Effects of Pregnancy and Isoniazid Preventive Therapy on Mycobacterium tuberculosis Interferon Gamma Response Assays in Women With HIV

Adriana Weinberg; Lisa Aaron; Grace Montepiedra; Timothy R Sterling; Renee Browning; Blandina Mmbaga; Tichaona Vhembo; Shilpa Naik; Enid Kabugho; Gaerolwe Masheto; Savita Pahwa; Jyoti S Mathad; Sylvia M LaCourse; Katie McCarthy; Sarah Bradford; Gerhard Theron; Diane Costello; Bonnie Zimmer; Marie F Pierre; Kamunkhwala Gausi; Paolo Denti; David W Haas; Amita Gupta; IMPAACT P1078 study team

doi:10.1093/cid/ciaa1083

Effects of Pregnancy and Isoniazid Preventive Therapy on Mycobacterium tuberculosis Interferon Gamma Response Assays in Women With HIV

Clin Infect Dis. 2021 Nov 2;73(9):e3555-e3562. doi: 10.1093/cid/ciaa1083.

Authors

Adriana Weinberg¹, Lisa Aaron², Grace Montepiedra², Timothy R Sterling³, Renee Browning⁴, Blandina Mmbaga⁵, Tichaona Vhembo⁶, Shilpa Naik⁷, Enid Kabugho⁸, Gaerolwe Masheto⁹, Savita Pahwa¹⁰, Jyoti S Mathad¹¹, Sylvia M LaCourse¹², Katie McCarthy¹³, Sarah Bradford¹³, Gerhard Theron¹⁴, Diane Costello¹⁵, Bonnie Zimmer¹⁶, Marie F Pierre¹⁷, Kamunkhwala Gausi¹⁸, Paolo Denti¹⁸, David W Haas³, Amita Gupta¹⁹; IMPAACT P1078 study team

Collaborators

IMPAACT P1078 study team:
Alisa Shao, Mandisa Nyati, Jeanne Louw, Tebogo J Kakhu, Tsungai Chipato, Lynda Stranix-Chibanda, Nishi Suryavanshi, Fuanglada Tongprasert, Celeste de Vaal

Affiliations

¹ Department of Pediatrics, Medicine and Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
² Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
³ Vanderbilt Tuberculosis Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁴ Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁵ Kilimanjaro Christian Medical Centre (KCMC) Moshi, Tanzania.
⁶ University of Zimbabwe College of Health Sciences Clinical Trials Research Centre (UZCHS-CTRC), Harare, Zimbabwe.
⁷ Department of Obstetrics and Gynaecology, BJGMC, Pune, India.
⁸ Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
⁹ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana, and Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁰ Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.
¹¹ Department of Medicine, Center for Global Health, Weill Cornell Medicine, New York, New York, USA.
¹² Department of Medicine, University of Washington, Seattle, Washington, USA.
¹³ FHI 360, Durham, North Carolina, USA.
¹⁴ FAM-CRU CRS, Department of Obstetrics and Gynaecology, Stellenbosch University, Cape Town, South Africa.
¹⁵ University of California Los Angeles, Los Angeles, California, USA.
¹⁶ Frontier Science Foundation, Amherst, New York, USA.
¹⁷ Les Centres GHESKIO, Port-au-Prince, Haïti.
¹⁸ Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
¹⁹ Departments of Medicine and International Health, Johns Hopkins University, Baltimore, Maryland, USA.

Abstract

Background: Pregnancy is accompanied by immune suppression. We hypothesized that Mycobacterium tuberculosis-specific inflammatory responses used to identify latent tuberculosis infection (LTBI) lose positivity during pregnancy. We also hypothesized that isoniazid preventive therapy (IPT) may revert LTBI diagnoses because of its sterilizing activity.

Methods: 944 women with human immunodeficiency virus infection (HIV) participating in a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT antepartum versus postpartum, were tested by QuantiFERON-gold-in-tube (QGIT) antepartum and by QGIT and tuberculin skin test (TST) at delivery and postpartum. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations.

Results: From entry to delivery, 68 (24%) of 284 QGIT-positive women reverted to QGIT-negative or indeterminate. Of these, 42 (62%) recovered QGIT positivity postpartum. The loss of QGIT positivity during pregnancy was explained by decreased interferon gamma (IFNγ) production in response to TB antigen and/or mitogen. At delivery, LTBI was identified by QGIT in 205 women and by TST in 113 women. Corresponding numbers postpartum were 229 and 122 women. QGIT and TST kappa agreement coefficients were 0.4 and 0.5, respectively. Among QGIT-positive women antepartum or at delivery, 34 (12%) reverted to QGIT-negative after IPT. There were no differences between women who initiated IPT antepartum or postpartum.

Conclusions: Decreased IFNγ responses in pregnancy reduced QGIT positivity, suggesting that this test cannot reliably rule out LTBI during pregnancy. TST was less affected by pregnancy, but had lower positivity compared to QGIT at all time points. IPT was associated with loss of QGIT positivity, the potential clinical consequences of which need to be investigated.

Keywords: HIV infection; interferon gamma response assays; isoniazid preventive therapy; latent tuberculosis infection; pregnancy.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Female
HIV Infections*
Humans
Interferon-gamma
Interferon-gamma Release Tests
Isoniazid / therapeutic use
Latent Tuberculosis* / diagnosis
Latent Tuberculosis* / drug therapy
Mycobacterium tuberculosis*
Pregnancy
Tuberculin Test

Substances

Interferon-gamma
Isoniazid

Abstract

Publication types

MeSH terms

Substances

Grants and funding