1 tuberculosis and hiv haivn harvard medical school aids initiative in vietnam
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Tuberculosis and HIVHAIVN
Harvard Medical School AIDS Initiative in Vietnam
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Learning Objectives
By the end of this session, participants should be able to:
Explain the significance of TB/HIV co-infection
Describe the clinical presentation of TB in PLHIV
Outline TB treatment regimens Explain drug-resistant TB Describe common interactions between
ARV and TB drugs
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TB Epidemiology (1)
Vietnam is ranked 12th in the world for incident TB
The incidence in the general population is 180/100,000
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TB Epidemiology (2) Global TB Control.WHO 2010
Vietnam
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TB / HIV EpidemiologyGlobal TB Control.WHO 2010
Vietnam
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TB/HIV Interaction (1)
TB is the most common OI in developing countries and the most common cause of death among HIV patients
TB infection:• speeds the progression of HIV by increasing
viral replication• worsens immunological suppression in HIV
patients HIV increases mortality among patients
with TB
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TB/HIV Interaction (2)
Most TB cases are caused by reactivation of latent TB infection
In Vietnam, an estimated 50-60% of the population has latent TB infection
HIV greatly increases the chance for latent TB infection to become active
Status Risk of active TB infection
HIV negative 10% lifetime risk
HIV negative IDU
1% risk per year
HIV infected 10% risk per year
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Clinical Presentation of PLHIV with TB
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HIV worsens the signs and symptoms of TB, as shown in the chart
The Effects of HIV on TB
Symptom /Sign HIV Positive HIV Negative
Dyspnea 97% 81%
Fever 79% 62%
Sweats 83% 64%
Weight loss 89% 83%
Diarrhea 23% 4%
Hepatomegaly 41% 21%
Splenomegaly 40% 15%
Lymphadenopathy 35% 13%
Ref: Chest 1994;106:1471-6
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Clinical Presentation and CD4 (1)
Correlation Between Extent of HIV-Induced Immuno-Suppression and Clinical Manifestation of Tuberculosis
Duration of HIV infection
Med
ian
CD
4 c
ell
co
unt /
mm
3
0
100
200
300
400
500
De Cock KM, et al. J Am Med Assoc 1992;268:1581-7
Pulmonary tuberculosis
Lymphatic, serous tuberculosis
Tuberculous meningitis
Disseminated tuberculosis
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Clinical Presentation and CD4 (2)
CD4 > 500 • “Typical” presentation: • Fever• Cough• Weight loss• Bloody sputum
CD4 < 200 • “Atypical” presentation: • fever of unknown etiology• weight loss• minimal cough
• Extra-pulmonary disease more likely• Sputum sample more likely to be negative
Signs and Symptoms of Pulmonary TB
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Typical Chest X Ray
Early stages of HIV (CD4 > 500): Infiltrates predominantly in upper lobes Pulmonary cavities present Pleural effusions
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Atypical Chest X Ray
Advanced stages of HIV (CD4 < 200):
Pulmonary cavities absent
Infiltrates in middle and lower lobes
Nodular infiltrates Effusions can be
pleural and pericardial
Mediastinal lymphadenopathy with no pulmonary infiltrates
Normal CXR in 10 %
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Chest X Ray – Miliary (Disseminated) TB
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Extra-pulmonary TB (1)
Extra-pulmonary Tuberculosis (EPTB) occurs when bacteria spread outside of the lung and cause disease• Occurs more commonly in people with
weak immune systems e.g. PLHIV• May occur with or without concomitant
pulmonary TB
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Extra-pulmonary TB (2)
Occurs most often when a person’s CD4 < 100
Most commonly manifests as:• Abdominal and lymph node TB (very often)• TB meningitis (5-10%), Tuberculoma• Pericarditis• Pleural effusion• Cutaneous• Renal
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Extra-pulmonary TB (3)
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Extra-pulmonary TB (4)
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Sputum Smear and HIV Status (1)
Diagnose TB by examining stained sputum samples for presence of acid fast bacilli (AFB)
Sputum smear is the most rapid and inexpensive diagnostic test for TB
The sensitivity of TB sputum smears depends on many factors including HIV status
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Sputum Smear and HIV Status (2)
Tubercle Lung Dis 1993;75:191-4
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TB HIV Co-infection Key Clinical Practice Points
“Typical” pulmonary TB less common
“Atypical”, smear negative and extra-pulmonary TB more common• WHO and Vietnam MOH guidelines allow
TB treatment on clinical suspicion without positive smear test
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MOH and WHO Recommend: “THE ANTIBIOTIC TRIAL”
When indicated, use one course of broad spectrum antibiotics including coverage for typical and atypical causes of community acquired pneumonia
Under such circumstances, avoid Fluoroquinolones to prevent undue delay in diagnosis of TB
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Treatment Regimens for PLHIV with TB
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TB National Treatment Protocol (1)
Drug DosageIsoniazid (H) 5 mg/kg/day
Rifampin (R) 10 mg/kg/day
Pyrazinamide (Z) 20-30 mg/kg/day
Streptomycin (S) 15 mg/kg/day
Ethambutol (E) 15-25 mg/kg/day
Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.
