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Effect of Pregnancy on Interferon Gamma Release Assay and Tuberculin Skin Test Detection of Latent TB Infection Among HIV-Infected Women in a High Burden Setting

LaCourse, Sylvia M. MD, MPH*; Cranmer, Lisa M. MD, MPH; Matemo, Daniel MPH; Kinuthia, John MBChB, MMed, MPH§,‖; Richardson, Barbra A. PhD‖,¶; Horne, David J. MD, MPH‖,#,**; John-Stewart, Grace MD, PhD*,‖,††,‡‡

JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1st, 2017 - Volume 75 - Issue 1 - p 128–136
doi: 10.1097/QAI.0000000000001298
Translational Research

Background: Peripartum immunologic changes may affect latent tuberculosis infection (LTBI) diagnostic performance among HIV-infected women.

Methods: HIV-infected women were serially tested with tuberculin skin test (TST) and interferon gamma release assay [QuantiFERON TB Gold In-tube (QFT)] in pregnancy and 6 weeks postpartum in Kenya. Prevalence, sensitivity and agreement, and correlates of QFT/TST positivity were assessed. Quantitative QFT mitogen and Mycobacterium tuberculosis antigen (Mtb-Ag) responses were compared by peripartum stage. Incidence of test conversion at 6 weeks postpartum was evaluated in baseline TST−/QFT− women.

Results: Among 100 HIV-infected women, median age was 26 years, median CD4 was 555 cells per cubic millimeter, and 88% were on antiretrovirals. More women were QFT+ than TST+ in both pregnancy (35.4% vs. 13.5%, P = 0.001) and postpartum (29.6% vs. 14.8%, P < 0.001). Among 18 consistently QFT+ women, 8 (44%) converted from TST− to TST+, with improved test agreement postpartum (56.9%, κ = 0.20 to 82.4%, κ = 0.60). Three initially QFT−/TST− women had test conversion (TST+ and/or QFT+), suggesting new infection (incidence 13.4/100 person-years). Mean QFT mitogen (4.46 vs. 7.64 IU/mL, P < 0.001) and Mtb-Ag (1.03 vs. 1.54 IU/mL, P = 0.03) responses were lower among all women retested in pregnancy vs. postpartum, and specifically among persistently QFT+ women (Mtb-Ag: 3.46 vs. 4.48 IU/mL, P = 0.007). QFT indeterminate rate was higher in pregnancy (16%) compared with postpartum (0%) because of lower mitogen response.

Conclusions: QFT identified >2-fold more women with LTBI compared with TST in pregnancy and postpartum. Lower QFT Mtb-Ag and mitogen responses in pregnancy compared with postpartum suggest that pregnancy-associated immunologic changes may influence LTBI test performance.

Supplemental Digital Content is Available in the Text.

*Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA;

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA;

Departments of Research and Programs;

§Reproductive Health, Kenyatta National Hospital, Nairobi, Kenya;

Departments of Global Health;

Biostatistics, University of Washington, Seattle, WA;

#Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington Harborview Medical Center, Seattle, WA;

**Firland Northwest TB Center, Seattle, WA; and

Departments of ††Pediatrics;

‡‡Epidemiology, University of Washington, Seattle, WA.

Correspondence to: Sylvia M. LaCourse, MD, MPH, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, 325 9th Avenue, Box 359931, Seattle, WA 98104 (e-mail:

Supported by the National Institute of Allergy and Infectious Diseases and the National Institute of Child Health and Human Development at the National Institutes of Health (K23 AI 120793-01 and T32 AI07140 to S.M.L., K23 AI 85036-01 to D.J.H., K24 HD054314-06 to G.J.-S., K12 HD000850 to L.M.C.), University of Washington Center for AIDS Research (CFAR) P30AI027757 to S.M.L., UW INTERSECT-Ellison Fellowship to S.M.L., the National Center for Research Resources at the National Institutes of Health (UL1TR000423) and the Firland Foundation.

Preliminary study results were presented at the 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19–22, 2015, Vancouver, BC, Canada; 46th International Union Against Tuberculosis and Lung Disease World Conference, December 2–6, 2015, Cape Town, South Africa; 21st International AIDS Conference, July 18–22, 2016, Durban, South Africa; and 47th International Union Against Tuberculosis and Lung Disease World Conference, October 26–29, 2016, Liverpool, United Kingdom.

The authors have no conflicts of interest to disclose.

S.M.L. and G.J.-S. designed the study and analyses. S.M.L., L.M.C., D.J.H., J.K., and D.M. conducted the study. S.M.L. and B.A.R. conducted statistical analysis. All co-authors contributed to manuscript writing.

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Received October 04, 2016

Accepted January 17, 2017

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