Effects of Pregnancy and Isoniazid Preventive Therapy on M. tuberculosis Interferon Gamma Response Assays in Women with HIV

Post Date: 
Clinical Infectious Diseases

Background: Pregnancy is accompanied by immune suppression. We hypothesized that M. 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 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 (24%) 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 IFNγ production in response to TB antigen and/or mitogen. At delivery, QGIT identified 205 and TST 113 women with LTBI. 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.

Weinberg A, Aaron L, Montepiedra G, Sterling TR, Browning R, Mmbaga B, Vhembo T, Naik S, Kabugho E, Masheto G, Pahwa S, Mathad JS, LaCourse SM, McCarthy K, Bradford S, Theron G, Costello D, Zimmer B, Pierre MF, Gausi K, Denti P, Haas DW, Gupta A; IMPAACT P1078 study team. 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. PMID: 32720695; PMCID: PMC8563205.