Overdose responses among rural people who use drugs: A multi-regional qualitative study.

BACKGROUND: Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy. METHODS: The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose. RESULTS: Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement. CONCLUSION: People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical.

Care interruptions and mortality among adults in Europe and North America: a collaborative analysis of cohort studies.

OBJECTIVE: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART. DESIGN: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004-2019. METHODS: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/pre-interruption or post-interruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care. RESULTS: Of 89197 PWH, 83.4% were male and median age at ART start was 39 years (interquartile range [IQR]: 31-48). 8654 PWH (9.7%) had ≥1 care interruption; 10913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536,334 person-years, a crude mortality rate of 11.4 (95%CI: 11.1-11.7) per 1000 person-years. The adjusted mortality hazard ratio (HR) for the post-interruption group was 1.72 (95%CI: 1.57-1.88) compared with the no/pre-interruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95%CI: 1.40-1.60) and ≥545-day (HR 1.67, 95%CI: 1.48-1.88) interruptions. CONCLUSIONS: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care.

Estimating the Proportion of People Living With HIV Who May Benefit From the Reverse Algorithm for the Diagnosis of Incident Syphilis.

ABSTRACT: Among 8455 people engaged in HIV care in 4 US cities, 4925 (58%) had treponemal testing at care entry. Of the 4925 tested, 3795 (77%) had a nonreactive result and might benefit from the reverse algorithm for a future incident syphilis diagnosis. Furthermore, low-barrier treponemal testing as a first step in the reverse algorithm may increase syphilis screening and decrease time to treatment.

The relationship between felt stigma and non-fatal overdose among rural people who use drugs.

BACKGROUND: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs. METHODS: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose. RESULTS: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14). CONCLUSIONS: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk.

Evaluation of respondent-driven sampling in seven studies of people who use drugs from rural populations: findings from the Rural Opioid Initiative.

BACKGROUND: Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. METHODS: RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. RESULTS: Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. CONCLUSIONS: RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.

Impact of the COVID-19 pandemic on mental health and viral suppression among persons living with HIV in western Washington.

The COVID-19 pandemic and social distancing measures elevated stress levels globally, exacerbating mental health challenges for people with HIV (PWH). We examined the effect of COVID-19-related stress on mental health among PWH in western Washington, exploring whether social support and coping self-efficacy were protective. Data on COVID-19-related stress, mental health, social support, and coping self-efficacy were collected using online surveys during the pandemic. Pre-COVID-19 mental health data were available for a subset of participants and were linked with the survey data. In the total sample (N = 373), COVID-19-stress was associated with elevated depression (PHQ-8, ß = 0.21, 95%CI [0.10, 0.32]) and anxiety (GAD-7, ß = 0.28, 95%CI [0.17, 0.39]). Among the subset of respondents with pre-pandemic mental health data (N = 103), COVID-19-related stress was associated with elevated PHQ-8 scores (ß = 0.35, 95%CI [0.15, 0.56]) and GAD-7 scores (ß = 0.35, 95%CI [0.16, 0.54]), adjusted for baseline mental health and other confounders. Coping self-efficacy was negatively associated with GAD-7 scores (ß = -0.01, 95%CI [-0.01, 0.00]), while social support was negatively associated with PHQ-8 scores (ß = -0.06, 95%CI [-0.12, -0.01]). Viral suppression before and during the pandemic did not differ among participants with available data. While COVID-19-related stress predicted elevated depression and anxiety symptoms among PWH, social support and coping self-efficacy were protective.

Incidence of non-AIDS defining comorbidities among young adults with perinatally-acquired HIV in North America, 2000-2019.

OBJECTIVE: To describe the incidence of diabetes mellitus type 2 (T2DM), hypercholesterolemia, hypertriglyceridemia, hypertension, and chronic kidney disease (CKD) from 2000 to 2019 among North American adults with perinatally-acquired HIV (PHIV) aged 18 to 30. DESIGN: Description of outcomes based on electronic health records for a cohort of 375 young adults with PHIV enrolled in routine HIV care at clinics contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: We estimated overall, sex-, and race-stratified cumulative incidences using Turnbull estimation, and incidence rates using quasi-Poisson regression. T2DM was defined as glycosylated hemoglobin >6.5% or based on clinical diagnosis and medication use. Hypercholesterolemia was based on medication use or total cholesterol ≥200 mg/dL. Hypertriglyceridemia was based on medication use or fasting triglyceride ≥150 mg/dL or non-fasting ≥200 mg/dL. Hypertension was based on clinical diagnosis. CKD was defined as estimated glomerular filtration rates <90 ml/mi|1.73 m2 for ≥3 months. RESULTS: Cumulative incidence by age 30 and incidence rates from age 18 to 30 (per 100 person-years) were: T2DM: 19%, 2.9; hypercholesterolemia: 40%, 4.6; hypertriglyceridemia: 50%, 5.6; hypertension: 22%, 2.0; and CKD: 25%, 3.3. Non-Black females had the highest incidence of hypercholesterolemia and hypertriglyceridemia, Black adults had the highest hypertension incidence, and Black males had the highest CKD incidence. CONCLUSION: There was a high incidence of five chronic comorbidities among people with PHIV. Earlier screening at younger ages might be considered for this unique population to strengthen prevention strategies and initiate treatment in a timely way.

