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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?