Joseph Austin Christopher Delaney

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Objectives: High-risk alcohol use is associated with depressive symptoms. It is unclear if changes in alcohol use are correspondingly associated with changes in depression severity among people with HIV (PWH). Methods: Data were from clinical assessments of patient-reported outcomes (PROs) completed by PWH receiving primary care at 7 sites of the Center for AIDS Research Network of Integrated Clinical Systems. Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores, range (lower to higher risk): 0–12, and Patient Health Questionnaire-9 (PHQ-9) scores, range for depressive symptom burden: 0–27 (≥10 indicative of clinically relevant depression), from PROs were identified as observation pairs (PHQ-9 and AUDIT-C on the same day) occurring 1–2 years apart. We used linear regression with clustered standard errors to estimate the association between changes in AUDIT-C and changes in PHQ-9 stratified by baseline alcohol consumption. Results: A total of 7806 PWH contributed 13,302 observation pairs with a baseline mean age of 45.4 (SD: ±11.4); 15% were female and 55% identified with a non-White race/ethnicity. Each 1-point increase in AUDIT-C was associated with a 0.30-point (95% CI: 0.15–0.44), 0.26-point (95% CI: 0.14–0.37), and 0.20-point (95% CI: 0.10–0.30) increase in PHQ-9 for PWH with no alcohol use, low-to-moderate risk alcohol use, and high-risk alcohol use at baseline, respectively. Estimates were essentially stable after adjusting for sex, age, and race/ethnicity. Conclusions: There is a modest, statistically significant association between change in AUDIT-C and change in PHQ-9. These findings highlight the importance of routinely monitoring alcohol use and depression in HIV primary care settings. Future studies exploring causal directions are warranted.

Background Over the last decade, gabapentin has become one of the most utilized antiseizure medications during pregnancy, but association between gabapentin use during pregnancy and adverse neonatal outcomes among pregnant people with epilepsy (PPWE), and pregnant people without epilepsy (PPWOE) is not clear. Methods We conducted a retrospective population-based cohort study among pregnant people in Manitoba, between 1998 to 2021 to examine the association between gabapentin exposure in-utero and the risk of low birth weight (LBW), preterm birth, NICU admissions, maternal length of hospital stays (LOS), infants LOS, infant mortality, neonatal mortality, neonatal readmissions, neonatal respiratory distress syndrome, and severe neonatal morbidity. We performed crude, adjusted and high dimensional propensity scores (HDPS) analysis using generalised estimating equations with exchangeable matrix. Results Among 1057 pregnant people exposed to gabapentin, we found a significant increased risk of LBW (aOR 1.95, 95% CI 1.58-2.41), preterm birth (aOR 1.68, 95% CI 1.39-2.03), NICU admissions (aOR 2.04, 95% CI 1.71-2.42), pregnant peoples LOS (aOR 1.33, 95% CI 1.15-1.54), infant LOS (aOR 2.09, 95% CI 1.81-2.41) and neonatal respiratory distress syndrome (aOR 3.36, 95% CI 1.16-9.71). In exposed PPWE and PPWOE we found a significant increased risk of infant mortality aOR 5.39 (95% CI 1.11-26.2). The results from HDPS models showed attenuated estimates and non-significant results, suggesting strong unmeasured confounding among adjusted regression models. Conclusion We observed potential risk for specific neonatal outcomes, however unmeasured confounding can not be dismissed. Future studies on the effect of gabapentin during pregnancy are warranted.

Objectives: To understand the trade-offs between different statistical modeling approaches, using real world data with small sub-populations, with rare exposures and increasingly rare outcomes. In particular, to compare adjusted regression, inverse probability weighting, and matching. Methods: Data for these analyses came from the RADAR (N=1,134) and combined CNICS/JHHCC (N=14,434) cohorts. We estimated prevalence ratios (PRs) for self-reported use of specific substances comparing subpopulations (SP), SP-1 vs SP-3 and SP-2 vs SP-3, where SP-1 was the largest proportion (92% in RADAR, 81% in CNICS/JHHCC), SP2 was moderate proportion (18% in CNICS/JHHCC) and SP-3 was the smallest proportion (8% in RADAR, 1% in CNICS/JHHCC) of the population. We calculated PRs using 1) unadjusted relative risk regression (RR); and adjusted estimates controlling for age, race/ethnicity, study site, and year of interview using: 2) standard adjustment in RR; 3) stabilized inverse probability of treatment weighting (IPTW); and 4) matching with up to 3 matches from SP-1 or SP-2 per SP-3 participant. Results: For most substances, all methods yielded consistent estimates. There were large weights in some of the IPTW analyses and in three cases these resulted in substantially divergent estimates. For the comparison between SP-1 and SP-3, the estimate for smoking was 1.3-fold greater in the matched analysis (PR=1.33, 95% CI: 1.02-1.75) than in IPTW (PR=1.03, 95% CI: 0.78-1.37 ATE and PR=1.05, 95% CI: 0.88-1.26 ATT). Even more extreme divergence in estimates was observed for differences between SP-2 and SP-3 with respect to methamphetamine/amphetamine, (IPTW-ATE: PR=1.51, 95% CI: 0.79-2.89; IPTW-ATT: PR=2.36, 95% CI: 1.36-4.12); vs Matching: PR=2.71, 95%CI: 1.47-4.99) and cocaine (IPTW-ATE: PR=1.15, 95% CI: 0.55-2.38; IPTW-ATT: PR=1.81, 95% CI: 1.03-3.18); vs Matching: PR=1.38, 95%CI: 0.76-2.53). Conclusion: The combination of a rare exposure and a rare outcome can produce challenges for commonly used confounding adjustment strategies, and it is often best to compare different modeling approaches to gain greater insight.

