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Background Using the results of a site assessment survey performed at clinics throughout Washington, DC, we studied the impact of clinic-level factors on antiretroviral therapy (ART) initiation and viral suppression (VS) among people living with human immunodeficiency virus (HIV; PLWH). Methods This was a retrospective analysis from the District of Columbia (DC) Cohort, an observational, clinical cohort of PLWH from 2011–2018. We included data from PLWH not on ART and not virally suppressed at enrollment. Outcomes were ART initiation and VS (HIV RNA < 200 copies/mL). A clinic survey captured information on care delivery (eg, clinical services, adherence services, patient monitoring services) and clinic characteristics (eg, types of providers, availability of evenings/weekends sessions). Multivariate marginal Cox regression models were generated to identify those factors associated with the time to ART initiation and VS. Results Multiple clinic-level factors were associated with ART initiation, including retention in care monitoring and medication dispensing reviews (adjusted hazard ratios [aHRs], 1.34 to 1.40; P values < .05 for both). Furthermore, multiple factors were associated with VS, including retention in HIV care monitoring, medication dispensing reviews, and the presence of a peer interventionist (aHRs, 1.35 to 1.72; P values < .05 for all). In multivariable models evaluating different combinations of clinic-level factors, enhanced adherence services (aHR, 1.37; 95% confidence interval [CI], 1.18–1.58), medication dispensing reviews (aHR, 1.22; 95% CI, 1.10–1.36), and the availability of opioid treatment (aHR, 1.26; 95% CI, 1.01–1.57) were all associated with the time to VS. Conclusions The observed association between clinic-level factors and ART initiation/VS suggests that the presence of specific clinic services may facilitate the achievement of HIV treatment goals.

BACKGROUND Privacy-protecting analytic approaches without centralized pooling of individual-level data, such as distributed regression, are particularly important for vulnerable populations, such as children, but these methods have not yet been tested in multi-center pediatric studies. METHODS Using the electronic health data from 34 healthcare institutions in the National Patient-Centered Clinical Research Network (PCORnet), we fit 12 multivariable-adjusted linear regression models to assess the associations of antibiotic use

OBJECTIVE To examine racial/ethnic disparities in the prevalence of diabetes and prediabetes by BMI category. RESEARCH DESIGN AND METHODS In a consortium of three U.S. integrated health care systems, 4,906,238 individuals aged ≥20 years during 2012–2013 were included. Diabetes and prediabetes were ascertained by diagnosis and laboratory results; antihyperglycemic medications were also included for diabetes ascertainment. RESULTS The age-standardized diabetes and prediabetes prevalence estimates were 15.9% and 33.4%, respectively. Diabetes but not prediabetes prevalence increased across BMI categories among all racial/ethnic groups (P for trend < 0.001). Racial/ethnic minorities reached a given diabetes prevalence at lower BMIs than whites; Hawaiians/Pacific Islanders and Asians had a diabetes prevalence of 24.6% (95% CI 24.1–25.2%) in overweight and 26.5% (26.3–26.8%) in obese class 1, whereas whites had a prevalence of 23.7% (23.5–23.8%) in obese class 2. The age-standardized prediabetes prevalence estimates in overweight among Hispanics (35.6% [35.4–35.7%]), Asians (38.1% [38.0–38.3%]), and Hawaiians/Pacific Islanders (37.5% [36.9–38.2%]) were similar to those in obese class 4 among whites (35.3% [34.5–36.0%]), blacks (36.8% [35.5–38.2%]), and American Indians/Alaskan Natives (34.2% [29.6–38.8%]). In adjusted models, the strength of association between BMI and diabetes was highest among whites (relative risk comparing obese class 4 with normal weight 7.64 [95% CI 7.50–7.79]) and lowest among blacks (3.16 [3.05–3.27]). The association between BMI and prediabetes was less pronounced. CONCLUSIONS Racial/ethnic minorities had a higher burden of diabetes and prediabetes at lower BMIs than whites, suggesting the role of factors other than obesity in racial/ethnic disparities in diabetes and prediabetes risk and highlighting the need for tailored screening and prevention strategies.

Background Problematic use of alcohol and other drugs (AOD) is highly prevalent among people living with the human immunodeficiency virus (PLWH), and untreated AOD use disorders have particularly detrimental effects on human immunodeficiency virus (HIV) outcomes. The Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement are important benchmarks for access to AOD use disorder treatment. To inform improved patient care, we compared HEDIS measures of AOD use disorder treatment initiation and engagement and health care utilization among PLWH and patients without an HIV diagnosis. Methods Patients with a new AOD use disorder diagnosis documented between October 1, 2014, and August 15, 2015, were identified using electronic health records (EHR) and insurance claims data from 7 health care systems in the United States. Demographic characteristics, clinical diagnoses, and health care utilization data were also obtained. AOD use disorder treatment initiation and engagement rates were calculated using HEDIS measure criteria. Factors associated with treatment initiation and engagement were examined using multivariable logistic regression models. Results There were 469 PLWH (93% male) and 86,096 patients without an HIV diagnosis (60% male) in the study cohort. AOD use disorder treatment initiation was similar in PLWH and patients without an HIV diagnosis (10% vs. 11%, respectively). Among those who initiated treatment, few engaged in treatment in both groups (9% PLWH vs. 12% patients without an HIV diagnosis). In multivariable analysis, HIV status was not significantly associated with either AOD use disorder treatment initiation or engagement. Conclusions AOD use disorder treatment initiation and engagement rates were low in both PLWH and patients without an HIV diagnosis. Future studies need to focus on developing strategies to efficiently integrate AOD use disorder treatment with medical care for HIV.