Differences in internalized HIV stigma across subpopulations of people with HIV in care across the United States.

BACKGROUND: Few studies have examined which subgroups of people with HIV (PWH) carry the greatest burden of internalized HIV stigma (IHS), which may be important to care provision and interventions. METHODS: PWH in the CFAR Network of Integrated Clinical Systems (CNICS) longitudinal, US-based, multisite, clinical care cohort completed tablet-based assessments during clinic visits including a four-item, Likert scale (low 1-5 high), IHS instrument. Associations between sociodemographic characteristics and IHS scores were assessed in adjusted linear regression models. RESULTS: Twelve thousand six hundred and fifty-six PWH completed the IHS assessment at least once from February 2016 to November 2022, providing 28 559 IHS assessments. At baseline IHS assessment, the mean age was 49 years, 41% reported White, 38% Black/African American, and 16% Latine race/ethnicity, and 80% were cisgender men. The mean IHS score was 2.04, with all subgroups represented among those endorsing IHS. In regression analyses, younger PWH and those in care fewer years had higher IHS scores. In addition, cisgender women vs. cisgender men, PWH residing in the West vs. the Southeast, and those with sexual identities other than gay/lesbian had higher IHS scores. Compared with White-identifying PWH, those who identified with Black/African American or Latine race/ethnicity had lower IHS scores. Age stratification revealed patterns related to age category, including specific age-related differences by gender, geographic region and race/ethnicity. DISCUSSION: IHS is prevalent among PWH, with differential burden by subgroups of PWH. These findings highlight the benefits of routine screening for IHS and suggest the need for targeting/tailoring interventions to reduce IHS among PWH.

Association of Alcohol Use with COVID-19 Infection and Hospitalization Among People Living with HIV in the United States, 2020.

Alcohol use was associated with elevated COVID-19 risk in the general population. People with HIV (PWH) have high prevalences of alcohol use. To evaluate the effect of alcohol use on COVID-19 risks among PWH, we estimated the risk of COVID-19 diagnosis and COVID-19-related hospitalization among PWH in routine care at 8 HIV primary care centers that contributed data to the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort according to their alcohol use just prior to the COVID-19 pandemic. The CNICS data repository includes demographic characteristics, clinical diagnoses, and laboratory test results from electronic medical records and other sources. Alcohol use, substance use, and mental health symptoms were self-reported on tablet-based standardized surveys. Alcohol use was categorized according to standard, sex-specific Alcohol Use Disorder Identification Test-Consumption instrument cut-offs. We followed 5,496 PWH (79% male, 48% Black race, median age = 53 years) from March 1, 2020 to December 31, 2020. Relative to PWH with no baseline alcohol use, the adjusted hazard ratio (aHR) of COVID-19 diagnosis was 1.09 (95% confidence interval [CI]: 0.78, 1.51) for lower-risk drinking and 1.19 (95%CI: 0.81, 1.73) for unhealthy drinking. The aHR of COVID-19-related hospitalization was 0.82 (95%CI: 0.33, 1.99) for lower-risk drinking and 1.25 (95%CI: 0.50, 3.09) for unhealthy drinking. Results were not modified by recent cocaine or non-prescribed opioid use, depressive symptoms, or diagnoses of alcohol use disorder. The study suggested a slightly increased, but not statistically significant risk of COVID-19 diagnosis and hospitalization associated with unhealthy alcohol use.

The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study.

BACKGROUND: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. METHODS AND FINDINGS: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts. CONCLUSIONS: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.

BACKGROUND: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. METHODS: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. FINDINGS: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99). INTERPRETATION: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Correlates of Recent HIV Testing Among People Who Inject Drugs in Rural Areas: A Multi-site Cross-Sectional Study, 2018-2020.

The Rural Opioid Initiative surveyed 2693 people who inject drugs (PWID) in eight rural U.S. areas in 2018-2020 about self-reported HIV testing in the past 6 months. Correlates of interest included receipt of any drug-related services, incarceration history, and structural barriers to care (e.g., lack of insurance, proximity to syringe service programs [SSP]). Overall, 20% of participants reported receiving an HIV test within the past 6 months. Multivariable generalized estimating equations showed that attending substance use disorder (SUD) treatment (OR 2.11, 95%CI [1.58, 2.82]), having health insurance (OR 1.42, 95%CI [1.01, 2.00]) and recent incarceration (OR 1.49, 95%CI [1.08, 2.04]) were positively associated with HIV testing, while experiencing a resource barrier to healthcare (inability to pay, lack of transportation, inconvenient hours, or lack of child care) had inverse (OR 0.73, 95%CI [0.56, 0.94]) association with HIV testing. We found that the prevalence of HIV testing among rural PWID is low, indicating an unmet need for testing. While SUD treatment or incarceration may increase chances for HIV testing for rural PWID, other avenues for expanding HIV testing, such as SSP, need to be explored.

