltegravir exposure by 40-60%.

Raltegravir 800 mg BID suggested, but optimal concentration range of this drug is unknown

Drug Interactions: Rifabutin and other HIV drugs

• NNRTIs– No significant interactions with efavirenz and

nevirapin (but no advantage over rifampicin). With efavirenz rifabutin dose need to be increased to 450 mg daily

• Integrase inhibitors– Rifabutin does not alter raltegravir exposure to

a clinically meaningful degree (Brainard DM et al. J Clin Pharmacol 2010)

• CCR5 Inhibitors– No clinical data

C. L. female, 27 years old, originating from Dominican Republic. Known HIV infection since 2005. HBV/HDV co-infections. Default from follow-up and HAART in 2007.

On 06/07/2010 admitted to the clinical ward for fever and cough since three months, irresponsive to antibiotic therapy.

A chest X-ray is performed:

Clinical case 2a

Sputum examination: AFB seen, Pneumocystis jirovecii seenMolecular test: M.tuberculosis, no resistance markers to rifampicin

Smear positive pulmonary TBPCP

CD4 cell count = 27; HIV-RNA 157,000 copies

Discharged on 03/08 in good clinical conditions and no signs of toxicity

On 07/07 starts standard antituberculosis treatment with Rimstar 4 tabs /day

On 26/07 starts HAART using TDF/FTC plus + EFV 800 mg once a day

Clinical case 2b

On 16/08 admission to the clinical ward for re-emergence of high fever and cough since 3 days. A lung CT is performed.

Clinical case 2c

Adherence to TB treatment reported as optimal. Drug-sensitive TB

Concomitant opportunistic infections ruled out

Other bacterial infections not detected

CD4 cell count = 54; HIV-RNA 600 copies

On 20/08 metilprednisolone 1,5 mg / Kg /day was started

On 01/09 the patient is discharged afebrile, in good clinical conditions, continuing TB, ARV and steroid treatment at home

Clinical case 2d

Key features of clinical case 2

• Do TB/HIV patients need ART ?• Timing of ARV in TB/HIV patients• The risk of the immune reconstitution

syndrome (IRIS) and its relevant characteristics

• Management of the IRIS

Do TB/HIV patients need ART ?

SAPiT Trial: Initiating ART during TB treatment significantly increases survival

ART initiation during TB treatment(n = 429)

ART initiation after TB treatment (n = 213)

HIV-pos with TB and CD4+ < 500 cells/mm3

(N = 642)

Median 67 days

Median 261 days

Primary Endpoint: mortality rate (any cause)

Abdool Karim SS, N Engl J Med 2010; 362:697-706

Timing of Initiation of Antiretroviral Drugsduring Tuberculosis Therapy: the SAPiT trial

Abdool Karim SS, N Engl J Med 2010; 362:697-706

• HR for mortality in arm A = 0.45 (0.26 – 0.79) p=0.005 for any CD4

• HR = 0.54 for CD<200• HR = 0.08 for CD4>200Trial stopped by the ethical committee

Timing of ART in HIV/tuberculosis patients

WHO recommendation

• Start ART in all HIV infected individuals with active tuberculosis irrespective of CD4 cell count

(strong recommendation – Low quality of evidence)

WHO, 2010: Rapid Advice on ART

Timing for ARV in TB patients

CONCLUSION: Mortality was reduced by 34% when HAART was initiated 2 weeks vs 8 weeks after onset of TB treatment

Early (2 weeks) vs. late (8 weeks) initiation of HAART: the CAMELIA study (Blanc et al).

Kaplan-Meier Survival curve

Timing of ART during TB therapyTrial Sites and

patientsStudy design and

endpointOverall results

Results in CD4<50

ACTG 5221 STRIDE study(1)

Multicentre in 4 continents (majority in Africa).

