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BackgroundRising overdose deaths globally and increased social isolation during the coronavirus disease 2019 (COVID-19) pandemic may have disproportionately impacted people with human immunodeficiency virus (PWH) with substance use disorders (SUD). We examined trends in SUD risk among PWH before and after the COVID-19 shelter-in-place (SIP) mandate.MethodsData were collected between 2018 and 2022 among PWH enrolled across 8 US sites in the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We evaluated changes in moderate/high SUD risk after SIP using interrupted time series analyses.ResultsThere were 7126 participants, including 21 741 SUD assessments. The median age was 51 (interquartile range, 39-58) years; 12% identified as Hispanic or Latino/Latina, 46% Black/African American, and 46% White. Moderate/high SUD risk increased continuously after the pandemic's onset, with 43% (95% confidence interval [CI], 40%-46%) endorsing moderate/high SUD risk post-SIP, compared to 24% (95% CI, 22%-26%) pre-SIP (P < .001). There were increases in the use of heroin, methamphetamine, and fentanyl, and decreases in prescription opioids and sedatives post-SIP. Further, there was a decrease in reported substance use treatment post-SIP compared to pre-SIP (P = .025).ConclusionsThe rising prevalence of SUD through late 2022 could be related to an increase in isolation and reduced access to substance use and HIV treatment caused by disruptions due to COVID-19. A renewed investment in integrated substance use treatment is vital to address the combined epidemics of substance use and HIV following the COVID-19 pandemic and to support resilience in the face of future disruptions.

BackgroundEstimating 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 findingsUsing 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.ConclusionsThe 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.

BackgroundHospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD.MethodsLinear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (

Model species continue to underpin groundbreaking plant science research. At the same time, the phylogenetic resolution of the land plant Tree of Life continues to improve. The intersection of these two research paths creates a unique opportunity to further extend the usefulness of model species across larger taxonomic groups. Here we promote the utility of the Arabidopsis thaliana model species, especially the ability to connect its genetic and functional resources, to species across the entire Brassicales order. We focus on the utility of using genomics and phylogenomics to bridge the evolution and diversification of several traits across the Brassicales to the resources in Arabidopsis, thereby extending scope from a model species by establishing a model clade. These Brassicales-wide traits are discussed in the context of both the model species Arabidopsis thaliana and the family Brassicaceae. We promote the utility of such a model clade and make suggestions for building global networks to support future studies in the model order Brassicales.

ObjectiveWe describe the prevalence of COVID-19 vaccine uptake, substance use, and other factors associated with vaccine hesitancy among participants from nine North American cohort studies following a diverse group of individuals at risk for or living with HIV.MethodsBetween May 2021 and January 2022, participants completed a survey related to COVID-19 vaccination. Participants included those with and without substance use. Those responding as 'no' or 'undecided' to the question "Do you plan on getting the COVID-19 vaccine?" were categorized as vaccine hesitant. Differences between groups were evaluated using chi-square methods and multivariable log-binomial models were used to calculate prevalence ratios (PR) of COVID-19 vaccine hesitancy with separate models for each substance.ResultsAmong 1,696 participants, COVID-19 vaccination was deferred or declined by 16%. Vaccine hesitant participants were younger, with a greater proportion unstably housed (14.8% vs. 10.0%; p = 0.02), and not living with HIV (48.% vs. 36.6%; p

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.

We created a brief version of The Index, a validated patient-reported measure that has potential to quickly identify patients at risk for poor retention. We analyzed Index scores from 2406 patients from 2016 to 2017 in a national cohort of patients in human immunodeficiency virus (HIV) care. Index scores predicted poor retention 12 months after administered.