Venous Thromboembolism Among People With HIV: Design, Implementation, and Findings of a Centralized Adjudication System in Clinical Care Sites Across the United States.

BACKGROUND: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era. METHODS: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking. RESULTS: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common. CONCLUSIONS: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common.

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.

Weight loss associated with semaglutide treatment among people with HIV.

OBJECTIVE: There is limited real-world evidence about the effectiveness of semaglutide for weight loss among people with HIV (PWH). We aimed to investigate weight change in a US cohort of PWH who initiated semaglutide treatment. DESIGN: Observational study using the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: We identified adult PWH who initiated semaglutide between 2018 and 2022 and with at least two weight measurements. The primary outcome was within-person bodyweight change in kilograms at 1 year. The secondary outcome was within-person Hemoglobin A1c percentage (HbA1c) change. Both outcomes were estimated using multivariable linear mixed model. RESULTS: In total, 222 new users of semaglutide met inclusion criteria. Mean follow-up was 1.1 years. Approximately 75% of new semaglutide users were men, and at baseline, mean age was 53 years [standard deviation (SD): 10], average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (viral load < 50 copies/ml). In the adjusted mixed model analysis, treatment with semaglutide was associated with an average weight loss of 6.47 kg at 1 year (95% CI -7.67 to -5.18) and with a reduction in HbA1c of 1.07% at 1 year (95% CI -1.64 to -0.50) among the 157 PWH with a postindex HbA1c value. CONCLUSION: Semaglutide was associated with significant weight loss and HbA1c reduction among PWH, comparable to results of previous studies from the general population.

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz-Based Therapy in People With HIV Who Smoke.

Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P < 0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

ABSTRACT: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

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.

Recent Incarceration, Substance Use, Overdose, and Service Use Among People Who Use Drugs in Rural Communities.

Importance: Drug use and incarceration have a substantial impact on rural communities, but factors associated with the incarceration of rural people who use drugs (PWUD) have not been thoroughly investigated. Objective: To characterize associations between recent incarceration, overdose, and substance use disorder (SUD) treatment access among rural PWUD. Design, Setting, and Participants: For this cross-sectional study, the Rural Opioid Initiative research consortium conducted a survey in geographically diverse rural counties with high rates of overdose across 10 US states (Illinois, Wisconsin, North Carolina, Oregon, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire, and Vermont) between January 25, 2018, and March 17, 2020, asking PWUD about their substance use, substance use treatment, and interactions with the criminal legal system. Participants were recruited through respondent-driven sampling in 8 rural US regions. Respondents who were willing to recruit additional respondents from their personal networks were enrolled at syringe service programs, community support organizations, and through direct community outreach; these so-called seed respondents then recruited others. Of 3044 respondents, 2935 included participants who resided in rural communities and reported past-30-day injection of any drug or use of opioids nonmedically via any route. Data were analyzed from February 8, 2022, to September 15, 2023. Exposure: Recent incarceration was the exposure of interest, defined as a report of incarceration in jail or prison for at least 1 day in the past 6 months. Main Outcomes and Measures: The associations between PWUD who were recently incarcerated and main outcomes of treatment use and overdose were examined using logistic regression. Results: Of 2935 participants, 1662 (56.6%) were male, 2496 (85.0%) were White; the mean (SD) age was 36 (10) years; and in the past 30 days, 2507 (85.4%) reported opioid use and 1663 (56.7%) reported injecting drugs daily. A total of 1224 participants (41.7%) reported recent incarceration, with a median (IQR) incarceration of 15 (3-60) days in the past 6 months. Recent incarceration was associated with past-6-month overdose (adjusted odds ratio [AOR], 1.38; 95% CI, 1.12-1.70) and recent SUD treatment (AOR, 1.62; 95% CI, 1.36-1.93) but not recent medication for opioid use disorder (MOUD; AOR, 1.03; 95% CI, 0.82-1.28) or currently carrying naloxone (AOR, 1.02; 95% CI, 0.86-1.21). Conclusions and Relevance: In this cross-sectional study of PWUD in rural areas, participants commonly experienced recent incarceration, which was not associated with MOUD, an effective and lifesaving treatment. The criminal legal system should implement effective SUD treatment in rural areas, including MOUD and provision of naloxone, to fully align with evidence-based SUD health care policies.

Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus.

Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration. NCT02344290.