Sex Differences in the Risk of Stroke Associated With Traditional and Non-Traditional Factors in a US Cohort of People With HIV Infection.

BACKGROUND AND OBJECTIVES: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke. RESULTS: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk. DISCUSSION: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.

Prevalence and Correlates of SARS-CoV-2 Vaccine Uptake and Hesitancy Among People With HIV Across the United States.

BACKGROUND: People with HIV (PWH) have higher risk of COVID-19 mortality. SARS-CoV-2 vaccination is highly effective among PWH, although vaccine hesitancy could limit the population-level impact. SETTING: From February 2021 to April 2022, PWH from 8 sites in the Centers for AIDS Research Network of Integrated Clinical Systems completed a vaccine hesitancy instrument as part of routine care. METHODS: Participants were defined as vaccine hesitant if they had not received the SARS-CoV-2 vaccine and would probably/definitely not receive it. We assessed factors associated with SARS-CoV-2 vaccine hesitancy using logistic regression adjusted for demographics, unsuppressed viral load (VL > 200 copies/mL), month, and time on ART; using inverse probability weighting for survey nonresponse. RESULTS: Overall, 3288 PWH with a median age of 55 were included; 18% were female and 94% were virally suppressed. At the time of survey, 27% reported they had not received the SARS-CoV-2 vaccine, and 9% (n = 279) reported vaccine hesitancy. Factors associated with vaccine hesitancy included female sex (adjusted odds ratio [AOR] = 2.3; 95% confidence interval (CI): 1.6-3.2), Black vs. White race (AOR 1.7; 95% CI: 1.2 to 2.4), younger age (AOR 1.4; 95% CI: 1.2 to 1.5), and unsuppressed VL (AOR 1.9; 95% CI: 1.3 to 3.0). CONCLUSION: Overall, over one-quarter of PWH in this multisite cohort were unvaccinated for SARS-CoV-2 when interviewed February 21-April 22. Vaccine hesitancy was reported by approximately 9% of PWH and was higher among women, Black PWH, younger PWH, PWH with unsuppressed VL, and those in the South/Midwest. Renewed efforts are needed to address concerns of PWH about vaccinations against COVID-19 as the pandemic evolves, and vaccines in general, given the potential for future pandemics.

Demographic, clinical, and social characteristics of anal cancer among patients stratified by age (<50 and ≥50 years) in Alabama between 2012 and 2018.

BACKGROUND: Anal cancer is increasing globally, with a high number of new cases occurring in highly developed countries, including the U.S. The incidence of anal cancer is higher among people living with HIV (PLHIV), and the U.S. South continues to see higher HIV incidence rates and lagging HPV vaccination rates. We aimed to identify factors associated with early onset anal cancer in Alabama which may help explain cancer disparities in the South. METHODS: Using a cross-sectional study design, we examined demographic, clinical, and social characteristics among anal cancer patients stratified by diagnosis age (<50 and ≥50 years) in the Alabama cancer registry between 2012 and 2018. We used Wilcoxon rank sums and Pearson chi-square tests to assess associations between age at diagnosis, demographic (i.e., sex, race, marital status), clinical (i.e., BMI, HIV infection, site, stage, and histological type), and social (i.e. social vulnerability) characteristics, and multivariable logistic regression to estimate the odds of early onset cancer. RESULTS: Among 519 patients with anal cancer in Alabama, 92 (17.7 %) were diagnosed at <50 years. The majority of patients were female (66.5 %) and White (83.4 %). Male sex, Black race, and HIV infection were associated with younger age at diagnosis. Black patients had a 4-fold increased odds of early onset anal cancer compared to White patients (AOR=4.39, CI=1.54-12.49). Black patients disproportionately lived in areas with higher social vulnerability. About 42 % of patients in areas with the highest social vulnerability were diagnosed with stage 3 or 4 cancer. About 8 % of cases were among people aged 35-44 years, which is close to double the proportion of anal cancer cases in this age group in the U.S. (4.7 %). CONCLUSIONS: Patients who are Black, male, and PLHIV may be at higher risk of early onset anal cancer compared to other populations in the South.