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TB National Treatment Protocol (2)
For newly diagnosed TB cases, regimen 1:
2 S(E)HRZ / 6 HE 2 S(E)RHZ / 4 RH*
* applied only if direct observation continued in maintenance phase
Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.
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TB National Re-Treatment Protocol (3)
For recurrent TB and failure to Regimen 1, there is Regimen 2:• 2 SHRZE for 2 months: 5 drug
THEN• 1 HRZE for 1 month: 4 drugs
THEN• 5 H3R3E3 for 5 months: 3 drugs given 3
times per week Total duration: 8 months
Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, Vietnam. 2009.
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TB Treatment: Special Situations
Some special situations require a more aggressive course of treatment, including:• Miliary TB• Pericarditis• Meningitis• Spondilitis with
neurological complications
For pregnant women: avoid streptomycin - can cause permanent deafness in baby• Use ethambutol
instead
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Small Group Activity: Case Study 1
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Drug Resistant TB (1)
Type MeaningMono-resistance Resistant to only 1 anti-TB drug
Poly-resistance (PDR)
Resistant to more than 1 anti-TB drug, but not INH and RIF combination
Multi-drug resistance (MDR)
Resistant to at least INH and RIF, the 2 most effective anti-TB drugs
Extensively drug-resistant (XDR)
MDR and further resistance to any fluoroquinolone and at least one of three injectable second-line drugs: amikacin, kanamycin, or capreomycin
Drug resistant TB is TB for which anti-TB drugs have little or no effect against the TB causing agent
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Drug Resistant TB (2)
Causes of drug resistant TB include: Inadequate treatment regimens Interrupted availability to drug
treatment Poor quality of drug treatment Incomplete treatment adherence Results from spontaneous mutations
of MTB exposed to drugsQuy HT, Buu TN et al Int J Tuberc Lung Dis 2006;10(2):160-166.
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Multi Drug-Resistant (MDR) TB in Vietnam
Among reported cases in 2008, it is estimated that:• 2.7% of new TB cases had MDR-TB• 19% of re-treatment cases had MDR-TB
3500 MDR-TB cases among reported pulmonary TB cases in 2009
Global TB Control. WHO 2010
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TB and ARV Drug Interactions (1)
ARV Effect Treatment/Solution
NVP 37%Switch to EFV, if available
(NVP OK, if necessary*)
EFV 25% EFV still effective
PI
(LPV/r, IDV) 80-90%
Do not use PI with RIF: refer to specialty center for treatment
• Rifampicin decreases drug levels of some ARVs:
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TB and ARV Drug Interactions (2)
TB ARV Toxicity
INH d4T
Peripheral neuropathy: prevent with pyridoxine (B6)
25-50 mg/day
INH, RIF, PZA
NVP, EFV Hepatotoxicity
Note overlapping toxicities of TB and ARV drugs
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Case Study 2 (1)
26 year old patient with HIV and a CD4 count of 15 presents with prolonged fever and wasting
CXR shown to right You suspect TB but
sputum AFB/BK is negative
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Case Study 2 (2)
What does the CXR show?
How do you interpret negative sputum smear?
How would you manage the patient?
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Key Points
TB/HIV co-infection is common among PLHIV in Vietnam
HIV infection increases risk for active TB infection by over 100 fold
Clinical presentation of TB varies by CD4 count
TB treatment regimens are the same for both HIV+/- patients
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Thank you!
Questions?