BackgroundHIV infection leads to endothelial activation, promoting platelet adhesion, and accelerating atherosclerosis. Our goal was to determine whether biomarkers of endothelial activation and hemostasis/thrombosis were elevated in people with treated HIV (PWH) before myocardial infarction (MI).MethodsIn a case-control study nested within the CFAR Network of Integrated Clinical Systems (CNICS) cohort, we compared 69 adjudicated cases with type 1 MI with 138 controls matched for antiretroviral therapy regimen. We measured angiopoietin-1, angiopoietin-2 (ANG-2), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), von Willebrand factor, C-reactive protein (CRP), interleukin-6 (IL-6), plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, and apolipoprotein A1 in stored plasma. Conditional logistic regression identified associations with subsequent MI, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores.ResultsHigher IL-6 was associated with MI after adjustment for ASCVD score (adjusted odds ratio [AOR] 1.51, 95% confidence interval [95% CI]: 1.05 to 2.17 per standard-deviation-scaled log 2 increment). In a separate model adjusting for VACS score, higher ANG-2 (AOR 1.49, 95% CI: 1.04 to 2.14), higher CRP (AOR 1.45, 95% CI: 1.06 to 2.00), and higher IL-6 (AOR 1.68, 95% CI: 1.17 to 2.41) were associated with MI. In a sensitivity analysis excluding PWH with viral load ≥400 copies/mL, higher IL-6 remained associated with MI after adjustment for ASCVD score and after adjustment for VACS score.ConclusionsAmong PWH, higher levels of plasma IL-6, CRP, and ANG-2 predict subsequent type 1 MI, independent of conventional risk scores. IL-6 had the most consistent associations with type 1 MI, regardless of viral load suppression.

In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates.

BACKGROUND: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. METHODS: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. RESULTS: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. CONCLUSIONS: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

OBJECTIVES: The relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular disease in people with HIV (PWH) is incompletely understood. We determined whether COPD is associated with risk of myocardial infarction (MI) among PWH, and if this differs for type 1 (T1MI) and type 2 (T2MI). DESIGN: We utilized data from five sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, a multisite observational study. METHODS: Our primary outcome was an adjudicated MI, classified as T1MI or T2MI. We defined COPD based on a validated algorithm requiring COPD diagnosis codes and at least 90-day continuous supply of inhalers. We conducted time-to-event analyses to first MI and used multivariable Cox proportional hazards models to measure associations between COPD and MI. RESULTS: Among 12 046 PWH, 945 had COPD. Overall, 309 PWH had an MI: 58% had T1MI ( N  = 178) and 42% T2MI ( N  = 131). In adjusted models, COPD was associated with a significantly increased risk of all MI [adjusted hazard ratio (aHR) 2.68 (95% confidence interval (CI) 1.99-3.60)] even after including self-reported smoking [aHR 2.40 (95% CI 1.76-3.26)]. COPD was also associated with significantly increased risk of T1MI and T2MI individually, and with sepsis and non-sepsis causes of T2MI. Associations were generally minimally changed adjusting for substance use. CONCLUSION: COPD is associated with a substantially increased risk for MI, including both T1MI and T2MI, among PWH. Given the association with both T1MI and T2MI, diverse mechanistic pathways are involved. Future strategies to decrease risk of T1MI and T2MI in PWH who have COPD are needed.

BackgroundThe impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown.MethodsWe defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models.ResultsWith the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73-.82), an equal risk of progressing from stage 2 to 3 (1.00; .92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants.ConclusionsThe original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

BACKGROUND: The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH. METHODS: We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations. RESULTS: We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation. CONCLUSIONS: Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population.

BackgroundThe COVID-19 pandemic has compounded the longstanding drug poisoning crisis in Canada and the United States (US). Research is needed to understand the contributions of COVID-19 and subsequent infection control measures. We sought to estimate the prevalence of and factors associated with nonfatal overdose among participants in nine prospective cohorts of people who use unregulated drugs (PWUD) in Canada and the US.MethodsData were derived from nine cohorts of PWUD in urban centres in Canada (Vancouver, BC) and the US (Baltimore, MD; Miami, FL; Chicago, IL; Los Angeles, CA) between May, 2020 and April, 2021. Multivariable logistic regression was used to identify factors associated with nonfatal overdose among participants who used unregulated drugs in the past month.ResultsAmong 885 participants (including 253 females), 41 (4.6 %) experienced a non-fatal overdose in the past month, and 453 (51.2 %) reported being highly impacted day-to-day by the pandemic. In multivariable analyses, people who experienced a non-fatal overdose were more likely to be female (Adjusted Odds Ratio [AOR]=2.18;95 % Confidence Interval [CI]=1.10-4.30); unstably housed/homeless (AOR=2.16;95 % CI=1.11-4.26); engaged in medications for opioid use disorder (AOR=2.45;95 % CI=1.19-4.97); and highly impacted day-to-day (AOR=2.42;95 % CI=1.22-5.10).ConclusionOur findings may reflect characteristics of participants who experienced a compounding of vulnerabilities during the pandemic and thus are vulnerable to overdose, including women, those unstably housed/homeless, and those who perceived their daily lives were highly impacted by the pandemic. Multi-level interventions are needed to remediate the vulnerabilities and address the main driver of poisoning crisis.

