Background: Maternal HIV infection increases the risk of congenital CMV infection (cCMV) >4-fold compared to the general population, even with effective ART during pregnancy. It is unknown what proportion of these cCMV cases are due to reactivation of chronic CMV infection versus maternal reinfection with a new CMV strain during pregnancy.


Methods: Samples were drawn from a prospective cohort (1999-2020) of pregnant CMV+ women living with HIV (WLWH) and their newborns exposed to but not infected with HIV. Serologic testing of maternal plasma from the first (T1) and third trimester (T3) was performed using standard clinical tests and a strain-specific ELISA that distinguishes between antibody responses directed against 4 different circulating CMV variants. Reinfection was defined by acquisition of an antibody response to a new epitope between trimesters of pregnancy. cCMV status was confirmed via qPCR on infant serum, plasma, or urine within 21 days of life.


Results: Among 411 pregnancies with available samples at T1 and T3, six (1.63%) of 369 newborns were positive for cCMV. A greater IgG titer increase from T1 to T3 was observed in cCMV cases (mean difference=607 AU/mL ) compared to those without cCMV (mean difference=121 AU/mL; p<0.01). Of 299 pregnancies with type-specific serology results, 14 reinfections (4.7%) were detected, two of which were associated with cCMV. Compared to cCMV cases without reinfection, those with reinfection had significantly lower T3 IgG titers.


Conclusion: Our results suggest that most cCMV among WLWH occurred due to reactivation of latent CMV infection. However, because strain-specific ELISA does not capture responses to all circulating CMV variants, the rate of reinfection was likely underestimated. More sensitive methods for detecting CMV reinfection are needed to inform strategies to prevent cCMV among children of WLWH.

Background: Children who are HIV-exposed and uninfected (CHEU) may have an increased risk of infectious diseases due in part to immune dysregulation. Cytomegalovirus (CMV) is a highly immunomodulatory virus that predisposes to infectious diseases among transplant recipients. We therefore assessed the impact of CMV infection on lymphocyte populations among CHEU.

Methods: CHEU enrolled in the CMIS cohort (Montreal, Canada, 1997-2010) were retrospectively evaluated for CMV by PCR in serum or plasma before 3 weeks and at 2 months of life using the Altona AltostarTM assay. We classified infants as having congenital (PCR positive before 3 weeks) or postnatal (PCR positive only at 2 months) CMV infection, and as CMV-positive if either test was positive. Lymphocyte subsets were measured by flow cytometry at 2 months of age.

Results: Among 334 non-breastfed CHEU, 7 (2.1%) had congenital and 5 (1.5%) had postnatal infection by 2 months of age. Compared to CMV-negative infants, congenital and postnatal infection were associated with detectable maternal HIV viral load (>50 copies/ml) at delivery (OR 4.31, 95%CI [1.12-13.9] and 4.31, 95%CI [1.35-13.8], respectively). There were no differences according to maternal CD4 count at delivery or gestational age. While total CD3+ T-cell and CD19+ B-cell frequencies were similar between CMV-positive and CMV-negative infants, CMV-positive infants had significantly higher CD8+ T-cell frequencies (20 vs. 15%, p<0.001), lower CD4+ T-cells frequencies (35 vs. 49%, p=0.006), and lower CD4/CD8 ratios (1.84 vs. 3.26, p<0.001). These differences remained statistically significant after adjusting for gestational age, maternal CD4 count and viral load at delivery, and the type of postnatal prophylaxis.

Conclusion: Congenital CMV infection was common in this Canadian CHEU cohort. As in other populations, CMV infection was associated with decreased CD4+ and increased CD8+ frequencies. Future research is needed to determine the contribution of CMV to immune dysregulation and infectious diseases among CHEU.

BACKGROUND: Preterm births, sexually transmitted infections (STIs), and bacterial vaginosis (BV) are common in women living with HIV (WLWH). Our study aimed to identify the impact of antenatal diagnosis of STIs and BV on preterm birth in WLWH.

METHODS: We analyzed the British Columbia perinatal HIV surveillance database for births from January 1997 to December 2022. The primary outcome is deliveries < 37 weeks gestational age (preterm births). “Sexually transmitted infection or bacterial vaginosis” (STIBV) is a composite variable of Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), Trichomonas vaginalis (TV), or bacterial vaginosis (BV) diagnosis. Risk factors were identified through univariate and multivariate logistic regression analyses.

RESULTS: Out of 578 singleton pregnancies in WLWH, 111 (19.2%) delivered preterm. In our cohort, 11% were identified with STIBV in pregnancy. The preterm birth rate in WLWH with a diagnosed STIBV was 37% vs. 17% in those without (OR: 2.18; p = 0.0003). Specifically, preterm deliveries were more common in individuals with antenatal concurrent Hepatitis C (OR: 2.42; p < 0.0001), Chlamydia trachomatis (OR 2.17; p = 0.036), Trichomonas vaginalis (OR: 2.78; p < 0.001) and bacterial vaginosis (OR: 2.15; p = 0.003). After adjusting for substance use, ethnicity, viral suppression, and preterm birth history, STIBV remains an independent risk factor (RR: 1.95; 95% CI: 1.02 – 3.75; p = 0.045).

CONCLUSION: Sexually transmitted infections and bacterial vaginosis are risk factors for preterm birth in WLWH. For WLWH, comprehensive screening for sexually transmitted and bloodborne infections and bacterial vaginosis in pregnancy is crucial.