Unhealthy alcohol use has adverse effects on HIV treatment. Screening, brief intervention, and referral to treatment (SBIRT) has some evidence of efficacy but may not be sufficient for those with low motivation or comorbid substance use. To examine the effectiveness of motivational interviewing (MI) and emailed feedback (EF) among primary care HIV-positive patients, compared with treatment as usual care (UC) only, which included SBIRT. Randomized clinical trial. Six hundred fourteen adult HIV-positive patients in Kaiser Permanente Northern California who reported prior-year unhealthy alcohol use. Participants were randomized to either three sessions of MI (one in person and two by phone), information regarding alcohol risks via EF through a patient portal, or UC alone. MI and EF participants who reported unhealthy alcohol use at 6 months were offered additional MI and EF treatment, respectively. Participant-reported unhealthy alcohol use (defined as ≥ 4/≥ 5 drinks per day for women/men), alcohol problems at 12 months, based on blinded telephone interviews. Secondary outcomes included drug use and antiretroviral (ART) adherence. At 12 months, there were no overall group differences, but in all three arms, there were declines in unhealthy alcohol use and alcohol-related problems (p

Introduction Prior studies found renal disease was common among HIV-infected outpatients. We updated incident renal disease estimates in this population, comparing those with and without tenofovir exposure. Methods We conducted a retrospective analysis of the DC Cohort, a longitudinal study of HIV patients in Washington, DC, from 2011 to 2015. We included adults prescribed antiretroviral therapy (ART) with baseline glomerular filtration rate (GFR) ≥15 ml/min per 1.73 m2. We defined renal disease as 50% decrease in GFR or doubled serum creatinine (Cr) within 3 months. We defined cumulative viral load as area under the curve (AUC) of log10 transformed longitudinal HIV RNA viral load (VL). Correlates of time to incident renal disease were identified using Cox proportional hazard regression models, adjusted for demographics and known risk factors for kidney disease. Results Among 6068 adults, 77% were Black and median age was 48 years. Incident renal disease rate was 0.77 per 100 person-years (95% confidence interval [CI]: 0.65–0.9). Factors associated with renal disease were age (adjusted hazard ratio [aHR]: 1.4; CI 1.1–1.7 per 10 years), public non-Medicaid, non-Medicare insurance (aHR: 3.4; CI: 1.9–6.4), AUC VL (aHR: 1.1; CI: 1.1–1.2), diabetes mellitus (aHR: 1.6; CI: 1.0–2.4), and mildly reduced GFR (60–89 ml/min per 1.73 m2) (aHR: 1.5; CI: 1.0–2.3); recent tenofovir exposure was not associated with renal disease (aHR: 0.7; CI: 0.5–1.1). Conclusion Our study revealed a substantial burden of renal disease among HIV patients. Cumulative VL was associated with renal disease, suggesting that early VL suppression may decrease its incidence., Graphical abstract

BACKGROUND: Use of electronic health records (EHRs) in health research may lead to the false assumption of complete event ascertainment. We present a systematic approach to estimate “observation windows” (OWs), defined as time periods within which the assumption of complete ascertainment of events is more likely to hold, as a quality control approach to reducing the likelihood of this false assumption. We demonstrate the impact of observation windows on estimating the rates of type 2 diabetes mellitus (diabetes) using EHR diagnosis, medication, and laboratory data from HIV clinical cohorts. METHODS: Data contributed by 16 HIV clinical cohorts to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were used to identify and evaluate OWs for an operationalized definition of diabetes occurrence as a case study. Procedures included: 1) gathering cohort-level data; 2) visualizing and summarizing gaps in observations; 3) systematically establishing start and stop dates during which complete ascertainment of diabetes events was reasonable; and 4) visualizing the diabetes OWs relative to the cohort open and close dates to identify periods of time during which immortal person time was accumulated and events were not fully ascertained. We estimated diabetes occurrence event rates and 95% confidence intervals ([,]) in the most recent decade that data were available (Jan 1, 2007 to Dec 31, 2016). RESULTS: The number of diabetes events decreased by 17% with the use of the diabetes OWs; immortal person-time was removed decreasing total person-years by 23%. Consequently, the diabetes rate increased from 1.23 (95% confidence interval [1.20, 1.25]) per 100 person-years to 1.32 ([1.29, 1.35] per 100 person-years with the use of diabetes OWs. CONCLUSIONS: As the use of EHR-curated data for event-driven health research continues to expand, OWs have utility as a quality control approach to complete event ascertainment, helping to improve accuracy of estimates by removing immortal person-time when ascertainment is incomplete.

OBJECTIVE The aim of this work was to study weight loss and risk of cardiovascular disease (CVD) or death associated with longer-term phentermine use. METHODS Using electronic health record data, 13,972 adults were identified with a first phentermine fill in 2010 to 2015, creating exposure categories according to a patient's duration of use (referent: ≤ 3 months). Multivariable linear models were used to compare percent weight loss across categories at 6, 12, and 24 months, and Cox proportional hazards models were used to compare risk of composite CVD or death, up to 3 years after starting phentermine. RESULTS The cohort was 84% female and 45% white, with a mean (SD) baseline age 43.5 (10.7) years and BMI of 37.8 (7.2) kg/m2 . In multivariable models, longer-term users of phentermine experienced more weight loss; patients using continuously for > 12 months lost 7.4% more than the referent group at 24 months (P

Background To date, there are no standardized, well-accepted, quality metrics that guide care for adults with sickle cell disease (SCD). The primary objective of this study was to evaluate the quality metrics that are in use at the Adult Sickle Cell Disease Program at Johns Hopkins Hospital (JHH) and the applicability of the metrics to Kaiser Permanente Mid-Atlantic States (KPMAS), an integrated healthcare system with a developing adult sickle cell disease program. Methods We performed a retrospective cross-sectional study of 146 KPMAS and 308 JHH patients from January 1, 2014–December 31, 2015. Demographics, genotype and data on several key quality metrics (yearly screening labs, documented vaccinations and appropriate hydroxyurea prescriptions) were collected from electronic health records (EPIC Systems). We defined hydroxyurea adherence as having had at least 6 months of refills prescribed during the two years of study by either EHR or patient report. Results Patients at KPMAS were older than those at JHH (median age 44 and 33 respectively) and less likely to have hemoglobin SS disease (29% and 66% respectively). Among KPMAS patients, 85% had documentation of any pneumococcal vaccination compared to 87% at JHH. 21 of 54 eligible patients at KPMAS and 95 of 165 eligible patients at JHH were prescribed hydroxyurea. At both institutions, 62% of patients were adherent to hydroxyurea. There were limitations to diagnosis coding and availability of vaccination and refill documentation. Conclusions Interventions to improve preventative care adherence are needed to improve outcomes in both academic medical centers and integrated health systems.

ImportanceBariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups.ObjectiveTo compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study.Design, Setting, and ParticipantsThis was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022.ExposureRYGB or SG.OutcomesPercentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery.ResultsA total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, −7.6%; 95% CI, −8.0 to −7.1; P < .001; Hispanic, −6.2%; 95% CI, −6.6 to −5.9; P < .001; White, −5.9%; 95% CI, −6.3 to −5.7; P < .001; difference in change in year 5 HbA1c level: Black, −0.29; 95% CI, −0.51 to −0.08; P = .009; Hispanic, −0.45; 95% CI, −0.61 to −0.29; P < .001; and White, −0.25; 95% CI, −0.40 to −0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P < .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P < .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse.Conclusions and RelevanceVariability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients.

Integrase inhibitors (INSTIs) are recommended by expert panels as initial therapy for people with HIV. Because there can be disparities in prescribing and uptake of novel and/or recommended therapies, this analysis assessed potential INSTI prescribing disparities using a combined data set from the Johns Hopkins HIV Clinical Cohort and the DC Cohort. We performed multivariable logistic regression to identify factors associated with ever being prescribed an INSTI. Disparities were noted, including clinic location, age, and being transgender. Identifying disparities may allow clinicians to focus their attention on these individuals and ensure that therapy decisions are grounded in valid clinical reasons., We assessed INSTI prescribing disparities using Johns Hopkins HIV Clinical Cohort/DC Cohort data. Disparities were noted, including clinic location, age, and being transgender. Clinicians should focus their attention on these individuals and make therapy decisions grounded in valid clinical reasons.

BackgroundIndependent of CD4 cell count, 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 USA and Canada.MethodsWe examined all cancer-free PWH with one or more CD4/CD8 values from NA-ACCORD observational cohorts with validated cancer diagnoses between 1998-2016. 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/ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83,893 PWH, there were 5,628 incident cancers, including lung cancer (n=755), Kaposi sarcoma (KS, n=501), non-Hodgkin lymphoma (NHL, n=497), and anal cancer (n=439). Median age at cohort entry was 43 years, 87% were male, and 43% were white. Overall median six-month lagged CD4/CD8 ratio was 0.52 (interquartile range: 0.30-0.82). Compared with six-month lagged CD4/CD8=0.80, CD4/CD8=0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval: 1.14-1.35]). CD4/CD8 ratio was also inversely associated with NHL, KS, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all pConclusionsLow CD4/CD8 ratio up to 24 months prior to cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Background The 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. Methods Because 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 Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Background Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). Methods We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. Results Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5). Conclusions Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

BACKGROUND: Chronic hepatitis B (HBV) is the predominant cause of hepatocellular carcinoma (HCC) worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multi-cohort study of HIV/HBV-coinfected individuals. METHODS & RESULTS: We included HIV/HBV-coinfected persons within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995–2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted hazard (aHRs [95% confidence intervals]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, hepatitis C), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 HIV/HBV-coinfected individuals (median age, 43 years; 93% male; 52.4% non-white), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5–2.1] events/1,000 person-years). Risk factors for HCC included age 40–49 years (aHR, 1.97 [1.22–3.17]), age ≥50 years (aHR, 2.55 [1.49–4.35]), hepatitis C coinfection (aHR, 1.61 [1.07–2.40]), and heavy alcohol use (aHR, 1.52 [1.04–2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56–1.43]) and time-updated CD4+ percentage 200 IU/mL (aHR, 2.22 [1.42–3.47]) and was higher with each 1.0 log(10) IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05–1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24–0.73]). CONCLUSION: HIV/HBV-coinfected individuals on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.

Objective To construct and publicly release a set of medical concept embeddings for codes following the ICD-10 coding standard which explicitly incorporate hierarchical information from medical codes into the embedding formulation. Materials and Methods We trained concept embeddings using several new extensions to the Word2Vec algorithm using a dataset of approximately 600,000 patients from a major integrated healthcare organization in the Mid-Atlantic US. Our concept embeddings included additional entities to account for the medical categories assigned to codes by the Clinical Classification Software Revised (CCSR) dataset. We compare these results to sets of publicly released pretrained embeddings and alternative training methodologies. Results We found that Word2Vec models which included hierarchical data outperformed ordinary Word2Vec alternatives on tasks which compared naïve clusters to canonical ones provided by CCSR. Our Skip-Gram model with both codes and categories achieved 61.4% normalized mutual information with canonical labels in comparison to 57.5% with traditional Skip-Gram. In models operating on two different outcomes, we found that including hierarchical embedding data improved classification performance 96.2% of the time. When controlling for all other variables, we found that co-training embeddings improved classification performance 66.7% of the time. We found that all models outperformed our competitive benchmarks. Discussion We found significant evidence that our proposed algorithms can express the hierarchical structure of medical codes more fully than ordinary Word2Vec models, and that this improvement carries forward into classification tasks. As part of this publication, we have released several sets of pretrained medical concept embeddings using the ICD-10 standard which significantly outperform other well-known pretrained vectors on our tested outcomes.

