The impact of diabetes mellitus on HIV virologic control: results of the MACS/WIHS combined cohort study.

OBJECTIVE: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown. METHODS: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/mL) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/mL) between adult PWH with and without DM. Poisson regression was used to examine the rate of incident viremia based on the diagnosis of DM among PWH. DM was defined as two consecutive fasting glucose measurements ≥126 mg/dL, use of anti-diabetic medications, pre-existing DM diagnosis, or a confirmed HbA1c >6.5%. RESULTS: 1,061 women (112 with DM, 949 without DM) and 633 men (41 with DM, and 592 without DM) were included in the analysis. The relative rate (RR) of incident HIV viremia for women with HIV and DM was lower when compared to women without DM (0.85 [95% CI: 0.72-0.99]; p = 0.04). The RR of incident viremia for women with uncontrolled DM (HbA1c>7.5%) was higher when compared to women with controlled DM (HbA1c <7.5%) (1.46 [95%CI: 1.03-2.07]; p = 0.03). In contrast, the RR of incident viremia for men with HIV and DM was not statistically different compared to men without DM (1.2 [95%CI: 0.96- 1.50]; p = 0.12). The results were stratified by adherence levels (100%, 95-99%, and less than 95% based on self-report). CONCLUSIONS: Women with DM who are highly adherent to ART (100% self-reported adherence) have a lower risk of viremia compared to women with HIV without DM. However, women with poorly controlled DM were at higher risk of HIV viremia than women with controlled DM. Further research is necessary to understand the impact of sex, DM, and ART adherence on HIV viremia.

Standardization and clinical applications of retinal imaging biomarkers for cardiovascular disease: a Roadmap from an NHLBI workshop.

The accessibility of the retina with the use of non-invasive and relatively low-cost ophthalmic imaging techniques and analytics provides a unique opportunity to improve the detection, diagnosis and monitoring of systemic diseases. The National Heart, Lung, and Blood Institute conducted a workshop in October 2022 to examine this concept. On the basis of the discussions at that workshop, this Roadmap describes current knowledge gaps and new research opportunities to evaluate the relationships between the eye (in particular, retinal biomarkers) and the risk of cardiovascular diseases, including coronary artery disease, heart failure, stroke, hypertension and vascular dementia. Identified gaps include the need to simplify and standardize the capture of high-quality images of the eye by non-ophthalmic health workers and to conduct longitudinal studies using multidisciplinary networks of diverse at-risk populations with improved implementation and methods to protect participant and dataset privacy. Other gaps include improving the measurement of structural and functional retinal biomarkers, determining the relationship between microvascular and macrovascular risk factors, improving multimodal imaging 'pipelines', and integrating advanced imaging with 'omics', lifestyle factors, primary care data and radiological reports, by using artificial intelligence technology to improve the identification of individual-level risk. Future research on retinal microvascular disease and retinal biomarkers might additionally provide insights into the temporal development of microvascular disease across other systemic vascular beds.

Hospital readmissions among adults living with and without HIV in the US: findings from the Nationwide Readmissions Database.

Background: Thirty-day hospital readmission measures quality of care, but there are limited data among people with HIV (PWH) and people without HIV (PWoH) in the era of universal recommendation for antiretroviral therapy. We descriptively compared 30-day all-cause, unplanned readmission risk between PWH and PWoH. Methods: A retrospective cohort study was conducted using the 2019 Nationwide Readmissions Database (2019/01/01-2019/12/31), an all-payer database that represents all US hospitalizations. Index (initial) admissions and readmissions were determined using US Centers for Medicare & Medicaid Services definitions. Crude and age-adjusted risk ratios (aRR) comparing the 30-day all-cause, unplanned readmission risk between PWH to PWoH were estimated using random effect logistic regressions and predicted marginal estimates. Survey weights were applied to all analyses. Findings: We included 24,338,782 index admissions from 18,240,176 individuals. The median age was 52(IQR = 40-60) years for PWH and 61(IQR = 38-74) years for PWoH. The readmission risk was 20.9% for PWH and 12.2% for PWoH (age-adjusted-RR:1.88 [95%CI = 1.84-1.92]). Stratified by age and sex, young female (age 18-29 and 30-39 years) PWH had a higher readmission risk than young female PWoH (aRR = 3.50 [95%CI = 3.11-3.88] and aRR = 4.00 [95%CI = 3.67-4.32], respectively). While the readmission risk increased with age among PWoH, the readmission risk was persistently high across all age groups among PWH. The readmission risk exceeded 30% for PWH admitted for hypertensive heart disease, heart failure, and chronic kidney disease. Interpretation: PWH have a disproportionately higher risk of readmission than PWoH, which is concerning given the aging profile of PWH. More efforts are needed to address readmissions among PWH. Funding: US National Institutes of Health.

Vision Problems As a Contributor to Lower Engagement in Care Among Aging Men Living with HIV.

