HIV and TB

Jeffrey D. Klausner, MD, MPHProfessor of Medicine and Public Health

Program in Global Health, Division of Infectious Diseases David Geffen School of MedicineFielding School of Public Health

Special thanks to: Caitlin Reed MD, MPHMedical Director, Inpatient TB Unit, Olive View – UCLA Medical Center

Los Angeles County Department of Health Services

September 2014African-American HIV University

Disclosures

• Dr. Klausner is a faculty member of the University of California Los Angeles

• Dr. Klausner is a guest researcher with the US CDC Mycotics Diseases Branch

• Dr. Klausner is a member of the WHO STD Guidelines group

• Dr. Klausner is a board member of YTH, Inc, non-profit

• Dr. Klausner is medical advisor for Healthvana.com

• In the past 12 months, Dr. Klausner has received:

– Travel support for meeting coordination and speaking from Standard Diagnostics, Inc.

– Research funding or donated supplies from the NIH, CDC, Hologic, Inc., Alere, Inc., Chembio, Inc. Cepheid, Standard Diagnostics, Inc., and MedMira, Inc.

JDKlausner@mednet.ucla.edu

Objectives: TB Update

1) Review of TB epidemiology & pathogenesis

2) New tests and treatment for latent TB

3) Diagnosis of active TB

4) TB puzzles

TB Frequency

Reported TB Cases, U.S. 1982-2012

CDC MMWR 2010

Where is TB?

Global Tuberculosis Control 2011; WHO

TB is Not Gone

• 1/3 of the world’s population is infected with TB (Latent TB infection)

• Globally 9 million new cases of active TB / year

• 1.3 million TB deaths / year

Tuberculosis Cases in Foreign-born and U.S.-born Persons by Race/Ethnicity: California, 2010

Credit: CDPH TB Control Program

Natural History of TB

Exposure

Close Aerosol ContactWith an Infectious Case

Infection

Latent Infection • Asymptomatic• Not Infectious

Active TB disease

10% lifetime risk 5% first 2 years after infection•

90%

10%

Treat latent TB to prevent active TB

X

Relative Risk for Developing Active TB

by Risk FactorsRisk Factor Approximate RiskHIV/AIDS 170 *

Lung Disease due to Silica 30

Immunosuppression 10-15

Cancer 10-15

Hemophilia 5-10

Kidney failure 10-15

Malnutrition 2-4

Diabetes 2-4

Smoking 2

Targeted Tuberculin Testing and Treatment of Latent TB InfectionCDC, MMWR June 2000

Why do HIV-infected patients get TB? *

1) Immune suppression leads to activation of old TB

2) Re-exposure in clinics and hospitals leads to new infection

Latent TB Infection

Targeted TB screening

1) People at increased risk of recent infection• Close contacts of active TB case• Recent immigrants from countries with TB• Work exposure

– Nursing home, hospital, jail/prison

2) Risk factors for active TB• Pts with HIV infection• Other immunosuppressed persons

TB Screening Tests

• Tuberculin skin test (TST) • Interferon-gamma release assays (IGRAs)

– Quantiferon-Gold In-Tube (Cellestis)– T. Spot TB (Oxford Immunotect)

• Quantiferon is the most commonly use TB screening test in patients with HIV-infection *

TB Skin Test

48-72 hrs

• Interpretation depends on risk factors • Reader error• No immune response in some pts• Reactivity

Quantiferon TB Testing

• Measures immune response to TB antigens• Similar principle to TST

– Uses TB-specific antigens – Not affected by BCG vaccination (specific)

TST and Quantiferon

Antigenpresenting

cell

MemoryT-cell

Presentation ofmycobacterial antigens

IFN-

IFN-

IL-8, etc.

IL-8, etc.

TNF-

TNF-

Andersen P, et al. Lancet 2000;356:1099

Tuberculin skin test

IGRA

Case 1

• 32 year old health care worker with positive Quantiferon Test

• Denies cough, fever, weight loss, night sweats• Chest x-ray negative• Treat for latent TB infection

– 9 months isoniazid daily or– 4 months rifampin daily or– 3 months of isoniazid/ rifapentine weekly

Treatment of latent TB in patients with HIV infection

• 6 months of isoniazid

• Some recommend 36 months

• ? Perhaps until CD4 > 500

Active TB

ExposureLatent TB Infection

Active TB Infection Symptomatic

Death

Treatment

TB Diagnostic Tests

• Smear microscopy (sputum, tissue)

• Mycobacterial Culture (sputum, blood, tissue)

• Nucleic Acid Amplification Tests (sputum, tissue)

Sputum Smear Microscopy

• Easy, rapid, cheap

– Sensitivity*:

• In field conditions : 40-60%

• HIV- infected patients: 20-60%

– Specificity: Not specific for M. tuberculosis

Arrow: Acid Fast Bacilli

*WHO Stop TB Diagnostics Working Group Strategic Plan 2006-2015

Mycobacterial Culture

• Reference Standard for diagnosis of TB

• Can send from any body site• Solid or liquid culture medium

• Limitation:– Slow (mean: 24 days for positives)– Resource intensive, costly

Drug Susceptibility Culture Testing

• Diagnosis of drug-resistant TB• Conventional Methods:

– Grow TB in culture – Assess for growth (resistant)

or absence of growth (susceptible)

at 4 weeks

Nucleic Acid Amplification Tests

– Amplify nucleic acid segments specific for M. tuberculosis

– Rapid: Results in 24-48 hours

– Commercially Available:• Mycobacterium Tuberculosis Direct

(MTD)• Amplicor M.Tb Test (Amplicor)• Cepheid GeneXpert MTB Rif

Cepheid GeneXpert MTB Rif

Case 2

• 66 yo homeless man with abnormal chest xray, weight loss, chronic cough

• Smear positive for AFB• HIV-infected• Treatment?

– 4 drug regimen: Rifampin, INH, PZA, Ethambutol– May stop PZA after 2 months– May stop Ethambutol if no resistance – For 6 to 9 months total duration

TB and HIV infection

• Difficult to diagnosis (low amount of TB)• Drug-drug interactions• Immune reconstitution inflammatory syndrome (IRIS)

– Delay antiretroviral therapy until on TB treatment• If CD4 < 50 delay 2 weeks• If CD4 > 50 and stable, delay 8 weeks

– Monitor for worsening– Consider addition of steroids

New developments in TB

• Ongoing search for point of care test– Urine LAM: antigen detection; potentially

useful, in HIV-infected patients with CD4 <50

• Reports of ‘Totally Drug Resistant’ TB • Finally, new drugs for drug-resistant TB

– Bedaquiline (Sirturo)– FDA approved Dec 2012 for MDR-TB

– Delaminid – phase III trial

Olive View Inpatient TB Unit

TB Unit15 beds (10 staffed currently)Patients must be stable with lab-confirmed TB

Categories of patients• Infectious, need prolonged isolation• Drug resistant TB requiring special management• TB drug adverse reactions• Public health detention

Group questions & dilemmas

Group 1

The patient has HIV infection but his TB skin test is negative

What are 3 possible explanations?

Group 2

A patient has been started on TB medicines. He initially gets better and then gets worse.

What are 3 possible explanations?

Group 3

• Name 3 groups that are high risk for TB

• Describe 3 ways the risk for TB might be decreased in those groups?

Group 4

• TB is a public health condition that gets reported to the health department.

• Name 3 other “reportable” conditions

• Describe what the health department does with that information

Thank you