Association of Integrase Strand Transfer Inhibitor-Based Antiretroviral Therapy with Blood Pressure and Sustained Hypertension in People with HIV.

BACKGROUND: Integrase strand transfer inhibitors (INSTI) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP). METHODS: We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic. Office BP was measured unattended using an automated (AOBP) device. Awake, asleep and 24-hour BP were measured through ambulatory BP monitoring. Among participants with SBP ≥130 mmHg or DBP≥80 mmHg on AOBP, sustained hypertension was defined as awake SBP≥130 mmHg or DBP≥80 mmHg. RESULTS: Mean SBP and DBP was higher among participants taking INSTI-based versus non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 versus 135.3/79.3 mmHg; awake-SBP/DBP: 143.2/80.9 versus 133.4/76.3 mmHg; asleep-SBP/DBP: 133.3/72.9 versus 120.3/65.4 mmHg; 24-hour-SBP/DBP: 140.4/78.7 versus 130.0/73.7 mmHg). After multivariable adjustment, AOBP, awake, asleep and 24-hour SBP was 12.5 (95%CI 5.0-20.1), 9.8 (95%CI 3.6-16.0), 10.4 (95%CI 2.0-18.9), and 9.8 (95%CI 4.2-15.4) mmHg higher among those taking INSTI-based versus non-INSTI-based ART, respectively. AOBP, awake, asleep and 24-hour DBP was 7.5 (95%CI 0.3-14.6), 6.1 (95%CI 0.3-11.8), 7.5 (95%CI 1.4-13.6), and 6.1 (95%CI 0.9-11.3) mmHg higher among those taking INSTI-based versus non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mmHg or DBP≥80 mmHg on AOBP and 97.9% and 65.7% of participants taking INSTI-based and non-INSTI-based ART had sustained hypertension, respectively. CONCLUSION: INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART.

Viral Suppression Trajectories Destabilized After Coronavirus Disease 2019 Among US People With Human Immunodeficiency Virus: An Interrupted Time Series Analysis.

We examined changes in the proportion of people with human immunodeficiency virus (PWH) with virologic suppression (VS) in a multisite US cohort before and since the coronavirus disease 2019 (COVID-19) pandemic. Overall, prior gains in VS slowed during COVID-19, with disproportionate impacts on Black PWH and PWH who inject drugs.

Brief Report: Relationship Between Adiposity and Biomarkers of Aging and Frailty Among Adults Aging With HIV.

BACKGROUND: This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV. METHODS: This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone-binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function. RESULTS: Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (ß = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (ß = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (ß = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (ß = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (ß = -0.004, P = 0.01); no statistically significant associations were observed for handgrip. CONCLUSION: Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older.

Undertreatment of opioid use disorder in patients hospitalized with injection drug use-associated infections.

OBJECTIVE: To evaluate the association between medication for opioid use disorder (MOUD) initiation and addiction consultation and outcomes for patients hospitalized with infectious complications of injecting opioids. METHOD: This was a retrospective cohort study performed at four academic medical centers in the United States. The participants were patients who had been hospitalized with infectious complications of injecting opioids in 2018. Three hundred and twenty-two patients were included and their individual patient records were manually reviewed to identify inpatient receipt of medication for opioid use disorder (MOUD), initiation of MOUD, and addiction consultation. The main outcomes of interest were premature discharge, MOUD on discharge, linkage to outpatient MOUD, one-year readmission and death. RESULTS: Three hundred and twenty-two patients were predominately male (59%), white (66%), and median age 38 years, with 36% unstably housed, and 30% uninsured. One hundred and forty-five (45%) patients received MOUD during hospitalization, including only 65 (28%) patients not on baseline MOUD. Discharge was premature for 64 (20%) patients. In the year following discharge, 27 (9%) patients were linked to MOUD, and 159 (50%) patients had at least one readmission. Being on MOUD during hospitalization was significantly associated with higher odds of planned discharge [odds ratio (OR) 3.87, P  < 0.0001], MOUD on discharge (OR 129.7, P  < 0.0001), and linkage to outpatient MOUD (OR 1.25, P  < 0.0001), however, was not associated with readmission. Study limitations were the retrospective nature of the study, so post-discharge data are likely underestimated. CONCLUSION: There was dramatic undertreatment with MOUD from inpatient admission to outpatient linkage, and high rates of premature discharge and readmission. Engagement in addiction care during hospitalization is a critical first step in improving the care continuum for individuals with opioid use disorder; however, additional interventions may be needed to impact long-term outcomes like readmission.

RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV.

BACKGROUND: Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT. METHODS: We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA). RESULTS: There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA.Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

Trends in diabetes incidence and associated risk factors among people with HIV in the current treatment era.

OBJECTIVE: To examine type 2 diabetes mellitus incidence and associated risk factors among people with HIV (PWH). DESIGN: A retrospective clinical cohort study of PWH at a Southeastern US academic HIV clinic between 2008 and 2018. METHODS: PWH who attended at least two clinic visits were evaluated with demographic and clinical data extracted from the electronic medical record (EMR). Diabetes was defined as: hemoglobin A1C ≥6.5% and/or 2 glucose results >200 mg/dl (at least 30 days apart), diagnosis of diabetes in the EMR, or exposure to diabetes medication. Time to diabetes incidence was computed from the entire clinic population for each year. Multivariable Cox proportional hazard regression models with time-dependent covariates were created to evaluate the independent association between covariates and time to incident diabetes. RESULTS: Among 4113 PWH, we identified 252 incident cases of diabetes. Incidence increased from 1.04 incidents per 1000 person years (PY) in 2008, to 1.55 incidents per 1000 PY in 2018. Body mass index (hazard ratio [HR] 10.5 (6.2, 17.7)), liver disease (HR 1.9 (1.2, 3.1)), steroid exposure (HR 1.5 (1.1, 1.9)), and use of integrase inhibitors (HR 1.5 (1.1, 2.0)) were associated with incident diabetes. Additional associated factors included lower CD4 + cell counts, duration of HIV infection, exposure to nonstatin lipid-lowering therapy, and dyslipidemia. CONCLUSIONS: Rapidly increasing incident diabetes rates among PWH were associated with both traditional and HIV-related associated risk factors, particularly body weight, steroid exposure, and use of Integrase Inhibitors. Notably, several of the risk factors identified are modifiable and can be targeted for intervention.

COVID Community-Engaged Testing in Alabama: Reaching Underserved Rural Populations Through Collaboration.

Rural communities are often underserved by public health testing initiatives in Alabama. As part of the National Institutes of Health's Rapid Acceleration of Diagnostics‒Underserved Populations initiative, the University of Alabama at Birmingham, along with community partners, sought to address this inequity in COVID-19 testing. We describe the participatory assessment, selection, and implementation phases of this project, which administered more than 23 000 COVID-19 tests throughout the state, including nearly 4000 tests among incarcerated populations. (Am J Public Health. 2022;112(10):1399-1403. https://doi.org/10.2105/AJPH.2022.306985).

Risk Factors for Incident Hypertension Within 1 Year of Initiating Antiretroviral Therapy Among People with HIV.

