tb and hiv: from clinical practice to public health action alberto matteelli institute of infectious...
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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
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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
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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
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Infection
with HIV
Infection
with
M.
tuberculosis
Sub-Saharan African country
TB/HIV Co-infectionOverlap of two populations
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Estimated HIV prevalence in new TB cases, 2009
WHO, Global TB report 20101.1 million TB/HIV cases and 400,000 deaths
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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
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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
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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
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Infection
with HIV
Infection with
M. tuberculosis
World Health Organization
Rich European Country
TB/HIV Co-infectionOverlap of two populations
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Estimated HIV prevalence in new TB cases, WHO European Region 2008
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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
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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.
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A chest X-ray is performed (03/05)
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Abdominal CT scan (07/05)
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• 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
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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
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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
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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%
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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
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TB is the commonest illness among PLHIV on ART
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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)
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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
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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)
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Improving diagnostic capacity
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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
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LED microscopy
Liquid cultureMolecular assays
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Boehme et al. N Engl J Med 2010; 363: 1005
Xpert MTB/RIF
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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.
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Proportion of TB cases detected and time to detection
Courtesy of C Gilpin
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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
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Treatment of TB in HIV infected persons
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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
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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
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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)
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Programmatic outcomes for TB/HIV patients are poor
WHO Global TB Report, 2009
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Choice of HIV drugs
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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
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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
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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
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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 ?
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Do TB/HIV patients need ART ?
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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
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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
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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
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Timing for ARV in TB patients
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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
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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
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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
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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
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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
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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)
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Combined HAART and treatment for tuberculosis
ConstraintsIncreased rate of paradoxical reactions (IRIS)
Additive toxicity
Reduced adherence
Operational delays
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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
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TB IRIS
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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
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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
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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
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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
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• 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
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ART in TB patients by Region, 2008
Region started on ART
AFR 30%AMR 67%EMR 55% EUR 29% SEAR 35%WPR 28%
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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 ?
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Prevention of HIV associated TB
- Early diagnosis- IPT- ARV
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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
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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
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Treatment of latent tuberculosis infection
Current standard (IPT):
• Isoniazid 300 mg /daily for 6-9 months
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Efficacy of IPT compared with
placebo, in reducing the incidence of
active TB
Akolo C, et al. Cochrane Review, 2010
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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
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Efficacy of 36 vs. 6 months of INH for HIV-infected Adults in Botswana
The BOTUSA Trial
Samandari et al., IUATLD Conference, December 2009
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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
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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
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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
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Samandari et al., IUATLD Conference, December 2009
36 vs. 6 months of INH for HIV-infected Adults in Botswana -The BOTUSA Trial
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The probability of a positive TST test is associated to the level of immune suppression
Elzi et al CID 2007
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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
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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
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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
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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
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WHO recommended TB/HIV collaborative activities
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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
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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?
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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
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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
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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)
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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
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TB/HIV/IVDU convergence
Challenges and response
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TB/HIV in marginalised populations
Challenges and response
Prisoners
Migrant people
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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
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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
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Thank you for your attention