1387. Women Living with HIV (WLWH) Lose IFNγ Responses Diagnostic of Latent TB Infection (LTBI) during Pregnancy and after INH Prophylactic Treatment (IPT)

Abstract

BackgroundTB is the most common opportunistic infection in PLWH. IPT is recommended for PLWH in endemic areas and for those with LTBI diagnosed by Quantiferon gold-in-tube (QGIT) or tuberculin skin test (TST) in other areas. We report on the performance of QGIT and TST in pregnant WLWH who received IPT antepartum (AP) or postpartum (PP).MethodsWLWH participating in IMPAACT P1078, a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT AP vs. PP, were tested by QGIT at entry (14–34 weeks gestation) and by QGIT and TST at delivery (L&D) and 44 weeks PP. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations.ResultsAmong 944 women with study entry mean (SD) of 29 (6) years of age, 521 (245) CD4+ cells/µL, on ART, including 63% with undetectable HIV plasma RNA, 284/944 (30%) were QGIT+ AP, 215/862 (25%) at L&D and 246/764 (32%) PP (P < 0.001), while 127 (15%) were TST+ at L&D and 126 (17%) PP. QGIT was more likely positive than TST at L&D (Odds ratio = 4.3; 95% CI = 2.8–6.8) and PP (6.4; 3.9–10.7; P < 0.001). QGIT and TST agreement coefficients (95% CI) were 0.4 (0.3–0.5) at L&D and 0.5 (0.4–0.5) PP. Among women QGIT+ AP, 59 (24%) reverted to QGIT- or indeterminate at L&D. However, 37 (63%) reverters recovered QGIT+ results PP, suggesting transient suppression of IFNg responses during pregnancy. Responses to the mitogen-positive QGIT kit control were absent in 60 (7%) women AP, 116 (16%) at L&D, but only 3 (0.4%) PP (P < 0.01), supporting the notion of transient immune suppression during pregnancy. Among women QGIT- AP, 33 (7%) converted to QGIT+ PP. Among AP QGIT+ women, 24 (11%) reverted to QGIT- PP after finishing IPT. None of the results differed between treatment arms (P ≥ 0.13).ConclusionIn WLWH on ART, the loss of IFNγ responses to TB antigen and mitogen in pregnancy decreased the diagnostic value of QGIT. TST was similar at L&D and PP but was less sensitive than QGIT. QGIT conversions likely resulted from a combination of PP immune reconstitution and new TB infections. QGIT reversions might represent a change in TB-specific immunity in response to IPT. Reversions have been reported in adults without HIV after treatment of active TB. The clinical significance of QGIT reversions in PLWH needs further investigation.Disclosures All authors: No reported disclosures.