Hypertension (HTN) is a common comorbidity among people with HIV and associated with an increased risk for atherosclerotic cardiovascular disease and chronic kidney disease. The relationship of antiretroviral therapy (ART) initiation to incident HTN remains a clinical question. We determined HTN incidence at 48 weeks of follow-up among ART-naive participants without HTN and not taking antihypertensive medications at ART initiation through randomized clinical trials through the AIDS Clinical Trial Group between 1999 and 2011. We assessed the association of baseline characteristics, including randomized ART agents with HTN incidence at 48 weeks using Poisson regression models. Incident HTN was defined as blood pressure ≥130/80 mmHg, or use of antihypertensive medication. Among 2,614 participants, mean age was 37 ± 10 years, 79% male sex, and 36% African American race. After 48 weeks, 839 participants (32%) developed HTN. Receiving a non-nucleoside reverse transcriptase inhibitor (NNRTI) was associated with an increased relative risk (RR) of incident HTN, while the risk was lower for protease inhibitor use. Stavudine and efavirenz were associated with an increased RR of developing HTN, while tenofovir disoproxil fumarate, darunavir/ritonavir, and atazanavir/ritonavir were associated with a decreased risk of developing HTN. Additionally, older age, higher body mass index (BMI), and having hepatitis C were associated with an increased risk for developing HTN, while women and participants with a higher baseline CD4 count were at a decreased risk of developing HTN at 48 weeks. One third of these ART naive participants developed HTN after ART initiation. NNRTIs, notably efavirenz, and stavudine were associated with an increased risk of HTN. Additional factors associated with HTN included traditional factors like older age and higher BMI, and advanced HIV disease (lower CD4 count). (Clinicaltrials.gov: NCT00001137).

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort.

Among 14 049 people with human immunodeficiency virus in care in 2019-2020, 96% were treated with antiretroviral therapy (ART). Current antiretroviral treatment patterns highlight high uptake of guideline-recommended ART regimens including second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) and tenofovir alafenamide, especially in antiretroviral-naive individuals initiating ART.

Brief Report: Insomnia and Risk of Myocardial Infarction Among People With HIV.

BACKGROUND: Insomnia is common among people with HIV (PWH) and may be associated with increased risk of myocardial infarction (MI). This study examines the association between insomnia and MI by MI type among PWH. SETTING: Longitudinal cohort study of PWH at 5 Centers for AIDS Research Network of Integrated Clinical Systems sites. METHODS: Clinical data and patient-reported measures and outcomes from PWH in care between 2005 and 2018 were used in this study. Insomnia, measured at baseline, was defined as having difficulty falling or staying asleep with bothersome symptoms. The Centers for AIDS Research Network of Integrated Clinical Systems centrally adjudicates MIs using expert reviewers, with distinction between type 1 MI (T1MI) and type 2 MI (T2MI). Associations between insomnia and first incident MI by MI type were measured using separate Cox proportional hazard models adjusted for age, sex, race/ethnicity, traditional cardiovascular disease risk factors (hypertension, dyslipidemia, poor kidney function, diabetes, and smoking), HIV markers (antiretroviral therapy, viral suppression, and CD4 cell count), and stimulant use (cocaine/crack and methamphetamine). RESULTS: Among 12,448 PWH, 48% reported insomnia. Over a median of 4.4 years of follow-up, 158 T1MIs and 109 T2MIs were identified; approximately half of T2MIs were attributed to sepsis or stimulant use. After adjustment for potential confounders, we found no association between insomnia and T1MI (hazard ratio = 1.05, 95% confidence interval: 0.76 to 1.45) and a 65% increased risk of T2MI among PWH reporting insomnia compared with PWH without insomnia (hazard ratio = 1.65, 95% confidence interval: 1.11 to 2.45). CONCLUSIONS: PWH reporting insomnia are at an increased risk of T2MI, but not T1MI, compared with PWH without insomnia, highlighting the importance of distinguishing MI types among PWH.

HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis.

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts. METHODS: Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD. RESULTS: Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD. CONCLUSIONS: There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.

Healthcare is a Team Sport: Stress, Resilience, and Correlates of Well-Being Among Health System Employees in a Crisis.