Despite the recognition of substance use and sex work as public health issues, the intersection of these areas, especially within the rural US, is an area of special importance. The Rural Opioid Initiative comprises of eight research cohorts spanning 10 states and 65 rural US counties. Between 1/2018-3/2020, individuals who reported past 30-day substance injection or opioid misuse were recruited. Analyses were restricted to people who use drugs (PWUD) who reported trading “vaginal or anal sex for drugs, money, housing, or other things you need” in the past 30 days. We analyzed cross-sectional associations between injection drug use and sexual behaviors associated with hepatitis C virus (HCV)/HIV infection transmission, access to harm reduction, and HCV status among PWUD and engaged in sex work in rural US areas. Of the 2045 participants, 9% (n=180) reported engagement with sex work, with just over half being women (58% [n=104]). In adjusted models, people who engaged in sex work, compared to PWUD who did not, had higher prevalence ratios of past 30-day receptive syringe sharing (adjusted prevalence ratio [aPR]=1.69, 95% Confidence Interval [95%CI]=1.44–1.98), practice of multiple injections per injection episode (aPR = 1.28, 95% CI = 1.15–1.43), practice of syringe mediated drug sharing (aPR=1.50, 95% CI=1.32–1.71), condomless sex (aPR=1.62, 95% CI=1.48–1.77) and condomless sex with someone who injects drugs (aPR=2.05, 95% CI=1.76–2.39). PWUD engaged in sex work were less likely to report easy condom access (aPR=0.88, 95% CI=0.80–0.96), while no significant differences were observed for most other harm reduction access measures. PWUD engaged in sex work in the rural US had higher likelihood of injection drug use and sexual behaviors associated with HCV/HIV infection transmission, while having lower use of and access to condoms. This study emphasizes the importance of ensuring affordable access to condoms within the context of harm reduction services, especially given the limited access to health care and supportive services, particularly in rural communities.

People with HIV (PWH) have a high prevalence of obstructive sleep apnea (OSA), yet the condition receives minimal attention despite a high prevalence of OSA risk factors. PWH attending HIV care between 2008 and 2023 were eligible. Sleep studies were identified in electronic health records. We estimated associations between completion of a study and HIV factors and fatigue using adjusted relative risk regression. Among 3,977 PWH, 4% completed a sleep study. PWH who underwent sleep studies were older (50 vs. 48 years), fewer had low current CD4 cell counts (2% vs. 11% < 200 cells/mm ³ ), and more had HIV viral suppression (97% vs. 85%) than those who did not. Bothersome fatigue was associated with 2.9 times (95% confidence interval: 1.9–4.4) greater likelihood of completing a sleep study. Sleep studies are rarely conducted among PWH. PWH who received a sleep study had better HIV control (higher CD4 count/viral suppression) and a greater burden of fatigue and OSA-related comorbidities.

We examined cross-sectional and longitudinal associations of urinary isoprostanes with carotid T-PWV, and its associated mechanisms (S-PWV and LD-PWV), in a multiethnic cohort of adults. Higher isoprostanes were cross-sectionally associated with carotid artery stiffness driven by structural remodeling in adults who self-reported taking angiotensin-II acting medications or self-identified as White. No associations were observed with isoprostanes and carotid stiffness a decade later in the entire analytic sample. Oxidative stress may augment the risk of structural remodeling in select populations.

People with HIV (PWH) are at an increased risk of venous thromboembolism (VTE), and cannabis use is common in this population. However, evidence of cannabis impact on VTE risk has been conflicting and not well evaluated in PWH. Using data from five Centers for AIDS Research Network of Integrated Clinical Systems sites (2009–2020), we assessed the association between cannabis use and VTE risk. Among 13,646 PWH, 30% reported current cannabis use. In adjusted Cox models, neither former (adjusted hazard ratio [aHR] 0.78, 95% confidence interval (CI) 0.57–1.07) nor current (aHR 0.74, 95% CI 0.51–1.06) cannabis use showed a significant increase in VTE incidence compared with never use. Additionally, no dose-dependent relationship was observed between cannabis use frequency and VTE. Among PWH, cannabis use does not appear to be associated with an elevated risk of VTE. Further research is needed to elucidate the relationship between cannabis and VTE risk in this population.