Introduction. Combination antiretroviral (ARV) therapy (ART) is imperative to improving maternal health and preventing perinatal HIV transmission. However, some ARVs have been associated with increased risk for adverse pregnancy and birth outcomes including preterm and small for gestational age births. Proper placental development is essential for the exchange of nutrients, oxygen, and waste products throughout pregnancy. Any impairments to this process may contribute to adverse outcomes. We hypothesized that exposure to specific ARV classes (protease inhibitors [PIs], non-nucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors [INSTIs]) differentially affect placental vascular development.

Methods. Term placentas from 35 Canadian individuals (13 HIV-seronegative, 22 HIV-seropositive) were included. Individuals with HIV were taking either PI- (ritonavir-boosted lopinavir or ritonavir-boosted atazanavir), NNRTI- (nevirapine), or INSTI-based (dolutegravir or raltegravir) ART. Morphological observations were conducted using histological staining (Masson's Trichrome Stain). Quantitative analysis of capillary-per-villous ratios were performed via stereological tools to assess vascular development and patterning.

Results. Histological examination of placentas exposed to NNRTI-based ART revealed an under-branched morphology characterized by a preponderance of intermediate villi and lack of terminal villi. Placentas exhibited a thick syncytium and diminutive capillary structures. Placentas exposed to INSTI-based ART displayed an over-branched and hyper-capillarized morphology accompanied by disorganized smooth muscle in the stem villous structures. In agreement with morphological observations, stereological analysis showed that NNRTI-exposed placentas exhibited a significantly lower capillary-to-villous ratio than HIV-seronegative controls (p<0.05). PI-based ART revealed no differences in capillary-to-villous ratios compared to controls.

Conclusions. Our findings highlight the divergent effects of NNRTI- and INSTI-based regimens on placental morphological features. The observed changes in capillary villous ratios underscore the potential shift toward an under-branched state induced by NNRTI exposure. Future studies with a larger sample size are merited to explore associations between ARV-induced placenta morphological changes and birth outcomes.

Background: The menstrual cycle, sometimes deemed a fifth vital sign, is a critical indicator of women’s health. Amenorrhea, the reversible lack of a menstrual period, increases risk for morbidity and mortality. Amenorrhea research in women with HIV is inconsistent, often lacks an adequate control sample, and seldom reflects the Canadian context. We aim to determine whether women with HIV have a higher lifetime prevalence of amenorrhea and whether this is independently associated with HIV and other bio-psycho-social variables.
Methods: Women sex-assigned female at birth were eligible if aged ≥16 years, not pregnant/lactating, and without anorexia/bulimia nervosa history. Amenorrhea was defined by self-reported history of no period for at least 12 months ever, not due to pregnancy/lactation, medications that affect hormones, or menopause. Univariable and multivariable logistic regression models explored bio-psycho-social covariates of amenorrhea (Table 1).
Results: Overall, 317 women with HIV and 420 similarly aged controls were included (Table 1). History of amenorrhea was significantly more prevalent among women with HIV than controls (24.0 versus 13.3%; p<0.001). In the multivariable analysis, independent covariates of amenorrhea included HIV status (adjusted odds ratio=1.70 (1.10-2.64), older age (1.01 (1.00-1.04)), white ethnicity (1.92 (1.24-3.03)), substance use history (6.41 (3.75-11.1)), and current food insecurity (2.03 (1.13-3.61)).
Conclusions: Amenorrhea is highly prevalent among women with HIV, and associated with some modifiable risk factors including substance use and food insecurity. Given that HIV status is independently associated with amenorrhea, care providers should regularly assess women’s menstrual health and advocate for actionable socio-structural change to mitigate risk.

Background: Understanding factors associated with healthy aging is a priority for women living with HIV (WLWH). Data describing associations between socio-structural factors disproportionately affecting WLWH, burden of concurrent illnesses, and polypharmacy are needed to highlight areas for improvement.

Methods: BCC3 is a community-based study of healthy aging among WLWH and controls ≥16y. We included 224 WLWH and 312 controls. Demographics and number of non-HIV prescribed medications were self-reported. The question “has a doctor ever diagnosed you with __” assessed 45 physical and 13 mental health diagnoses. Groups were compared univariately (Mann-Whitney, Fisher’s, Chi-Squared tests) and through multivariable negative binomial regression.

Results: Demographics and socio-demographic experiences are reported in Table 1. In multivariable analyses (adjusted for demographics in Table 1), WLWH had fewer mental health diagnoses (rate ratio (RR) 0.81 (95% CI: 0.70-0.93); p=0.003) or medications prescribed for them (RR 0.62 (0.47-0.83); p=0.001). WLWH had a similar number of physical diagnoses (RR 1.03 (0.92-1.14; p=0.61) and medications for them (RR 1.03 (0.80-1.32; p=0.81). Adverse socio-structural experiences were significantly associated with higher number of concurrent illnesses and medication burden. Mental health conditions were associated with substance use, smoking, homelessness, and ethnicity; and their medication burden with substance use, smoking, hepatitis C, education and age. Physical conditions were associated with substance use, homelessness, hepatitis C and age; and their medication burden with substance use and age. All p<0.05.

Conclusions: In BCC3, adverse socio-structural experiences may have more impact on health and treatment than HIV status, suggesting a focus for patient care and advocacy.