TB suspect or confirmed <250 CD4

Immediate (2 w) Vs. early (8 w)

Death+AIDS events at W48

13.0% Vs.16.1%P=0.45

15.5% Vs. 26.6%

P=0.02

SAPiT continuation phase(2)

One centre in South Africa

Smear+PTB<500 CD4

Early (1-4 w) Vs. late (8-12 w)

Death+AIDS events at W48

6.9 Vs. 7.8 /100 p-yP=0.73

8.5 Vs. 26.3 /100 p-y

P=0.06

(1) Havlir D, et al. Abs 38, 18° CROI, Boston 2011(2) Abdool Karim S, et al. Abs 39LB, 18° CROI, Boston 2011

The Camelia study: the median of the CD4 cellc count of enrolled patients was 25 cells

STRIDE and SAPiT trials: for CD4> 50 there was no trend towards decreased death/AIDS events

ART Initiation in TB Meningitis – A Randomized Trial in Vietnam

• Immediate – ART within 7 days after TB initiation

• Deferred – ART initiated 2 months after TB initiation

Immediate Deferred

Number 127 126

Died 76 70

Survival 40% 45%

p=0.52

Torok et al. ICAAC 2009, Abstract H-1224

Timing of ART in HIV/tuberculosis patients

WHO recommendation

• Start TB treatment first, followed by ART as soon as possible after starting TB treatment

(strong recommendation – Moderate quality of evidence)

WHO, 2010: Rapid Advice on ART

Optimal timing of ART among TB patients – what is the evidence ?

• ART should be started within 2 weeks from TB therapy in TB/HIV patients with CD4 < 50

• ART can be delayed up to the end of the intensive phase of TB treatment in TB/HIV patients with CD4>50

What if CD4 cannot be measured – or timely measured ? Unclear at this time

Expected mortality should steer decision on optimal timing of combined TB and

HIV therapy

Risk of death while awaiting

HAART

Risk of death as a consequence of HAART (IRIS)

Combined HAART and treatment for tuberculosis

ConstraintsIncreased rate of paradoxical reactions (IRIS)

Additive toxicity

Reduced adherence

Operational delays

Definition of IRIS(A) Antecedent requirements• Diagnosis of tuberculosis before starting ART • Initial response (stabilised or improved) to tuberculosis treatment

(B) Clinical criteria• Onset of manifestations within 3 months of ARTPlus at least one major or two minor criteria Major criteria1) New or enlarging lymph nodes, or similar cold abscesses, 2) New or worsening

radiological features of TB; 3) New or worsening CNS TB; 4) New or worsening serositis

Minor criteria1) New or worsening constitutional symptoms; 2) New or worsening respiratory

symptoms; 3) New or worsening abdominal pain

(C) Alternative explanations for clinical deterioration must be excluded if possible

• Failure of tuberculosis treatment because of tuberculosis drug resistance• Poor adherence to tuberculosis treatment• Another opportunistic infection or neoplasm• Drug toxicity or reaction

Meintjes G et al. Lancet ID 2008; 8-516

TB IRIS

Do patients die because of IRIS ?

Muller M, Lancet Infect Dis, 2010 10: 251 (metanalysis)

3·2% (0·7–9·2) of patients with tuberculosis-associated IRIS died

Management of IRIS

• Make certain of diagnosis– Rule out MDR TB or new opportunistic infection

• TB treatment should be continued • ARV treatment should be continued • Surgical drainage• Non-steroidal anti-inflammatory drugs• Steroids – 1.5 mg/kg prednisone

Corticosteroids and IRIS outcome• 109 TB/HIV patients with clinical definition of IRIS in South

Africa• Randomised, placebo controlled trial of 1.5 mg/kg/day (2

weeks) + 0.75 mg/kg/day (2 weeks)• Cumulative # hospital days 282 Vs. 463 • Median # hospital stay 1 Vs. 3 (p=0.05)

Meintjes G, AIDS, 2010

Overlap of Adverse Reactions from Drugs Used to Treat TB and HIV Infection

Adverse Reaction TB Drugs HIV Drugs

Rash PZA, RIF, INH NNRTIs, ABC, T/S

Hepatotoxicity INH, RIF, PZA PIs, NVP

Nausea RIF, PZA, INH RTV, AZT, APV

Cytopenias RBT, RIF AZT, T/S

CNS INH EFV

• Most studies demonstrate an increased rate of side effects during TB therapy among HIV infected persons

• In randomised trials of combined TB and HIV therapy, toxicity was a very unlikely cause of treatment discontinuation

Side effects of TB treatment and HIV infection

ART in TB patients by Region, 2008

Region started on ART

AFR 30%AMR 67%EMR 55% EUR 29% SEAR 35%WPR 28%

Operationalising ART in TB patients

• Rapid HIV diagnosis• Rapid CD4 determination (or identificatioon of

surrogate markers – BMI,Hb, clinical or radiological signs)

• Avalability of ART (often requires referral and loss during referral or delay)

• Instruct on how to identify and manage IRIS• Prevention of IRIS ?

