Madison Clinic
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Latent TB Testing at Madison Clinic

Opportunistic infection prevention guidelines recommend testing for latent TB infection (LTBI) in all HIV-infected persons at initial presentation, regardless of identifiable risk factors.1 For patients with ongoing risk factors, such as incarceration, active drug use, homelessness, annual testing for LTBI should be performed. Additionally, patients with CD4 counts < 200 cells/uL at initial presentation who tested negative and who did not receive LTBI treatment should be retested once they are on ARVs and their CD4+ counts have increased to > 200 cells/uL.

Last year, of the 303 new patients seen in our clinic, only 170 received a PPD and 52 (30%) did not return to have PPD read. 111 patients had negative PPD’s and 7 were positive.

Within the past year, the interferon gamma release assay (QuantiFERONÒ-TB Gold) became available at Harborview for latent TB testing. IGRAs are performed on whole blood incubated with synthetic peptides that represent two unique MTB proteins (ESAT-6 and CFP-10). IGRAs are more specific for TB than PPDs, as they are not positive after vaccination with BCG. Sensitivity of IGRA compared to PPD is not known as longitudinal studies to evaluate for progression to active TB are necessary to address this issue.

Studies have found variable concordance between PPD and IGRAs (kappa = 0.23-0.37) in HIV-infected individuals2-5  Lower CD4 counts are more likely to yield indeterminate results. Indeterminate IGRA results are generally due to lack of response to positive controls. In one study of 294 HIV+ patients performed in a population similar to that of the Madison Clinic, only 8/29 (28%) of patients had a positive test results by both PPD and IGRA.4  Five percent of patients had either a positive PPD/negative IGRA or negative PPD/positive IGRA. None of the patients with CD4 counts < 100 cell/mm3 in this study had a positive result by either test.

If either IGRA or PPD is positive, then patients should undergo further evaluation including chest Xray to rule out active TB.  Patients with indeterminate IGRA results may have repeat IGRA performed or have PPD placed instead. In one study in mostly HIV-negative individuals, 16% of patients initially indeterminate by IGRA, had determinate results on repeat testing.6

Given our poor return rate for PPD reading, IGRA should be considered for all new patients to rule out LTBI. Providers should also consider ordering PPDs as well given the variable concordance found in previous studies and the relative lack of data for IGRAs in the HIV-infected population. For patients with ongoing risk, PPD and/or IGRA should be performed annually.

IGRAs are run once a week on either Thursdays or Fridays at UW Virology at Children’s and results available the same day the test is run. Specimens must be in the lab by 2pm to perform test. Specimens obtained after 2pm cannot be run. Due to these laboratory constraints, afternoon patients may have a PPD placed that same day and/or can take prepared lab requisitions and have IGRA drawn (and other labs) before their next clinic visit or on a morning convenient for them.

Summary of changes to clinic protocol:

  • PPD and IGRA for all newly diagnosed patients or new to clinic patients without previous LTBI testing
  • PPD and/or IGRA annually for patients with ongoing risk factors for TB infection
  • PPD and/or IGRA for patients who initially tested negative with low CD4 counts who are now on ARVs with CD4 counts > 200 cells/mm3

For nursing:

Collection: Use Quantiferon TB blood tubes and collect 1 mL blood in each tube:  [one NIL (Grey cap), one TB Ag (Red cap), one MIT (Lavender cap) ].
The black mark on the side of tubes indicates the 1 mL fill volume.  Do not under or over-fill. Mix all three tubes by vigorously shaking the tubes for 5 seconds (or 10 times) to ensure that the entire inner surface of the tube has been coated with the blood. Foaming of the blood is expected.

Handling: Specimen must be incubated within 16 hours.  Specimen must arrive at Virology lab within 10-12 hours of draw.

Note:  Quantiferon TB collections tubes are available in Lab Medicine's Specimen Processing, call 598-6224.  Store blood collection tubes at 4°C to 25°C
Amount:       1 mL blood/each tube
Minimum:      1 mL blood/each tube


1.  Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009;58:1-207; quiz CE1-4.
2.  Talati NJ, Seybold U, Humphrey B, et al. Poor concordance between interferon-gamma release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals. BMC Infect Dis 2009;9:15.
3.  Karam F, Mbow F, Fletcher H, et al. Sensitivity of IFN-gamma release assay to detect latent tuberculosis infection is retained in HIV-infected patients but dependent on HIV/AIDS progression. PLoS One 2008;3:e1441.
4.  Luetkemeyer AF, Charlebois ED, Flores LL, et al. Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals. Am J Respir Crit Care Med 2007;175:737-42.
5.  Stephan C, Wolf T, Goetsch U, et al. Comparing QuantiFERON-tuberculosis gold, T-SPOT tuberculosis and tuberculin skin test in HIV-infected individuals from a low prevalence tuberculosis country. AIDS 2008;22:2471-9.
6.  Kobashi Y, Sugiu T, Mouri K, Obase Y, Miyashita N, Oka M. Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice. Eur Respir J 2009;33:812-5.


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