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Objective To characterize and address the opioid crisis disproportionately impacting rural U.S. regions. Methods The Rural Opioid Initiative (ROI) is a two-phase project to collect and harmonize quantitative and qualitative data and develop tailored interventions to address rural opioid use. The baseline quantitative survey data from people who use drugs (PWUD) characterizes the current opioid epidemic (2018–2020) in eight geographically diverse regions. Results Among 3,084 PWUD, 92% reported ever injecting drugs, 86% reported using opioids (most often heroin) and 74% reported using methamphetamine to get high in the past 30 days; 53% experienced homelessness in the prior 6 months; and 49% had ever overdosed. Syringe service program use varied by region and 53% had ever received an overdose kit or naloxone prescription. Less than half (48%) ever received medication for opioid use disorder (MOUD). Conclusions The ROI combines data across eight rural regions to better understand drug use including drivers and potential interventions in rural areas with limited resources. Baseline ROI data demonstrate extensive overlap between opioid and methamphetamine use, high homelessness rates, inadequate access to MOUD, and other unmet needs among PWUD in the rural U.S. By combining data across studies, the ROI provides much greater statistical power to address research questions and better understand the syndemic of infectious diseases and drug use in rural settings including unmet treatment needs.

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.

Background Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. Methods We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH. Results We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI. Conclusions Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

Background Persons with human immunodeficiency virus (HIV) have higher risks for myocardial infarction (MI) than the general population. This is driven in part by higher type 2 MI (T2MI, due to coronary supply-demand mismatch) rates among persons with HIV (PWH). In the general population, T2MI has higher mortality than type 1 MI (T1MI, spontaneous and generally due to plaque rupture and thrombosis). PWH have a greater burden of comorbidities and may therefore have an even greater excess risk for complication and death in the setting of T2MI. However, mortality patterns after T1MI and T2MI in HIV are unknown. Methods We analyzed mortality after MI among PWH enrolled in the multicenter, US-based Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort ( N  = 28,186). Incident MIs occurring between January 1, 1996, and December 31, 2014, were centrally adjudicated and classified as T1MI or T2MI. We first compared mortality following T1MI vs. T2MI among PWH. Cox survival analyses and Bayesian model averaging were then used to evaluate pre-MI covariates associated with mortality following T1MI and T2MI. Results Among the 596 out of 28,186 PWH who experienced MI (2.1%; 293 T1MI and 303 T2MI), mortality rates were significantly greater after T2MI (22.2/100 person-years; 1-, 3-, and 5-year mortality 39%, 52%, and 62%) than T1MI (8.2/100 person-years; 1-, 3-, and 5-year mortality 15%, 22%, and 30%). Significant mortality predictors after T1MI were higher HIV viral load, renal dysfunction, and older age. Significant predictors of mortality after T2MI were low body-mass index (BMI) and detectable HIV viral load. Conclusions Mortality is high following MI for PWH and substantially greater after T2MI than T1MI. Predictors of death after MI differed by type of MI, reinforcing the different clinical scenarios associated with each MI type and the importance of considering MI types separately.

Background Numerous upper airway anatomy characteristics are risk factors for sleep apnea, which affects 26% of older Americans, and more severe sleep apnea is associated with cognitive impairment. This study explores the pathophysiology and links between upper airway anatomy, sleep, and cognition. Methods Participants in the Multi-Ethnic Study of Atherosclerosis underwent an upper airway MRI, polysomnography to assess sleep measures including the apnea-hypopnea index (AHI) and completed the Cognitive Abilities Screening Instrument (CASI). Two model selection techniques selected from among 67 upper airway measures those that are most strongly associated with CASI score. The associations of selected upper airway measures with AHI, AHI with CASI score, and selected upper airway anatomy measures with CASI score, both alone and after adjustment for AHI, were assessed using linear regression. Results Soft palate volume, maxillary divergence, and upper facial height were significantly positively associated with higher CASI score, indicating better cognition. The coefficients were small, with a 1 standard deviation (SD) increase in these variables being associated with a 0.83, 0.75, and 0.70 point higher CASI score, respectively. Additional adjustment for AHI very slightly attenuated these associations. Larger soft palate volume was significantly associated with higher AHI (15% higher AHI (95% CI 2%,28%) per SD). Higher AHI was marginally associated with higher CASI score (0.43 (95% CI 0.01,0.85) per AHI doubling). Conclusions Three upper airway measures were weakly but significantly associated with higher global cognitive test performance. Sleep apnea did not appear to be the mechanism through which these upper airway and cognition associations were acting. Further research on the selected upper airway measures is recommended.