Prevention of HIV associated TB

- Early diagnosis- IPT- ARV

Policies for regular TB screening among PLWHA

• Educating health workers to early recognition of TB symptoms in PLWHA

• At every consultation in chronic HIV care:– Searching for signs (cough)– Searching for symptoms (clinical examination)

• If necessary: second level investigations (sputum microscopy, Chest X-ray)

WHO 2010 IPT/ ICF recommendations

Does the WHO algorithm for Screening HIV Patients work ?

• Presence of symptoms – work up for TB– Sensitivity 79%– Specificity 56%

• Absence of symptoms – proceed with INH preventive therapy– Negative predictive value 97%

Getahun H et al. Plos Med 2011; in press

Treatment of latent tuberculosis infection

Current standard (IPT):

• Isoniazid 300 mg /daily for 6-9 months

Efficacy of IPT compared with

placebo, in reducing the incidence of

active TB

Akolo C, et al. Cochrane Review, 2010

Treatment of latent tuberculosis infection

Research perspectives:• Shorter regimens• Drugs with no baseline resistance • Well tolerated

In high burden countries, where risk of re-infection is high:

• Operationalising IPT

Efficacy of 36 vs. 6 months of INH for HIV-infected Adults in Botswana

The BOTUSA Trial

Samandari et al., IUATLD Conference, December 2009

Can IPT increase resistance to INH ?

• There is no evidence that IPT can increase resistance to INH provided that active disease is ruled out

• Directly observed administration of INH is not essential, although poor adherence will limit the impact of IPT

Is IPT safe ?

The Botswana NTP / CDC IPT study • Of 1,762 patients in analysis 19 (1.2%) developed

hepatitis (grade 3 or above). One patienst died. (1) • Low rate of severe adverse events after the first six

months of IPT: 7 (0.9%) in the 6-IPT arm (placebo) and 11 (1.3%) in the 36-IPT arm (2)

• Coadministration with ART slightly increased liver toxicity (RR 1.59 [0.63-4.0]). Risk greater on nevirapine (RR 2.09 [0.74 - 5.87]) than efavirenz (RR 0.96 [0.21 - 4.31]).

1. Tedia Z et al, Am J Respir Crit Care Med 2010; 182:2782. Samandari T, 40 IUATLD Conference, Cancún, 2009

Clinical monitoring appropriate for safety of IPT

Eligibility for IPT

In areas of high prevalence of TB (>30% infected): All HIV infected individuals who are not affected by active

TB

In areas of lower prevalence of TB (<30% infected): HIV infected individuals with a positive PPD test who are

not affected by active TB

Independently from CD4 cell count

Samandari et al., IUATLD Conference, December 2009

36 vs. 6 months of INH for HIV-infected Adults in Botswana -The BOTUSA Trial

The probability of a positive TST test is associated to the level of immune suppression

Elzi et al CID 2007

Do IGRAs help for screening of LTBI in HIV+ subjects ?

Current evidence suggests that IGRAs perform similarly to the tuberculin skin test at identifying HIV-infected individuals with latent tuberculosis infection. Given that both tests have modest predictive value and suboptimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistic considerations.

Cattamanchi A, et al. JAIDS 2011; 56:230-8

TB Rates by ART and INH Treatment Status, 2003-2005

Exposure category Person-Years TB Cases Incidence Rate

(per 100 PYs)

PercentReduction(95% CI)

No Rx 3,865 155 4.01 (3.40-4.69) -

ART only 11,627 221 1.90 (1.66-2.17) 52%(41-61%)

IPT only 395 5 1.27 (0.41-2.95) 68%(24-90%)

Both 1,253 10 0.80 (0.38-1.47) 80%(9-91%)

Total 17,140 391 2.28 (2.06-2.52)

Golub et al., AIDS 2007;21:1441-8

Exposure category

Person-

years

TB case

s

Incidence rate (per 100 PYs)

(95% CI)

Incidence rate ratio (95% CI)

Adjusted hazard ratio*

(95% CI)

Naïve 2815 200 7.1 (6.2-8.2) REF REF

HAART only

952 44 4.6 (3.4-6.2)0.65 (0.46-

0.91)0.36 (0.25-

0.51)