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence (RWE) in the evaluation of new treatments or products. RWE studies often rely on real-world data (RWD), including data extracted from healthcare records or data captured by mobile phones or other consumer devices. Global assessments of RWD sources are not helpful in assessing whether any specific RWD element is fit for any specific purpose. Instead, evidence generators and evidence consumers should clearly identify the specific health state or clinical phenomenon of interest and then consider each step between that clinical phenomenon and its representation in a research database. We propose specific questions regarding potential error or bias affecting each of those steps: Would a person experiencing this clinical phenomenon present for care in this setting or interact with this recording device? Would this clinical phenomenon be accurately recognized or assessed? How might the recording environment or tools affect accurate and consistent recording of this clinical phenomenon? Can data elements from different sources be harmonized, both technically (same format) and semantically (same meaning)? Can the original data elements be consistently reduced to a useful clinical phenotype? Addressing these questions requires a range of clinical, organizational, and technical expertise. Transparency regarding each step in the creation of RWD is essential if evidence consumers are to rely on RWE studies.

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence in the evaluation of new treatments or products. Real-world clinical trials or pragmatic trials often differ from traditional clinical trials in the use of open-label or nonblinded treatments delivered by real-world clinicians in community practice settings. Blinding and standardization of treatment may sometimes be necessary for internal validity, but they may also obscure or distort meaningful differences between treatments. When investigators consider whether blinding of clinicians, patients, or assessors is necessary, we suggest they consider several specific questions: Will clinicians, patients, and assessors have expectations or preferences regarding benefits or adverse effects? How might those expectations affect treatment uptake, treatment adherence, or assessment of outcomes? Will expectations differ in the settings where trial results will be applied? How would blinding of treatment reduce biases? How would blinding obscure true differences between treatments? How would procedures necessary for blinding reduce acceptability or increase risk of trial participation? When investigators consider how strictly treatments should be standardized, we suggest they consider several specific questions: How would treatment effectiveness or safety vary according to clinician experience or expertise? What level of experience or expertise is available in potential trial settings and settings where trial results would be applied? Is some level of standardization necessary for valid inference? Considering any special vulnerabilities of the study population, is some level of standardization necessary to assure participant safety?

IntroductionSmoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination.MethodsParticipants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (ResultsThe overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03−2.48]), not retained (OR = 1.30 [95 % CI 1.13−1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60−2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40−5.71]), although the interaction did not reach significance (p = 0.18).ConclusionsIn this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes.

Substance use disorders (SUDs) are common among people with HIV and can prevent achievement of optimal health outcomes. Using data from a longitudinal HIV cohort study in the District of Columbia (2011-2018), we calculated the prevalence and correlates of SUD (alcohol, stimulant, and/or opioid use disorders) and determined the association of SUD with engagement in HIV care, ART prescription, viral suppression, and mortality. Of 8420 adults, 3168 (37.6%) had a history of any SUD, most commonly history of alcohol use disorder (29.6%). SUDs disproportionately affected Black individuals (aOR 1.33) and heterosexuals (aOR 1.18), and women had a lower risk of SUD (aOR 0.65). SUD was not associated with engagement in care, ART prescription, or viral suppression. SUD was associated with mortality (aHR 1.31). Addressing alcohol use disorder and preventable causes of death among people with HIV and substance use disorders should be priorities for clinical care and public health.Los trastornos por uso de sustancias (TUS) son comunes entre las personas con VIH y pueden impedir el logro de resultados óptimos de salud. Utilizando datos de un estudio sobre VIH de cohorte longitudinal en el Distrito de Columbia (2011–2018), calculamos la prevalencia y los correlatos de TUS (trastornos por consumo de alcohol, estimulantes y/o opioides) y determinamos la asociación de los TUS con la vinculación a cuidado de VIH, prescripción de terapia antirretroviral, supresión viral y mortalidad. De 8420 adultos, 3168 (37.6%) tenían historial de algún TUS, más comúnmente historial de trastorno por consumo de alcohol (29.6%). Los TUS afectaron de manera desproporcionada a las personas negras (aOR 1.33) y a los heterosexuales (aOR 1.18) y las mujeres tenían un riesgo menor de TUS (aOR 0.65). TUS no tuvo asociación estadísticamente significativa con la vinculación a cuidado de VIH, la prescripción de terapia antirretroviral o la supresión viral. TUS se asoció con mortalidad (aHR 1.31). Abordar el trastorno por consumo de alcohol y las causas prevenibles de muerte entre personas con VIH y trastornos por consumo de sustancias debe ser una prioridad para el cuidado clínico y la salud pública.

Recommendations for additional doses of COVID-19 vaccines for people with HIV (PWH) are restricted to those with advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk after vaccination among PWH is essential for informing vaccination guidelines.To estimate the rate and risk of breakthrough infections among fully vaccinated PWH and people without HIV (PWoH) in the United States.This cohort study used the Corona-Infectious-Virus Epidemiology Team (CIVET)-II (of the North American AIDS Cohort Collaboration on Research and Design [NA-ACCORD], which is part of the International Epidemiology Databases to Evaluate AIDS [IeDEA]), collaboration of 4 prospective, electronic health record-based cohorts from integrated health systems and academic health centers. Adult PWH who were fully vaccinated prior to June 30, 2021, were matched with PWoH on date of full vaccination, age, race and ethnicity, and sex and followed up through December 31, 2021.HIV infection.COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after a patient was fully vaccinated.Among 113 994 patients (33 029 PWH and 80 965 PWoH), most were 55 years or older (80 017 [70%]) and male (104 967 [92%]); 47 098 (41%) were non-Hispanic Black, and 43 218 (38%) were non-Hispanic White. The rate of breakthrough infections was higher in PWH vs PWoH (55 [95% CI, 52-58] cases per 1000 person-years vs 43 [95% CI, 42-45] cases per 1000 person-years). Cumulative incidence of breakthroughs 9 months after full vaccination was low (3.8% [95% CI, 3.7%-3.9%]), albeit higher in PWH vs PWoH (4.4% vs 3.5%; log-rank P .001; risk difference, 0.9% [95% CI, 0.6%-1.2%]) and within each vaccine type. Breakthrough infection risk was 28% higher in PWH vs PWoH (adjusted hazard ratio, 1.28 [95% CI, 1.19-1.37]). Among PWH, younger age (45 y vs 45-54 y), history of COVID-19, and not receiving an additional dose (aHR, 0.71 [95% CI, 0.58-0.88]) were associated with increased risk of breakthrough infections. There was no association of breakthrough with HIV viral load suppression, but high CD4 count (ie, ≥500 cells/mm3) was associated with fewer breakthroughs among PWH.In this study, COVID-19 vaccination, especially with an additional dose, was effective against infection with SARS-CoV-2 strains circulating through December 31, 2021. PWH had an increased risk of breakthrough infections compared with PWoH. Expansion of recommendations for additional vaccine doses to all PWH should be considered.