People living with (PLWH) and at risk for HIV and people who use drugs (PWUD) are at heightened risk for health consequences of COVID-19 because of compromised immunity and high comorbidities. We studied their use of COVID-19 testing during the first year of the COVID-19 pandemic. Eight NIDA funded cohorts across North America in the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) administered multiple waves of a COVID-19 survey. Respondents were at least 18 years of age, half PLWH, and many active substance users. Wave one of the COVID-19 survey was May-November, 2020 and wave two October 2020-April 2021. Associations of COVID-19 testing with demographics, socio-demographics, substance use, and HIV-status were assessed. Of the 3762 responses from 2331 individuals, half reported ever COVID-19 testing (49.1 %), with 4.3 % reporting a positive test (163/3762 surveys=4.3 %) and 41.5 % of people reporting current symptoms reported having been tested. In multivariable analysis adjusting for age, sex, and cohort type associations with COVID-19 testing included African American/Black identification compared to Caucasian/white (adjusted odds ratio (AOR)= 0.68; 95 % confidence interval (CI) 0.53, 0.88); being unemployed (AOR=0.61; 95 % CI 0.51, 0.73), and living with HIV (AOR=0.76; 95 % CI0.65, 0.90). Findings from these C3PNO COVID-19 modules suggests that in the first year of the pandemic COVID-19 testing was not broadly accessed by these marginalized populations including PLWH and those unemployed. Factors associated with not testing may also parallel those for vaccination and identify populations needing better access to COVID-19 prevention.

BackgroundThe COVID-19 pandemic disrupted the normal delivery of HIV care, altered social support networks, and caused economic insecurity. People with HIV (PWH) are vulnerable to such disruptions, particularly if they have a history of substance use. We describe engagement in care and adherence to antiretroviral therapy (ART) for PWH during the pandemic.MethodsFrom May 2020 to February 2021, 773 PWH enrolled in 6 existing cohorts completed 1495 surveys about substance use and engagement in HIV care during the COVID-19 pandemic. We described the prevalence and correlates of having missed a visit with an HIV provider in the past month and having missed a dose of ART in the past week.ResultsThirteen percent of people missed an HIV visit in the past month. Missing a visit was associated with unstable housing, food insecurity, anxiety, low resiliency, disruptions to mental health care, and substance use including cigarette smoking, hazardous alcohol use, cocaine, and cannabis use. Nineteen percent of people reported missing at least one dose of ART in the week prior to their survey. Missing a dose of ART was associated with being a man, low resiliency, disruptions to mental health care, cigarette smoking, hazardous alcohol use, cocaine, and cannabis use, and experiencing disruptions to substance use treatment.ConclusionsSocial determinants of health, substance use, and disruptions to mental health and substance use treatment were associated with poorer engagement in HIV care. Close attention to continuity of care during times of social disruption is especially critical for PWH.

BackgroundThis study examines individual-level factors associated with avoiding two important health services for people who use drugs-medications for treatment of opioid use disorder and syringe service programs-during the first year of the COVID-19 pandemic.MethodsData come from two subsamples of people who use drugs who were active participants in one of nine cohort studies in Vancouver, British Columbia; Baltimore, Maryland; Los Angeles, California; Chicago, Illinois; and Miami, Florida. Participants were interviewed remotely about COVID-19-associated disruptions to healthcare. We estimated the association of demographic, social, and health factors with each outcome using logistic regression among 702 participants (medication analysis) and 304 participants (syringe service analysis.) Analyses were repeated, stratified by city of residence, to examine geographic variation in risk.ResultsThere were large differences between cities in the prevalence of avoiding picking up medications for opioid use disorder, with almost no avoidance in Vancouver (3%) and nearly universal avoidance in Los Angeles, Chicago, and Miami (>90%). After accounting for between-city differences, no individual factors were associated with avoiding picking up medications. The only factor significantly associated with avoiding syringe service programs was higher levels of self-reported worry about COVID-19.ConclusionDuring the first year of the COVID-19 pandemic, geographic differences in service and policy contexts likely influenced avoidance of health and harm reduction services by people who use drugs in the United States and Canada more than individual differences between people.

