Defining Appropriate Comparator Populations for Placental Pathology for Pregnant People With HIV

Background. Widespread adoption of antiretroviral therapy has reduced perinatal transmission of HIV; however, people living with HIV (PWH) have higher rates of preterm birth and hypertensive disorders of pregnancy. The placenta is the critical fetal support organ in pregnancy, and multiple investigations have sought associations in PWH between HIV and placental pathology. However, results have been inconclusive. We posit that selection of control group populations influences the apparent anomalies in placentas from PWH and examined the differences seen between these placentas and those of four comparator populations. Methods. Placentas from PWH were compared with those from all patients without HIV, controls from a recent study of severe acute respiratory syndrome coronavirus 2 in pregnancy, patients with a history of melanoma-an indication for examination relatively orthogonal to other problems in pregnancy, and patients paired with PWH using propensity score matching. Results. People living with HIV differ in demographics and comorbidities from comparator groups other than propensity score-matched patients. Placentas from PWH had higher rates of acute placental inflammation, including maternal inflammatory response and fetal inflammatory response, than multiple comparator groups. Placentas from PHW had lower rates of chronic placental inflammation than three of four comparator groups, including the largest comparator group and the group matched to PWH using propensity scores. Conclusion. Differences in placental pathology in PWH depend on the comparator group. Commonly used comparator groups have significantly different demographic and comorbidity profiles, suggesting they are inappropriate comparators for PWH. Propensity score matching may be useful in identifying comparator populations.