Patients who use cannabis for medical reasons may benefit from discussions with clinicians about health risks of cannabis and evidence-based treatment alternatives. However, little is known about the prevalence of medical cannabis use in primary care and how often it is documented in patient electronic health records (EHR).To estimate the primary care prevalence of medical cannabis use according to confidential patient survey and to compare the prevalence of medical cannabis use documented in the EHR with patient report.This study is a cross-sectional survey performed in a large health system that conducts routine cannabis screening in Washington state where medical and nonmedical cannabis use are legal. Among 108 950 patients who completed routine cannabis screening (between March 28, 2019, and September 12, 2019), 5000 were randomly selected for a confidential survey about cannabis use, using stratified random sampling for frequency of past-year use and patient race and ethnicity. Data were analyzed from November 2020 to December 2021.Survey measures of patient-reported past-year cannabis use, medical cannabis use (ie, explicit medical use), and any health reason(s) for use (ie, implicit medical use).Survey data were linked to EHR data in the year before screening. EHR measures included documentation of explicit and/or implicit medical cannabis use. Analyses estimated the primary care prevalence of cannabis use and compared EHR-documented with patient-reported medical cannabis use, accounting for stratified sampling and nonresponse.Overall, 1688 patients responded to the survey (34% response rate; mean [SD] age, 50.7 [17.5] years; 861 female [56%], 1184 White [74%], 1514 non-Hispanic [97%], and 1059 commercially insured [65%]). The primary care prevalence of any past-year patient-reported cannabis use on the survey was 38.8% (95% CI, 31.9%-46.1%), whereas the prevalence of explicit and implicit medical use were 26.5% (95% CI, 21.6%-31.3%) and 35.1% (95% CI, 29.3%-40.8%), respectively. The prevalence of EHR-documented medical cannabis use was 4.8% (95% CI, 3.45%-6.2%). Compared with patient-reported explicit medical use, the sensitivity and specificity of EHR-documented medical cannabis use were 10.0% (95% CI, 4.4%-15.6%) and 97.1% (95% CI, 94.4%-99.8%), respectively.These findings suggest that medical cannabis use is common among primary care patients in a state with legal use, and most use is not documented in the EHR. Patient report of health reasons for cannabis use identifies more medical use compared with explicit questions about medical use.

Objectives Delays in sepsis diagnosis can increase morbidity and mortality. Previously, we performed a Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) “look-back” analysis to identify symptoms at risk for delayed sepsis diagnosis. We found treat-and-release emergency department (ED) encounters for fluid and electrolyte disorders (FED) and altered mental status (AMS) were associated with downstream sepsis hospitalizations. In this “look-forward” analysis, we measure the potential misdiagnosis-related harm rate for sepsis among patients with these symptoms. Methods Retrospective cohort study using electronic health record and claims data from Kaiser Permanente Mid-Atlantic States (2013–2018). Patients ≥18 years with ≥1 treat-and-release ED encounter for FED or AMS were included. Observed greater than expected sepsis hospitalizations within 30 days of ED treat-and-release encounters were considered potential misdiagnosis-related harms. Temporal analyses were employed to differentiate case and comparison (superficial injury/contusion ED encounters) cohorts. Results There were 4,549 treat-and-release ED encounters for FED or AMS, 26 associated with a sepsis hospitalization in the next 30 days. The observed (0.57%) minus expected (0.13%) harm rate was 0.44% (absolute) and 4.5-fold increased over expected (relative). There was a spike in sepsis hospitalizations in the week following FED/AMS ED visits. There were fewer sepsis hospitalizations and no spike in admissions in the week following superficial injury/contusion ED visits. Potentially misdiagnosed patients were older and more medically complex. Conclusions Potential misdiagnosis-related harms from sepsis are infrequent but measurable using SPADE. This look-forward analysis validated our previous look-back study, demonstrating the SPADE approach can be used to study infectious disease syndromes.

From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/μL, and CD4 count at ART prescription increased from 160 to 364 cells/μL.

Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a near expected life span, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the life span. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive evidence-based HIV primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and noncommunicable diseases arise, providing comprehensive healthcare for persons with HIV becomes increasingly complex, including management of multiple comorbidities and the associated challenges of polypharmacy, while not neglecting HIV-related health concerns. Clinicians must address issues specific to persons of childbearing potential, including care during preconception and pregnancy, and to children, adolescents, and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America updates previous 2013 primary care guidelines.

Background Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. Methods In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005–2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2–5) and long-term (years 6–11) suppression and lowest presuppression CD4 count Results The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% white. Among patients with lowest presuppression CD4 count 500 cells/μL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01–2.06), and 1.67 (95% CI, 1.03–2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351–500 vs >500 cells/μL had an aIRR of 1.22 (95% CI, .93–1.60) during early suppression and 2.09 (95% CI, 1.18–3.70) during long-term suppression. Conclusions Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies.

Background Integrase strand transfer inhibitor (InSTI)–based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. Methods We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death. Results Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, −2.7% to 3.3%) and a HR of 1.08 (.97–1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (−3.0% to 3.7%) and a HR of 1.09 (.96–1.25). Conclusions InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.