EXECUTIVE SUMMARY: While the COVID-19 pandemic has added stressors to the lives of healthcare workers, it is unclear which factors represent the most useful targets for interventions to mitigate employee distress across the entire healthcare team. A survey was distributed to employees of a large healthcare system in the Southeastern United States, and 1,130 respondents participated. The survey measured overall distress using the 9-item Well-Being Index (WBI), work-related factors, moral distress, resilience, and organizational-level factors. Respondents were also asked to identify major work, clinical, and nonwork stressors. Multivariate regression was used to evaluate associations between employee characteristics and WBI distress score. Overall, 82% of employees reported high distress (WBI ≥ 2), with nurses, clinical support staff, and advanced practice providers reporting the highest average scores. Factors associated with higher distress included increased job demands or responsibilities, heavy workload or long hours, higher frequency of moral distress, and loneliness or social isolation. Factors associated with lower distress were perceived organizational support, work control, perceived fairness of salary cuts, and resilience. Most factors significantly associated with distress-heavy workloads and long hours, increased job demands, and moral distress, in particular-were work-related, indicating that efforts can be made to mitigate them. Resilience explained a small portion of the variance in distress relative to other work-related factors. Ensuring appropriate staffing levels may represent the single largest opportunity to significantly move the needle on distress. However, the financial impact of the COVID-19 pandemic on the healthcare system may represent a barrier to addressing these stressors.

Human papillomavirus sequencing reveals its usefulness for the management of HIV-infected women at risk for developing cervical cancer.

AIM: Next-generation sequencing (NGS) is able to describe the composition of human papillomaviruses (HPVs) as percent (%) reads rather than positive/negative results. Therefore, we used this unique approach to assess the prevalence of cervical HPVs of HIV infected (HIV+) in order to understand the determinants of being infected with higher % reads of high risk (HR)-HPVs and cervical abnormalities of atypical squamous cells of unknown significance or higher (ASCUS+). METHODS: Study included 66 women characterized for relevant risk factors/cytology. Receiver-operating curve curve was used to derive the optimal % read cut point to identify ASCUS+ in relation to any HR-HPV genotype or other specific HPV genotypes. The determinants of ASCUS+ and HR-HPVs were tested using logistic regression. RESULTS: Women with >20% reads of any HR-HPV or >12% any HR-HPV other than HPV 16/18 were 5.7 and 12.6 times more likely to be diagnosed with ASCUS+, respectively. Lower CD4 count was a significant determinant of >20% reads of HR-HPV (odds ratio [OR] = 4.1) or >12% any HR-HPV other than HPV 16/18 (OR = 4.5). CONCLUSION: We envision that the NGS-based HPV detection will be more accurate for screening and management of HIV+ at risk for developing cervical cancer (CC). We raise concerns regarding the limitations of 16/18-based HPV testing for triage and the efficacy of current HPV vaccines for preventing CC in HIV+.

Types of Stroke Among People Living With HIV in the United States.

BACKGROUND: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes. SETTING: CNICS, a U.S. multisite clinical cohort of PLWH in care. METHODS: We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort. RESULTS: Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes. CONCLUSION: Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.

Practice Transformation in HIV Primary Care: Perspectives of Coaches and Champions in the Southeast United States.

INTRODUCTION/OBJECTIVES: Across the United States, and particularly in the South, there is an urgent need to improve health outcomes for people with HIV. In response, the Southeast AIDS Education & Training Center (AETC) conducted a 4-year Practice Transformation (PT) initiative (2015-2018) in 12 mostly primary care clinics across 4 states in the region. Drawing on the leadership of PT facilitators ("coaches") from AETC partner sites throughout the region and specific clinic staff members ("champions"), clinics worked toward self-selected organizational goals to increase their HIV care capacity and improve HIV health outcomes. METHODS: To explore coaches' and champions' experiences and perspectives of PT, we conducted 2 focus group sessions, 1 tailored for coaches (n = 5) and another for champions (n = 9). RESULTS: Content analysis of qualitative data revealed 4 major themes around coaches' and champions' experiences and perspectives of PT. These themes include Challenges, Facilitators, Successes, and Suggestions for PT Improvement. CONCLUSION: Primary care and infectious diseases/HIV clinics can help improve HIV Care Continuum outcomes through increasing their capacity to serve the needs of their clients, as facilitated through coaches and clinic champions. Since no single clinic or clinic patient population is alike, it is important work within organizations to address specific needs and leverage unique skillsets. Future PT initiatives can learn from experiences of this PT program to optimize the effectiveness of their programs.