PURPOSE: To investigate vision impairment as a barrier to engagement in medical care among aging persons living with HIV (PLWH) who experience multimorbidity and complex care needs. SETTING: Multicenter AIDS Cohort Study (MACS), a prospective observational cohort of aging PLWH men. METHODS: We examined relationships of self-reported vision difficulty with indicators of care engagement: 1) adherence to HIV antiretroviral therapy (ART; defined as taking ≥95% of medications); 2) self-reported avoidance of medical care; 3) self-reported tendency to ask a doctor questions about care (>2 questions at a medical visit), as well as with quality of life. A modified version of the National Eye Institute Vision Function Questionnaire was administered at three semi-annual visits (from October 2017 to March 2019) to assess difficulty performing vision-dependent tasks. RESULTS: We included 1063 PLWH (median age 57 years, 31% Black). Data on care engagement outcomes were analyzed using repeated measures logistic regression with generalized estimating equations adjusted for race, and at visit values for age, education level, depressive symptoms, alcohol use, and smoking status. Compared to no vision difficulty, those reporting moderate to extreme vision difficulty on at least one task had 2.2 times higher odds (95% CI: 1.4, 3.4) of having less than optimal ART adherence, 1.9 times higher odds (95% CI: 1.1, 3.4) of avoiding necessary medical care and median quality of life scores 8 points lower. CONCLUSION: These findings suggest vision impairment decreases medical care engagement including HIV care and quality of life among aging PLWH.

Improving Maternal Health Care Quality and Outcomes: Evaluation of a Pregnancy Medical Home.

Current maternal care recommendations in the United States focus on monitoring fetal development, management of pregnancy complications, and screening for behavioral health concerns. Often missing from these recommendations is support for patients experiencing socioeconomic or behavioral health challenges during pregnancy. A Pregnancy Medical Home (PMH) is a multidisciplinary maternal health care team with nurse navigators serving as patient advocates to improve the quality of care a patient receives and health outcomes for both mother and infant. Using bivariate comparisons between PMH patients and reference groups, as well as interviews with project team members and PMH graduates, this evaluation assessed the impact of a PMH at an academic medical university on patient care and birth outcomes. This PMH increased depression screenings during pregnancy and increased referrals to behavioral health care. This evaluation did not find improvements in maternal or infant birth outcomes. Interviews found notable successes and areas for program enhancement.

Effectiveness of mRNA Booster Vaccine Against Coronavirus Disease 2019 Infection and Severe Outcomes Among Persons With and Without Immune Dysfunction: A Retrospective Cohort Study of National Electronic Medical Record Data in the United States.

Background: Real-world evidence of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) booster effectiveness among patients with immune dysfunction are limited. Methods: We included data from patients in the United States National COVID Cohort Collaborative (N3C) who completed ≥2 doses of mRNA vaccination between 10 December 2020 and 27 May 2022. Immune dysfunction conditions included human immunodeficiency virus infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer. We defined incident COVID-19 BTI as positive results from laboratory tests or diagnostic codes 14 days after at least 2 doses of mRNA vaccination; and severe COVID-19 BTI as hospitalization, invasive cardiopulmonary support, and/or death. We used propensity scores to match boosted versus nonboosted patients and evaluated hazards of incident and severe COVID-19 BTI using Cox regression after matching. Results: Among patients without immune dysfunction, the relative effectiveness of booster (3 doses) after 6 months from the primary (2 doses) vaccination against BTI ranged from 69% to 81% during the Delta-predominant period and from 33% to 39% during the Omicron-predominant period. Relative effectiveness against BTI was lower among patients with immune dysfunction but remained statistically significant in both periods. Boosted patients had lower risk of COVID-19-related hospitalization (hazard ratios [HR] ranged from 0.5 [95% confidence interval {CI}, .48-.53] to 0.63 [95% CI, .56-.70]), invasive cardiopulmonary support, or death (HRs ranged from 0.46 [95% CI, .41-.52] to 0.63 [95% CI, .50-.79]) during both periods. Conclusions: Booster vaccines remain effective against severe COVID-19 BTI throughout the Delta- and Omicron-predominant periods, regardless of patients' immune status.

Patient barriers and facilitators for making environmental and behavioral modifications for dry eye in the United States.

BACKGROUND: Managing dry eye disease (DED) is expensive. Often, prescribed treatments improve clinical signs but not patient-reported symptoms. In large surveys, clinicians and patients ranked environmental and behavioral modifications among the most important DED-related research priorities. Our purpose was to investigate the barriers to and facilitators of use of these modifications by patients with DED in the United States and how their use may be impacted by socioeconomic status (SES). METHODS: Using Qualtrics, we conducted an anonymous online survey of adults with DED living in the United States in August to September 2022. Patients were identified through the Dry Eye Foundation, Sjögren's Foundation, and a DED clinic in Colorado. We used an established index for classifying respondent SES based on education, household income, and employment. Outcomes included use of environmental and behavioral modifications and barriers to and facilitators of their use. RESULTS: We included 754 respondents (SES: 382 low, 275 high, and 97 unclear). Most were aged 18 to 49 years (67%), female (68%), and White (76%) and reported dealing with DED for ≤5 years (67%). The most frequent modifications were taking breaks to rest eyes (68%), increasing water intake (68%), and using hot/cold compresses (52%). For these three, the biggest facilitators were as follows: belief that the modification works (27 to 37%), being recommended it (24 to 26%), and ease of use/performance (21 to 32%). Across modifications, the biggest barriers were difficulty of use (55%), lack of family/employer/social/community support (33%), and lack of awareness (32%). The data do not suggest discernible patterns of differences in barriers or facilitators by SES. CONCLUSIONS: Greater emphasis should be placed on explaining to patients how environmental and behavioral modifications might mitigate DED. Employers and members of patients' support systems should be guided regarding how best to support patients in managing DED symptoms.