BACKGROUND: Optimal management of noncommunicable diseases, including diabetes mellitus (DM), is crucially important as people with HIV (PWH) live longer with antiretroviral therapy. Our objective was to assess patient-level and clinic-level factors associated with achieving hemoglobin A1c (HbA1c) ≤7.0% among PWH and DM. SETTING: The DC Cohort, an observational clinical cohort of PWH, followed from 2011 to 2019 at 12 sites in Washington, DC. METHODS: Among PWH with diagnosed DM and elevated HbA1c (>7.0%), we examined the association between achieving HbA1c ≤7.0% and demographic and clinical factors, including time-updated medication data, and clinic-level factors related to services and structure. A multilevel marginal extended Cox regression model was generated to identify factors associated with time to HbA1c ≤7.0%. RESULTS: Over half (52.3%) of 419 participants achieved HbA1c ≤7.0%. Individual-level factors associated with HbA1c ≤7.0% included a diagnosis of DM after enrollment and a longer time since HIV diagnosis [hazard ratio (HR) = 2.65 and 1.13, P < 0.05 for both]. Attending a clinic with an endocrinologist was associated with the outcome [adjusted HR (aHR) = 1.41 95% confidence interval (CI): (1.01 to 1.97)]. In addition, comparing clinics that treat everyone, refer everyone or have a mix of treating and referring, showed an association between attending a clinic that treats everyone [aHR = 1.52 95% CI: (1.21 to 1.90)] or a clinic that refers everyone [aHR = 2.24 95% CI: (1.63 to 3.07)] compared with clinics with a mix in achieving glycemic control. CONCLUSION: Multiple factors are associated with achieving glycemic control in an urban cohort of PWH. Determining if specific services or structures improve DM outcomes may improve health outcomes for PWH and DM.

Background Integrase strand transfer inhibitor (INSTI)–based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). Methods cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)–, or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. Results Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92–1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07–1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06–1.91]) vs NNRTI initiators. The INSTI–DM association was attenuated (HR, 1.03 [95% CI, .71–1.49] vs NNRTIs) when accounting for 12-month weight. Conclusions Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.

In a sample of people with HIV (PWH) enrolled in an alcohol intervention trial and followed for 12months, we examined the association of changes in days (i.e., decrease, increase, no change [reference]) of unhealthy drinking (consuming ≥ 4/≥ 5 drinks for women/men) with antiretroviral therapy adherence (≥ 95% adherent), viral suppression (HIV RNA

Background Persons with HIV (PWH) are more likely to smoke and are more susceptible to the harmful effects of smoking than persons without HIV. We examined smoking patterns and use of cessation treatment among PWH and persons without HIV in a U.S. integrated health system. Methods We identified adults (≥18 years) with HIV and demographically-matched persons without HIV between July 2013 and December 2017. Smoking status and cessation treatment were ascertained from health records. We calculated age-standardized annual prevalence of smoking and evaluated trends using Cochran-Armitage tests and Poisson regression. Factors associated with cessation treatment during the study period, and smoking in the last year of the study, were evaluated by HIV status using multivariable Poisson models. Results The study included 11,235 PWH and 227,320 persons without HIV. Smoking prevalence was higher among PWH across all years but declined for both groups (from 16.6% to 14.6% in PWH and 11.6% to 10.5% in persons without HIV). Among smokers, PWH were more likely to initiate cessation treatment compared to persons without HIV (17.9% vs. 13.3%, covariate-adjusted prevalence ratio of 1.31, 95% CI = 1.15–1.50), with few differences in cessation treatment across subgroups of PWH. In 2017, smoking prevalence remained higher in PWH, especially among those who were younger or who had diagnoses of depression or substance use disorder. Conclusion In a setting with access to cessation resources, smoking prevalence decreased both in PWH and persons without HIV. PWH had greater uptake of cessation treatment, which is encouraging for smoking reduction and improved health.

Background The Affordable Care Act (ACA) has increased insurance coverage for people with HIV (PWH) in the United States. To inform health policy, it is useful to investigate how enrollment through ACA Exchanges, deductible levels, and demographic factors are associated with health care utilization and HIV clinical outcomes among individuals newly enrolled in insurance coverage following implementation of the ACA. Methods Among PWH newly enrolled in an integrated health care system (Kaiser Permanente Northern California) in 2014 (N = 880), we examined use of health care and modeled associations between enrollment mechanisms (enrolled in a Qualified Health Plan through the California Exchange vs. other sources), deductibles (none, $1–$999 and > = $1000), receipt of benefits from the California AIDS Drug Assistance Program (ADAP), demographic factors, and three-year patterns of health service utilization (primary care, psychiatry, substance treatment, emergency, inpatient) and HIV outcomes (CD4 counts; viral suppression at HIV RNA Results Health care use was greatest immediately after enrollment and decreased over 3 years. Those with high deductibles were less likely to use primary care (OR = 0.64, 95% CI = 0.49–0.84, p p = 0.03) than those with no deductible. Enrollment via the Exchange was associated with fewer psychiatry visits (rate ratio [RR] = 0.40, 95% CI = 0.18–0.86; p = 0.02), but ADAP was associated with more psychiatry visits (RR = 2.22, 95% CI = 1.24–4.71; p = 0.01). Those with high deductibles were less likely to have viral suppression (OR = 0.65, 95% CI = 0.42–1.00; p = 0.05), but ADAP enrollment was associated with viral suppression (OR = 2.20, 95% CI = 1.32–3.66, p p p = 0.01) PWH were less likely to be virally suppressed. Conclusions In this sample of PWH newly enrolled in an integrated health care system in California, findings suggest that enrollment via the Exchange and higher deductibles were negatively associated with some aspects of service utilization, high deductibles were associated with worse HIV outcomes, but support from ADAP appeared to help patients achieve viral suppression. Race/ethnic disparities remain important to address even among those with access to insurance coverage.