BackgroundAlcohol use during the COVID-19 pandemic increased. People living with HIV or at risk for HIV acquisition often have psycho-social and structural barriers or co-occurring substance use making them vulnerable to the adverse effects of alcohol. We describe factors associated with alcohol use during the COVID-19 pandemic in this group.MethodsFrom May 2020 to February 2021, 1984 people enrolled in 6 existing cohort studies completed surveys about alcohol and other drug use during the COVID-19 pandemic. We describe the past-month prevalence of no alcohol use, low-risk use, and hazardous use. We use multinomial regression to describe factors associated with low-risk or hazardous alcohol use relative to no alcohol use.ResultsForty-five percent of participants reported no alcohol use, 33% low-risk use, and 22% hazardous use in the past 30 days. Cannabis and stimulant use were associated with a higher prevalence of low-risk use relative to no use. Tobacco, stimulant, cannabis use and recent overdose were associated with a higher prevalence of hazardous use relative to no use. Substance use treatment and living with HIV were associated with a lower prevalence of low-risk or hazardous use relative to no use.ConclusionsStimulant use was strongly associated with a higher prevalence of hazardous alcohol use while engagement in substance use treatment or living with HIV was associated with a lower prevalence. Ascertaining hazardous alcohol and other drug use, particularly stimulants, in clinical care could identify people at higher risk for adverse outcome and harm reduction counseling.

BackgroundPeople 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.MethodsWe 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.ResultsDuring 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.ConclusionsCurrent 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.

PurposeThe efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer.Patients and methodsPARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined.ResultsSixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group.ConclusionsClinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies.

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.

BackgroundThe updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)-specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality.MethodsBecause complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count

BackgroundUnderstanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.SettingCenters for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.MethodsWe identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores.ResultsOf 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count

ObjectivesThe epidemiology of hospitalized acute kidney injury (AKI) among people living with HIV (PLWH) in the era of modern antiretroviral therapy (ART) for all PLWH is not well characterized. We evaluated the incidence of and risk factors for hospitalized AKI from 2005 to 2015 among PLWH on ART.MethodsWe conducted a retrospective analysis of PLWH from the Johns Hopkins HIV Clinical Cohort. We defined hospitalized AKI as a rise of ≥ 0.3 mg/dL in serum creatinine (SCr) within any 48-h period or a 50% increase in SCr from baseline and assessed associations of risk factors with incident AKI using multivariate Cox regression models.ResultsMost participants (75%) were black, 34% were female, and the mean age was 43 years. The incidence of AKI fluctuated annually, peaking at 40 per 1000 person-years (PY) [95% confidence interval (CI) 22-69 per 1000 PY] in 2007, and reached a nadir of 20 per 1000 PY (95% CI 11-34 per 1000 PY) in 2010. There was no significant temporal trend (-3.3% change per year; 95% CI -8.6 to 2.3%; P = 0.24). After multivariable adjustment, characteristics independently associated with AKI included black race [hazard ratio (HR) 2.44; 95% CI 1.42-4.20], hypertension (HR 1.62; 95% CI 1.09-2.38), dipstick proteinuria > 1 (HR 1.86; 95% CI 1.07-3.23), a history of AIDS (HR 1.82; 95% CI 1.29-2.56), CD4 count

ObjectivesTo define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19.DesignObservational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020.MethodsWe calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ cell count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores.ResultsAmong 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4+ cell count less than 350 cells/μl, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4+ cell count less than 350 cells/μl (proxy for CD4+ nadir), current low CD4+ : CD8+ ratio, diabetes, and obesity.ConclusionOur results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4+ cell count or current low CD4+ : CD8+ ratio had greater risk of COVID-19.

BackgroundIndependent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada.MethodsWe examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P