The mechanisms behind the link between HIV infection or antiretroviral therapy (ART) and the risk of preterm delivery (PTD) and small-for-gestational-age (SGA) during pregnancy are unknown. The researchers determined the link between cellular immune activation and PTD or SGA in HIV-positive women who started ART during or before pregnancy. Women with HIV who were included at a median of 15 weeks gestation were tested for immunological markers and matched on when they started antiretroviral therapy (15 women initiated pre- and 15 during pregnancy). There were 30 PTD cases (delivery less than 37 weeks), 30 SGA cases (weight for age less than or equal to 10th percentile), and 30 controls (term, weight for gestational age greater than 25th percentile). Flow cytometry was used to count the number of lymphocytes, monocytes, and dendritic cells, as well as their activation status and functioning. When compared to SGA cases and term controls (all P<.05), PTD cases who started ART during pregnancy had lower CD8+ T cell, monocyte, and dendritic cell activation, higher classical (CD14+CD16–) and intermediate (CD14+CD16+) monocyte frequencies, and lower inflammatory monocytes (CD14dimCD16+). When baseline viral load was taken into account, the immunological indicators remained significantly linked to PTD, but only in women who started ART during pregnancy. Lower monocyte activation was linked to a higher risk of PTD. In PTD women starting ART during pregnancy, TLR ligand-induced interferon and macrophage inflammatory protein-1β levels in monocytes were considerably lower. Low immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation was linked to PTD but not SGA in women who started ART during pregnancy but not before, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women who started ART during pregnancy.
Link:academic.oup.com/cid/article/73/12/2205/6144975
