Zika virus infection during pregnancy and vertical transmission: case reports and peptide-specific cell-mediated immune responses.

Zika virus (ZIKV) infection in pregnant women is associated with birth defects, which are more prevalent and severe the earlier in pregnancy the infection occurs. Pregnant women at risk of possible ZIKV exposure (n = 154) were screened using ELISA for ZIKV IgM and IgG. Nine of 154 (5.84%) pregnant women who underwent screening exhibited positive ZIKV serology. Of these, two maternal infections were confirmed by real-time RT-PCR and five were considered probable, but only three of those were retained for further analysis based on strict diagnostic criteria. Plaque reduction neutralization tests (PRNT) confirmed ZIKV infection in nine cases (5.84%). Two cases of vertical ZIKV transmission were confirmed by PCR. One infant showed no signs of congenital ZIKV syndrome and had a normal developmental profile despite first-trimester maternal infection. In the second case, pregnancy was terminated. Production of interferon γ (IFN-γ) by peripheral blood mononuclear cells obtained from pregnant women and umbilical cord blood was measured using enzyme-linked immunospot assay (ELISpot) after stimulation with panels of synthetic peptides derived from the sequence of ZIKV proteins. This analysis revealed that, among all peptide pools tested, those derived from the ZIKV envelope protein generated the strongest IFN-γ response.

Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen.

Introduction: The use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm delivery. As this outcome may be related to systemic inflammation, we sought to characterize inflammatory profiles of pregnant people living with HIV (PLWH) by comparing their levels of inflammatory mediators at two timepoints during pregnancy according to ART regimen, and to HIV-negative controls. Methods: Second and third trimester samples from 144 pregnant PLWH treated with ART and 24 HIV-uninfected controls were retrieved from the CARMA-PREG cohort. Peripheral plasma levels of 12 inflammatory mediators previously linked to HIV infection and/or poor pregnancy outcomes were quantified by multiplex assay: HMGB1, GM-CSF, IFNα, IFNß, IFNγ, IL-10, IL-17, IL-1ß, IL-6, TNFα, AGP, and CRP. Levels were compared by ART regimen and HIV status. Results: Adjusted analyses showed that PLWH have higher levels of AGP throughout pregnancy and lower levels of IFNγ and IL-1ß during the second trimester. PI-based regimens are associated with significantly higher levels of IFNα and IL-17 during the second trimester and IFNα, CRP, HMGB1, and IFNß during the third trimester compared to InSTI-based regimens. The PI-subgroup was associated with preterm delivery and higher HIV-1 viral load. Discussion: Our results suggest that PI-based regimens are associated with a pro-inflammatory and antiviral immunological response and a high viral load, which may be a mechanism through which PI-based regimens increase the risk of preterm delivery. Further investigations into cellular mechanisms and pro-inflammatory cascades leading to preterm delivery are necessary to support this association.

Placenta analysis of Hofbauer cell profile according to the class of antiretroviral therapy used during pregnancy in people living with HIV.

INTRODUCTION: The use of antiretroviral therapy drastically reduces vertical transmission of Human Immunodeficiency Virus. However, recent studies demonstrate associations between ART use during pregnancy and placental inflammation, particularly within protease inhibitor (PI)-based regimens. We sought to characterize placental macrophages, namely Hofbauer cells, according to the class of ART used during pregnancy. METHODS: Using immunofluorescence and immunohistochemistry, placentas from 79 pregnant people living with HIV (PPLWH) and 29 HIV-uninfected people were analyzed to quantify the numbers and frequencies of leukocytes (CD45+) and Hofbauer cells (CD68+ and/or CD163+). PPLWH were stratified into three groups based on class of ART: non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, integrase strand-transfer inhibitor (INSTI)-based, and PI-based regimens. RESULTS: Placentas of PPLWH contained significantly more leukocytes and Hofbauer cells than controls. Multivariable analyses revealed that this increase in immune cells was associated with a predominantly CD163+ profile in all ART subgroups compared to the HIV-negative group. This was characterized by an increase in total CD163+ cells in the PI and INSTI subgroups, and a higher frequency of CD163+ cells and CD163+/CD68+ ratio in the NNRTI and PI subgroups. DISCUSSION: Placentas of PPLWH treated with any ART regimen during their entire pregnancy displayed a selection for CD163+ cells compared to the HIV-negative group, regardless of class of ART, suggesting that class of ART does not intrinsically affect selection of CD163+ and CD68+ Hofbauer cells. Further investigations into the role of Hofbauer cells in ART-associated placental inflammation are warranted to identify the mechanisms behind their potential involvement in maternal-fetal tolerance maintenance.