IntroductionWe assessed the impact of a diabetic foot ulcer prevention program incorporating once-daily foot temperature monitoring on hospitalizations, emergency department and outpatient visits, and rates of diabetic foot ulcer recurrence and lower extremity amputations for patients with recently healed foot ulcers.Research design and methodsIn this retrospective analysis of real-world data, we enrolled 80 participants with a healed diabetic foot ulcer in a year-long foot ulcer recurrence prevention program. Four outpatient centers within a large integrated healthcare system in the USA contributed to enrollment. We evaluated diabetic foot-related outcomes and associated resource utilization for participants during three periods: the 2 years before the program, the year during the program, and after the program ended. We reported unadjusted resource utilization rates during the program and the periods before and after it. We then adjusted rates of outcomes in each phase using an interrupted time series approach, explicitly controlling for overall trends in resource utilization and recurrence during the three periods.ResultsOur unadjusted data showed high initial rates of resource utilization and recurrence before enrollment in the program, followed by lower rates during the program, and higher rates of resource utilization and similar rates of recurrence in the period following the end of the program. The adjusted data showed lower rates of hospitalizations (relative risk reduction (RRR)=0.52; number needed to treat (NNT)=3.4), lower extremity amputations (RRR=0.71; NNT=6.4), and outpatient visits (RRR=0.26; absolute risk reduction (ARR)=3.5) during the program. We also found lower rates of foot ulcer recurrence during the program in the adjusted data, particularly for wounds with infection or greater than superficial depth (RRR=0.91; NNT=4.4).ConclusionsWe observed lower rates of healthcare resource utilization for high-risk participants during enrollment in a diabetic foot prevention program incorporating once-daily foot temperature monitoring.Trial registration numberNCT04345016.

Background HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. Objective The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). Methods Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. Results There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, P Conclusions These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.

Author(s): Bourgi, Kassem; Jenkins, Cathy A; Rebeiro, Peter F; Palella, Frank; Moore, Richard D; Altoff, Keri N; Gill, John; Rabkin, Charles S; Gange, Stephen J; Horberg, Michael A; Margolick, Joseph; Li, Jun; Wong, Cherise; Willig, Amanda; Lima, Viviane D; Crane, Heidi; Thorne, Jennifer; Silverberg, Michael; Kirk, Gregory; Mathews, William C; Sterling, Timothy R; Lake, Jordan; Koethe, John R; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) | Abstract: IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naive PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naive PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with g10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of g10% body weight increase at two years (adjusted odds ration=n1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

A diet high in sugar sweetened beverages (SSB), which includes soda and beverages with added sugar, has been shown to be associated with adverse health outcomes. National data indicate that one-half of adults and two-thirds of youth consume at least one SSB per day. Studies have suggested that proximity to SSB vendors and neighborhood food environment are not associated with consumption; however higher intake has been shown in adults with lower individual level education and income. Less is known about how neighborhood socioeconomic status may be associated with SSB intake. We examined SSB consumption by individual demographic and neighborhood characteristics in a large racial/ethnically and regionally diverse cohort of overweight and obese insured adults in the U.S. Data were from adults in the Patient Outcomes Research to Advance Learning (PORTAL) network-Overweight and Obese Cohort randomly selected to complete a survey in 2015 including questions of health-promoting behavior. A total of 2,683 out of 2,811 participants answered the question, “Over the past 7 days, on average, how many servings of regular soda and other sugar-sweetened drinks did you drink each day? A serving = 8 oz or ¾ can” and were included in the analysis. Responses ranged from 0 to 56 servings with median (IQR) of 0 (0,1). The study outcome was divided into 4 categories: 0, 1, 2, and 3 or more servings per day. Of the 2,683 respondents, most were non-Hispanic white (50.2%, n=1,348) with 20% non-Hispanic black (n=537), 14.8% Hispanic (n=396), and 5.5% Asian (n=148). The median (IQR) age was 54 (42, 64). The majority reported attending some college or holding a 2-year degree (35.5%, n=942) and lived in a neighborhood where > 48% of residents had a high school or lower education (28.3%, n=677) and

The shift from volume-based to value-based reimbursement has created a need for quantifying clinical performance of infectious diseases (ID) physicians. Nationally recognized ID specialty-specific quality measures will allow stakeholders, such as patients and payers, to determine the value of care provided by ID physicians and will promote clinical quality improvement. Few ID-specific measures have been developed; herein, we provide an overview of the importance of quality measurement for ID, discuss issues in quality measurement specific to ID, and describe standards by which candidate quality measures can be evaluated. If ID specialists recognize the need for quality measurement, then ID specialists can direct ID-related quality improvement, quantify the impact of ID physicians on patient outcomes, compare their performance to that of peers, and convey to stakeholders the value of the specialty.

Raltegravir became the first integrase inhibitor to gain FDA approval; but with limited evidence documenting long-term risks in real world care, especially for major health outcomes of interest.Assess raltegravir safety in clinical practice within an integrated health system.We conducted a cohort study of HIV-infected adults within Kaiser Permanente California from 2005 to 2013. We compared patients initiating raltegravir during the study period with two groups; a historical cohort (started new antiretroviral regimen [ART] 2005-2007) and a concurrent cohort that did not initiate raltegravir (2007-2013). We used multivariate Cox proportional hazard regression to obtain hazard ratios (HR) for pre-specified incident health outcomes, employing propensity scores to adjust for potential confounding.The population included 8,219 HIV-infected adults (raltegravir cohort N = 1,757; 4,798 patient-years), with greater years known HIV-infected among raltegravir patients. The raltegravir cohort had increased HR for AIDS-defining (HR 2.69 [1.53-4.71]; HR 1.85 [1.21-2.82]) and non-AIDS-defining malignancies (HR 2.26 [1.29-3.94]; HR 1.88 [1.26-2.78]) relative to both comparison cohorts. Compared to the historical cohort we found no significant difference in all-cause mortality; the raltegravir cohort experienced increased HR for all-cause mortality compared to concurrent (HR 1.53 [1.02-2.31]). Raltegravir appeared protective of lipodystrophy when compared to the historical cohort but associated with increased incidence compared to concurrent. There were no significant differences in the incidence of hepatic, skin, or cardiovascular events.The potentially elevated risk for malignancy and mortality with raltegravir and residual confounding merits further investigation. We demonstrate the value of observational cohorts for monitoring post-licensure medication safety.