INH only 427 22 5.2 (3.4-7.8)0.73 (0.44-

1.13)0.87 (0.55-

1.36)

Both 93 1 1.1 (0.2-7.6)0.15 (0.01-

0.85)0.11 (0.02-

0.78)

TOTAL 4287 267 6.2 (5.5-7.0)

TB Rates by ARV and INH Treatment Status in South African Adults with HIV Infection

* Adjusted for age, sex, CD4, prior history of TB, urban/rural

Golub et al, AIDS 2009;23:631-6

New TB screening and IPT guidelines

• TB screening and IPT in tandem• Symptom based clinical algorithm for TB

screening developed: 4 simple questions• INH for 6 (strong) and 36 (conditional)

months recommended• Pregnant women, children and people

receiving ART included• TST is not a requirement• Should be a core function of HIV services

WHO recommended TB/HIV collaborative activities

A. Establish NTP-NACP collaborative mechanisms Set up coordinating bodies for effective TB/HIV activities

at all levels Conduct surveillance of HIV prevalence among TB cases Carry out joint TB/HIV planning Monitor and evaluate collaborative TB/HIV activities

B. Decrease burden of TB among PLHIV (the "3 Is") Establish Intensified TB case finding Introduce INH preventive therapy Ensure TB Infection control in health care and congregate

settings

C. Decrease burden of HIV among TB patients Provide HIV testing and counselling Introduce HIV prevention methods Introduce co-trimoxazole preventive therapy Ensure HIV/AIDS care and support Introduce ARVs

Policy on collaborative TB/HIV activities WHO recommendations 2004

A. Establish the mechanism for integrated TB& HIV services Set up coordinating bodies for effective TB/HIV activities

at all levels Conduct surveillance of HIV prevalence among TB cases Carry out joint TB/HIV planning Conduct monitoring and evaluation

B. Decrease burden of TB among PLHIV (the "3 Is") Establish Intensified TB case finding and ensure quality TB treatment Introduce TB prevention with IPT or ART Ensure TB Infection control in health care and congregate

settings

C. Decrease burden of HIV among TB patients Provide HIV testing and counselling to TB suspects & TB patients Introduce HIV prevention methods for TB suspects & TB patients Provide CPT for TB patients living with HIV Ensure HIV prevention; treatment & care for TB patients with HIV Introduce ARVs to TB patients living with HIV

World Health OrganizationWorld Health Organization

The 12 points package: what is new?

HIV case finding among TB:

• HIV testing coverage = 79% (~ 357.000 patients)• HIV prevalence among tested TB = 3% (~ 11.500

patients)• Estimated HIV prevalence = 5.6% (~ 23.800 people) • 48% of TB/HIV patients are detected

TB/HIV co-infection, WHO European Region 2008

TB/HIV co-infection, WHO European Region 2008

Management of TB/HIV co-infected patients:• 61 % of TB/HIV patients are covered by CPT• 9.2 % covered by IPT• 29% of TB/HIV patients are covered by ARV

treatment

TB/HIV co-infection, WHO European Region 2008

TB case finding among PLHIV:• estimated TB prevalence among PLHIV = 1.7%• screening coverage for TB = ??? (~205 000)

The Health Structure

1. Extreme verticality of the TB and AIDS programmes both in service provision and management;

2. Lack of effective coordinating mechanisms for TB and HIV

Challenges and response

TB/HIV/IVDU convergence

Challenges and response

TB/HIV in marginalised populations

Challenges and response

Prisoners

Migrant people

Increasing convergence of drug resistant TB and HIV in the region and the lack of understanding of the extent of the problem.

Efforts to address drug resistant TB in the region need to be scaled up and integrated with HIV prevention and treatment services.

TB/HIV Working Group of the Partnership Focus on European Region, Almaty, May 2010

Convergence of TB/HIV and MDR-TB

Challenges and response

Outcomes of Treatment for MDR TB in the South African DOTS-Plus Program, 2002-2004

Outcome HIV + (N=327)

HIV –/unknown(N=875)

P value

Successful Rx 38.5% 49.3% <0.001

Failed 4.3% 11.4% <0.001

Defaulted 21.4% 22.6% 0.65

Died 35.8% 16.7% <0.001

Farley, van der Walt, et al., IUATLD World Conference, 2007

Thank you for your attention