Incident Proteinuria by HIV Serostatus Among Men With Pre--Diabetes Mellitus: The Multicenter AIDS Cohort Study.

BACKGROUND: Pre-diabetes mellitus (DM) is associated with proteinuria, a risk factor for chronic kidney disease. While people with human immunodeficiency virus (HIV; PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among prediabetic persons. METHODS: The urine protein-to-creatinine ratio was measured at semiannual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of antidiabetic medications were included. Pre-DM was defined as a fasting glucose level of 100-125 mg/dL confirmed within a year by a repeated fasting glucose or hemoglobin A1c measurement of 5.7%-6.4%. Incident proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) >200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-DM differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. RESULTS: Between 2006 and 2019, among 1276 men with pre-DM, proteinuria developed in 128 of 613 PWH (21%) and 50 of 663 PWOH (8%) over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-DM was 3.3 times (95% confidence interval, 2.3-4.8 times) greater than in PWOH (P < .01). Among PWH, current CD4 cell count <50/µL (P < .01) and current use of protease inhibitors (P = .03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. CONCLUSIONS: Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population.

Mediation analysis of chronic kidney disease risk factors using kidney biomarkers in women living with HIV.

OBJECTIVE: Novel urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in persons living with HIV. However, it is unknown whether these biomarkers provide mechanistic insight into the associations between clinical risk factors for CKD and subsequent CKD risk. METHODS: Among 636 women living with HIV in the Women's Interagency HIV Study with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m 2 , we used a counterfactual approach to causal mediation analysis to evaluate the extent to which systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin a1c (Hba1c) and serum albumin associations with incident CKD were mediated by eight urine proteins. These biomarkers reflect proximal tubular reabsorptive dysfunction (α1-microglobulin [a1m], ß2-microglobulin, trefoil factor 3); tubular injury (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1]); kidney repair (epidermal growth factor); tubular reserve (uromodulin); and glomerular injury (urinary albumin). Incident CKD was defined as eGFR <60 ml/min/1.73 m 2 measured at two consecutive 6-month visits with an average annual eGFR decline ≥3% per year. RESULTS: During a median follow-up of 7 years, 11% developed CKD. Urinary albumin and KIM-1 mediated 32% (95% CI: 13.4%, 76.6%) and 23% (6.9%, 60.7%) of the association between SBP and incident CKD, respectively; and 19% (5.1%, 42.3%) and 22% (8.1%, 45.7%) of the association between DBP and incident CKD, respectively. Urinary albumin, α1m, and IL-18 were significant mediators of the association between Hba1c and incident CKD. None of the eight biomarkers mediated the association between serum albumin and incident CKD. CONCLUSIONS: Among women living with HIV, several urinary biomarkers reflecting distinct dimensions of kidney health may partially explain the associations between SBP, DBP, and Hba1c and subsequent CKD risk.

Social Determinants of Dry Eye in the United States: A Systematic Review.

PURPOSE: To conduct a systematic review to summarize current evidence on associations between social determinants of health (SDOH) indicators and dry eye in the United States. DESIGN: Systematic review. METHODS: We followed a protocol registered on Open Science Framework to include studies that examined associations between SDOH indicators and dry eye. We mapped SDOH indicators to 1 of the 5 domains following the Healthy People 2030 framework and categorized dry eye measures into "dry eye diagnosis and care," "dry eye symptoms," or "ocular surface parameters." We summarized the direction of association between SDOH indicators and dry eye as worsening, beneficial, or null. We used items from the Newcastle Ottawa Scale to assess risk of bias. RESULTS: Eighteen studies reporting 51 SDOH indicators, mostly mapped to the neighborhood and built environment domain, were included. Thirteen studies were judged at high risk of bias. Fifteen of 19 (79%) associations revealed an increase in the diagnosis of dry eye or delayed specialty care for it. Thirty-four of 56 (61%) associations unveiled exacerbated dry eye symptoms. Fifteen of 23 (65%) found null associations with corneal fluorescein staining. Ten of 22 (45%) associations revealed an increased tear break up time (45%) whereas another 10 (45%) showed null associations. CONCLUSIONS: Most SDOH indicators studied were associated with unfavorable dry eye measures, such as a higher disease burden, worse symptoms, or delayed referral, in the United States. Future investigations between SDOH and dry eye should use standardized instruments and address the domains in which there is an evidence gap.