Diminished <i>Mycobacterium tuberculosis</i>-specific T-cell Responses During Pregnancy in Women With HIV and Receiving Isoniazid Preventive Therapy

Background Pregnancy increases Mycobacterium tuberculosis (Mtb) reactivation risk and alters immune responses. We assessed Mtb-specific CD4+ T-cell responses in pregnant women with HIV (WLHIV) and without, including those receiving isoniazid preventive therapy (IPT). Methods We measured adaptive immune responses from 33 participants (HIV+ 21, HIV- 12) with positive interferon-gamma release assay during pregnancy (20-34 weeks' gestation), 6 weeks, and 12 months postpartum by intracellular cytokine staining. We measured overall responses using COMPASS and made comparisons by nonparametric analysis of variance. Result We observed diminished Mtb-specific CD4+ T-cell responses in WLHIV during pregnancy versus 12 months postpartum (COMPASS median functional score [FS] .009 vs 0.12, P = .03). WLHIV who received IPT (n = 8) during concurrent pregnancy had attenuated Mtb-specific CD4+ T-cell responses during pregnancy versus 12 months postpartum (median FS 8.3 × 10 -7 vs 0.13, P = .02), but WLHIV who did not receive IPT during pregnancy had similar responses in pregnancy and postpartum. Mtb-specific CD8+ FS was increased postpartum in all groups. We found preexisting Mtb-specific CD4+ T-cell responses in participants who converted interferon-gamma release assay tests postpartum (n = 10). Conclusions Pregnant WLHIV, especially those on IPT, showed reduced Mtb-specific CD4+ T-cell responses. Understanding the impact of pregnancy on Mtb-specific T-cell responses may improve diagnostic approaches.