Tuberculosis and HIV potx

• Give the treatment regimens for pulmonary and extrapulmonary TB • Describe the factors that increase resistance in TB patients in Vietnam... Outline of Talk• TB/HIV epidemiology in V

Tuberculosis and HIV

VCHAP

Vietnam-CDC-Harvard Medical School

AIDS Partnership

• Describe the natural history and clinical

presentations of the HIV + patient with TB

in comparison to the HIV – patient with TB

• Give the treatment regimens for

pulmonary and extrapulmonary TB

• Describe the factors that increase

resistance in TB patients in Vietnam

Outline of Talk

• TB/HIV epidemiology in Vietnam

• Clinical manifestations of TB in the

PLWHA

• Diagnosing Pulmonary and

Extrapulmonary TB in the PLWHA – WHO

2006 Guidelines

• Treatment of Pulmonary and

Extrapulmonary TB in the PLWHA

• TB drug resistance in Vietnam

Incidence of Active TB in Persons with

Positive Tuberculin Skin Test

person-years

TB infection < 1 year ago 12.9

TB infection 1-7 years ago 1.6

HIV + Injection Drug User 76

HIV – Injection Drug User 10

Louie JK, Nguyen HC et al Inter Jrnl of STD & AIDS 2004;15:758 - 761

*50% of pts with this diagnosis, grew + cultures for MTB

OI distribution in 220 HIV/AIDS inpatients at

Clinical Presentation of the PLWHA with Tuberculosis

The effect of HIV infection on signs

81 62 64 83 4 21 15 13

Clinical presentation and CD4

• Patients with mild

immunosuppression (CD4 > 500) are more likely to present with signs and symptoms of

pulmonary TB

– cough with or without bloody sputum

– upper lobe disease, cavitations

– pleural effusions

– fever, weight loss etc

Clinical presentation and CD4

• Patients with advanced

immunosuppression (CD4 <

200) have more atypical

symptoms:

– fever, weight loss with minimal cough

– AIDS w asting syndrome

– extrapulmonary disease

– atypical chest radiographs

– smear negative tuberculosis

Sputum smear and HIV status

Tubercle Lung Dis 1993;75:191-4

Chest XRAY findings in patients with TB/HIV

Early stages of HIV (CD4 > 500)

• infiltrates predominantly in upper lobes

• pulmonary cavities present

• pleural effusions

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

Diagnosing Tuberculosis in

the PLWHA

WHO 2006 Case Definitions for

Tuberculosis

New Perspectives on the Case Definition of

Tuberculosis

• In the 2006 WHO guidelines, the HIV status

of the patient is a key component of the TB case definition.

• In the 2006 WHO guidelines, HIV

prevalence in the community determines the management of the patient being

evaluated for TB

2006 WHO case definition

Smear positive pulmonary TB (SPPTB)

• Two or more initial

sputum smear

examinations positive

for AFB

or

• One sputum smear

examination positive for

AFB PLUS radiographic

abnormalities consistent

with active PTB as

determined by a clinician

or

• One sputum smear

positive for AFB PLUS

sputum culture positive

or

• Strong clinical

evidence of HIV infection.

2006 WHO case definition

Smear negative pulmonary TB (SNPTB)

• At least three negative

sputum specimens for

• At least two negative sputum

specimens for AFB and

• Radiographic abnormalities

consistent with active TB and

• Laboratory confirmation of

HIV infection OR

• Strong clinical evidence of

HIV infection and

• Decision by a clinician to

treat with a full course of anti-TB chemotherapy

OR

• A patient with AFB smear

negative sputum which is culture positive for

Mycobacterium tuberculosis

• Histological or strong

clinical evidence consistent with active extrapulmonary TB and

• Laboratory confirmation of

HIV infection

OR

• Strong clinical evidence of

HIV infection and

Evaluation and Management of the

PLWHA suspected to have

Tuberculosis

New WHO Perspectives on the Evaluation and Management of the PLWHA suspected to have TB

• Now, a setting with high HIV prevalence

determines the management of the

patient

• An HIV prevalent setting is defined as:

– Adult HIV prevalence rate among pregnant women is ≥ 1% or HIV

prevalence among TB patients is ≥ 5%.

– Setting : country, sub-national administration unit (e.g., district, county), selected facility (e.g., referral hospital, drug rehabilitation centre)

• For countries with national HIV prevalence

< 1%, national TB and HIV authorities

should identify and define HIV prevalent settings

Key WHO recommendations in 2006

• Algorithms are tailored to clinical condition

• HIV testing to TB suspects along with AFB

• Acceptable number of visits established

• CXR and Culture to be done earlier

Key WHO recommendations in 2006

• Vigilance and flexibility to start empiric

treatment for suspected extrapulmonary

TB in peripheral health facilities

• TB care should include HIV care

– HIV staging (clinical , immunological)

– PCP treatment

– Co-trimoxazole preventive therapy

• Clinical management of extrapulmonary

TB be included as TB control programme activity

• Recording and reporting of Smear

Negative TB improved

Key 2006 WHO Recommendations for Smear negative

TB (SNPTB) and/or Extrapulmonary TB (EPTB):

“THE ANTIBIOTIC TRIAL”

• “When indicated, one course of broad

spectrum antibiotics including coverage for

typical and atypical causes of community

acquired pneumonia, should be used to

reduce the time delay to TB diagnosis.”

• “Under such circumstances,

Fluoroquinolones should be avoided to

prevent undue delay in the diagnosis of TB

“

Key 2006 WHO Recommendations for SNPTB:

“THE CHEST RADIOGRAPH”

• “Sound clinical judgement is needed to put a

seriously ill patient with negative sputum

smear results on anti-TB treatment using

only suggestive radiographic findings

• Under such circumstances the clinical

response of the patient has to be monitored and TB diagnosis should be confirmed at

least by clinical response to anti-TB

treatment and preferably by culture.”