Limited research has examined the possible synergistic interrelationships between serious bacterial infections (SBIs) of the heart (i.e., endocarditis), bone, spine, brain, or joints (e.g., osteomylelitis) and hepatitis C virus (HCV) infections. We examined whether syndemic interactions existed between SBI, HCV, and substance-use-related factors in rural communities, hypothesizing that injection-mediated risks elevated the likelihood for both SBIs and HCV infections, which could be exacerbated by synergistic biological-biological or biological and social interactions. We calculated the prevalence ratios (PRs) of past-year SBI associated with each risk factor in separate models. Effect modification among significant risk factors was assessed using multiplicative interaction. Among 1936 participants, 57% were male and 85% White, with a mean age of 36 years. Eighty-nine participants (5%) reported hospitalization for an SBI in the year prior to the survey. More than half tested HCV-antibody-positive (58%); 62 (5.6%) of the participants with a positive HCV antibody result reported past-year hospitalization with an SBI. Injection behaviors were correlated with other SBI risk factors, including multiple injections in the same injection event (MIPIE), injection equipment sharing, and fentanyl use. In adjusted models, MIPIE (PR: 1.79; 95% confidence interval [CI]: 1.03, 3.11) and fentanyl use (PR: 1.68; 95% CI: 1.04, 2.73) were significantly associated with past-year SBI. Our analyses pointed to co-occurring epidemics of SBI and HCV, related to the cumulative health effects of fentanyl use contributing to frequent injections and MIPIE. Both the SBI and HCV epidemics present public health challenges and merit tailored interventions.

Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Genetic architecture of cardiometabolic risks in people living with HIV [RAW_REF_TEXT] Haoxiang Cheng1 na1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Anshuman Sewda1,2 na1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Carla Marquez-Luna3, [/RAW_REF_TEXT] [RAW_REF_TEXT] Sierra R. White1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Bridget M. Whitney4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Jessica Williams-Nguyen4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Robin M. Nance1,5, [/RAW_REF_TEXT] [RAW_REF_TEXT] Won Jun Lee1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Mari M. Kitahata5,6, [/RAW_REF_TEXT] [RAW_REF_TEXT] Michael S. Saag7, [/RAW_REF_TEXT] [RAW_REF_TEXT] Amanda Willig7, [/RAW_REF_TEXT] [RAW_REF_TEXT] Joseph J. Eron8, [/RAW_REF_TEXT] [RAW_REF_TEXT] W. Christopher Mathews9, [/RAW_REF_TEXT] [RAW_REF_TEXT] Peter W. Hunt10, [/RAW_REF_TEXT] [RAW_REF_TEXT] Richard D. Moore11,12, [/RAW_REF_TEXT] [RAW_REF_TEXT] Allison Webel13, [/RAW_REF_TEXT] [RAW_REF_TEXT] Kenneth H. Mayer14, [/RAW_REF_TEXT] [RAW_REF_TEXT] Joseph A. Delaney4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Paul K. Crane5, [/RAW_REF_TEXT] [RAW_REF_TEXT] Heidi M. Crane5,6, [/RAW_REF_TEXT] [RAW_REF_TEXT] Ke Hao1 na2 & [/RAW_REF_TEXT] [RAW_REF_TEXT] Inga Peter 1 na2 [/RAW_REF_TEXT] BMC Medicine volume 19, Article number: 114 (2021) Cite this article [RAW_REF_TEXT] 102 Accesses [/RAW_REF_TEXT] [RAW_REF_TEXT] Metrics details [/RAW_REF_TEXT] The Original Article was published on 28 October 2020 Correction to: BMC Med 18, 288 (2020) https://doi.org/10.1186/s12916-020-01762-z The original article [1] contained an error whereby first author, Haoxiang Cheng’s name was displayed incorrectly. Genetic architecture of cardiometabolic risks in people living with HIV [RAW_REF_TEXT] Haoxiang Cheng1 na1, Anshuman Sewda1,2 na1, Carla Marquez-Luna3, Sierra R. White1, Bridget M. Whitney4, Jessica Williams-Nguyen4, Robin M. Nance1,5, Won Jun Lee1, Mari M. Kitahata5,6, Michael S. Saag7, Amanda Willig7, Joseph J. Eron8, W. Christopher Mathews9, Peter W. Hunt10, Richard D. Moore11,12, Allison Webel13, Kenneth H. Mayer14, Joseph A. Delaney4, Paul K. Crane5, Heidi M. Crane5,6, Ke Hao1 na2 & Inga Peter 1 na2 [/RAW_REF_TEXT] BMC Medicine volume 19, Article number: 114 (2021) Cite this article [RAW_REF_TEXT] 102 Accesses Metrics details

ObjectiveAnaemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era.DesignRetrospective cohort study.SettingUSA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018.Participants16 505 PLWH were included in this study.Main outcome measuresAnaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change.ResultsDuring a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use.ConclusionThese findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

Background Self-reported antiretroviral therapy (ART) adherence measures that are associated with plasma viral load (VL) are valuable to clinicians and researchers, but are rarely examined among groups vulnerable to dropping out of care. One-seventh of all those living with HIV pass through incarceration annually and criminal-justice (CJ) involved people living with HIV (PLH) are vulnerable to falling out of care. We examined the association of self-reported ART adherence with VL in a criminal-justice sample compared to a routine-care sample. Methods Samples: We examined data from a multisite collaboration of studies addressing the continuum of HIV care among CjJ involved persons in the Seek, Test, Treat, and Retain cohort. Data pooled from seven CJ- studies ( n  = 414) were examined and compared with the routine-care sample from the Centers for AIDS Research Network of Integrated Clinical Systems’ seven sites ( n  = 11,698). Measures: In both samples, data on self-reported percent ART doses taken were collected via the visual analogue scale adherence measure. Viral load data were obtained by blood-draw. Analysis: We examined the associations of adherence with VL in both cohorts using mixed effects linear regression of log-VL, and mixed effects logistic regression of binary VL (≥ 200 copies/mL) outcomes. Interactions by CD4 count and self-reported health status were also tested. Results Among the CJ sample, the coefficient for log-VL was − 0.31 (95% CI = − 0.43, − 0.18; P  < 0.01) and that in the routine-care sample was − 0.42 (95% CI = − 0.45, − 0.38; P  < 0.01). For the logistic regression of binary detectable VL on 10% increments of adherence we found the coefficient was − 0.26 (95% CI = − 0.37, − 0.14; P  < 0.01) and in the routine-care sample it was − 0.38 (95% CI = − 0.41, − 0.35; P  < 0.01). There was no significant interaction by CD4 count level in the CJ sample, but there was in the routine-care sample. Conversely, there was a significant interaction by self-reported health status level in the criminal-justice sample, but not in the routine-care sample. Conclusions The visual analogue scale is valid and useful to measure ART adherence, supporting treatment for CJ- involved PLH vulnerable to falling out of care. Research should examine adherence and VL in additional populations.

Background Information regarding the impact of substance use on the timing of entry into HIV care is lacking. Better understanding of this relationship can help guide approaches and policies to improve HIV testing and linkage. Methods We examined the effect of specific substances on stage of HIV disease at entry into care in over 5000 persons with HIV (PWH) newly enrolling in care. Substance use was obtained from the AUDIT-C and ASSIST instruments. We examined the association between early entry into care and substance use (high-risk alcohol, methamphetamine, cocaine/crack, illicit opioids, marijuana) using logistic and relative risk regression models adjusting for demographic factors, mental health symptoms and diagnoses, and clinical site. Results We found that current methamphetamine use, past and current cocaine and marijuana use was associated with earlier entry into care compared with individuals who reported no use of these substances. Conclusion Early entry into care among those with substance use suggests that HIV testing may be differentially offered to people with known HIV risk factors, and that individuals with substances use disorders may be more likely to be tested and linked to care due to increased interactions with the healthcare system.