Key 2006 WHO Recommendations:

“DIAGNOSIS AND TREATMENT OF EPTB”

• In peripheral health facilities of HIV-prevalent

settings, health care workers should initiate empiric TB treatment early in patients with

serious illness thought to be due to EPTB

• After empiric TB treatment has been

initiated, every attempt should be made to

confirm the diagnosis of TB, including

through monitoring the clinical response of

the patient, to ensure that the patient’s

illness is being managed appropriately

• If additional diagnostic tests are unavailable,

and if referral to a higher level facility for

confirmation of the diagnosis is not possible,

TB treatment should be continued and

Key 2006 WHO Recommendations:

“DIAGNOSIS AND TREATMENT OF EPTB”

• Empiric trials of treatment with

incomplete regimens of anti-TB drugs

should not be performed.

• If a patient is treated with empiric anti-TB

drugs, treatment should be with

standardized, first-line regimens, and it

should be used for the entire duration of

TB treatment Empiric treatment should only be stopped if there is bacteriological, histological or strong clinical evidence of

an alternative diagnosis

Treatment Regimens for the PLWHA with Tuberculosis

15 mg/kg/day x 2 mo

Then INH + Eth x 6-7 months

Guidelines for the Diagnosis and Treatment of HIV/AIDS Ministry of Health,

Vietnam March, 2005 Quy HT et al 2006

*Often HIV+ patients are given Ethambutol instead of SM in the

first 2 months This is because of high rates of SM resistance in new patients (29%) and, to avoid the need for injections

Tuberculosis: National Re-Treatment Protocol

2 SHRZE / 1 HRZE / 5 H3R3E3

Month 4 – 9:

Isoniazid (H3)Rifampin (R3) Ethambutol (E3)

TB/HIV Treatment Guidelines-2000

Vietnam Ministry of Health

• Direct observation by MD in initial 2

Some recent data suggesting superiority

of HR for continuation phase

• First randomized controlled trial to compare

HR (x4 mos) vs HE (x 6mos) in continuation phase.

• 1355 patients randomized to HRZE x 2

months followed by either HE (x 6 months)

or HR (x4 mos)

• 12 months after completion of therapy

patients who had received HE were 2.86

times more likely to relapse.

• Of 68 patients co-infected with HIV 1 patient

in HR group had unfavourable outcome vs

13 in the HE group (P=.08)

Tuberculosis meningitis and

Dexamethasone

• Randomized, double-blind,

placebo-controlled study of adjunctive

• Dex did not prevent severe disability

• Fewer adverse events in dex group, esp

hepatitis

Thwaites G et al N Eng J Med 2004;351:1741-51 Slide courtesy of Dr Estee Torok

Dexamethasone Sodium Phosphate Dosing

Given as soon as possible after the start of anti-TB therapy!

Glasgow Coma Scale 1 - Alert and oriented without focal neurological deficit

• 0.3 mg/kg/day IV for week 1

• 0.2 mg/kg/day IV for week 2

• 0.1 mg/kg/day ORALLY for week 3

• 3 mg per day ORALLY for week 4 – 6, decreasing by 1 mg each week

Glasgow Coma Scale 2 or 3 - Confused to coma +/- focal

deficits

• 0.4 mg/kg/day IV for week 1

• 0.3 mg/kg/day IV for week 2

• 0.2 mg/kg/day IV for week 3

• 0.1 mg/kg/day IV for week 4

• 4 mg/day ORALLY for weeks 5-8, decreasing by 1 mg every week

Survival in 545 patients receiving adjunctive

Dexamethasone for TB meningitis

300 200

100 0

Dexamethasone

PlaceboPlacebo

Relative risk of death, 0.69 95% CI 0.52-0.92, p=0.011

Thwaites G et al N Eng J Med 2004;351:1741-51.

Slide courtesy of Dr Estee Torok

100 0

Tuberculosis Resistance

• Results from spontaneous

mutations of MTB exposed to drugs

• inadequate treatment regimens

• interrupted availability to drug

treatment

• poor quality of drug treatment

• incomplete treatment adherence

• HIV? - concerns of increased drug

resistance but conflicting data

Quy HT, Buu TN et al Int J Tuberc Lung Dis 2006;10(2):160-166.

Tuberculosis Resistance in Ho Chi Minh City

37% new and 66% previously treated TB

patients were infected with strains resistant

to any first-line TB drug

Key Points

• TB co-infection is common in PLWHA in Vietnam

Rates up to 25% have been seen in TB patients

in Ho Chi Minh City

• HIV infection dramatically increases risk for

active TB infection by over 100 fold.

• The clinical presentation of TB varies by CD4

count The lower the CD4 count, the more likely the patient will present with extrapulmonary TB and negative sputums for AFB.

• 50% of HIV patients in HCMC initially diagnosed

with AIDS Wasting Syndrome, grew MTB in

cultures from sputum and/or blood

Key Points

• TB treatment regimens for the HIV + patient who is

not on ART do not differ from the HIV negative

patient

• Adjunctive Dexamethasone in TB meningitis has been

proven to increase survival up to 9 months by 30% This was not seen in HIV + patients but larger studies are needed to demonstrate efficacy

• Mortality rates from TB meningitis in HIV+ patients

are 3 fold higher then HIV – patients

• TB resistance can be increased by inadequate and/or

poor quality treatment regimens, interrupted drug

treatment due to availability and/or adherence HIV

is not a confirmed risk factor for TB resistance

Thank you!

Questions?