Background The United States National HIV/AIDS Strategy established goals to reduce disparities in retention in human immunodeficiency virus (HIV) care, antiretroviral therapy (ART) use, and viral suppression. The impact of sex, age, and sexual HIV acquisition risk (ie, heterosexual vs same-sex contact) on the magnitude of HIV-related racial/ethnic disparities is not well understood. Methods We estimated age-stratified racial/ethnic differences in the 5-year restricted mean percentage of person-time spent in care, on ART, and virally suppressed among 19 521 women (21.4%), men who have sex with men (MSM; 59.0%), and men who have sex with women (MSW; 19.6%) entering HIV care in the North American AIDS Cohort Collaboration on Research and Design between 2004 and 2014. Results Among women aged 18-29 years, whites spent 12.0% (95% confidence interval [CI], 1.1%-20.2%), 9.2% (95% CI, .4%-20.4%), and 13.5% (95% CI, 2.7%-22.5%) less person-time in care, on ART, and virally suppressed, respectively, than Hispanics. Black MSM aged ≥50 years spent 6.3% (95% CI, 1.3%-11.7%), 11.0% (95% CI, 4.6%-18.1%), and 9.7% (95% CI, 3.6%-16.8%) less person-time in these stages, respectively, than white MSM ≥50 years of age. Among MSM aged 40-49 years, blacks spent 9.8% (95% CI, 2.4%-16.5%) and 11.9% (95% CI, 3.8%-19.3%) less person-time on ART and virally suppressed, respectively, than whites. Conclusions Racial/ethnic differences in HIV care persist in specific populations defined by sex, age, and sexual HIV acquisition risk. Clinical and public health interventions that jointly target these demographic factors are needed.

BACKGROUND Cutaneous melanoma incidence may be modestly elevated in people with HIV (PWH) vs. people without HIV. However, little is known about the relationship of immunosuppression, HIV replication, and antiretroviral therapy (ART) with melanoma risk. METHODS PWH of white race in the North American AIDS Cohort Collaboration on Research and Design were included. A standardized incidence ratio was calculated comparing risk with the white general population, standardizing by age, sex, and calendar period. Associations between melanoma incidence and current, lagged, and cumulative measures of CD4 count, HIV RNA level, and ART use were estimated with Cox regression, adjusting for established risk factors such as age and annual residential ultraviolet B (UVB) exposure. RESULTS Eighty melanomas were diagnosed among 33,934 white PWH (incidence = 40.75 per 100,000 person-years). Incidence was not elevated compared with the general population [standardized incidence ratio = 1.15, 95% confidence interval (95% CI) = 0.91 to 1.43]. Higher melanoma incidence was associated with older age [adjusted hazard ratio (aHR) per decade increase = 1.50, 95% CI = 1.20 to 1.89] and higher UVB exposure (aHR for exposure ≥35 vs.

OBJECTIVES: The National Patient-Centered Clinical Research Network (PCORnet) supports observational and clinical research using healthcare data. The PCORnet Antibiotics and Childhood Growth Study is one of PCORnet’s inaugural observational studies. The objectives of this manuscript are to describe (1) the processes used to integrate and analyze data from children across 36 participating institutions and (2) the cohort characteristics and prevalence of antibiotic use. METHODS: We included children in the cohort if they had at least one same-day height and weight measured in each of three age periods: 1) before 12 months, 2) 12 to 30 months, and 3) after 24 months. We distributed statistical queries that each institution ran on its local version of the PCORnet Common Data Model, with aggregate data returned for analysis. We defined overweight or obesity as age-sex-specific body mass index ≥ 85(th), obesity ≥95(th) percentile, and severe obesity ≥120% of the 95(th) percentile. RESULTS: 681,739 children met the cohort inclusion criteria and were racially/ethnically diverse (24.9% black, 17.5% Hispanic). Before 24 months, 55.2% of children received at least one antibiotic prescription; 21.3% received a single antibiotic prescription, 14.3% received four or more, and 33.3% received a broad spectrum antibiotic. Overweight and obesity prevalence was 27.6% at 4 to

Hepatitis C virus infection remains a significant global health problem. Many individuals are unaware of their infection or disease stage. Innovations in care that promote rapid and easy identification of at-risk populations for screening, comprehensive diagnostic screening, and triage to curative direct-acting antiviral medications will accelerate efforts to eradicate hepatitis C.

ObjectiveWith combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to ever smoking cigarettes.DesignObservational cohort of HIV-infected participants with 270 136 person-years of follow-up in the North American AIDS Cohort Collaboration on Research and Design consortium. Among 52 441 participants, 2306 were diagnosed with cancer during 2000-2015.Main outcome measuresEstimated hazard ratios and population-attributable fractions (PAF) associated with ever cigarette smoking for all cancers combined, smoking-related cancers, and cancers that were not attributed to smoking.ResultsPeople with cancer were more frequently ever smokers (79%) compared with people without cancer (73%). Adjusting for demographic and clinical factors, cigarette smoking was associated with increased risk of cancer overall [hazard ratios = 1.33 (95% confidence interval: 1.18-1.49)]; smoking-related cancers [hazard ratios = 2.31 (1.80-2.98)]; lung cancer [hazard ratios = 17.80 (5.60-56.63)]; but not nonsmoking-related cancers [hazard ratios = 1.12 (0.98-1.28)]. Adjusted PAFs associated with ever cigarette smoking were as follows: all cancers combined, PAF = 19% (95% confidence interval: 13-25%); smoking-related cancers, PAF = 50% (39-59%); lung cancer, PAF = 94% (82-98%); and nonsmoking-related cancers, PAF = 9% (1-16%).ConclusionAmong HIV-infected persons, approximately one-fifth of all incident cancer, including half of smoking-related cancer, and 94% of lung cancer diagnoses could potentially be prevented by eliminating cigarette smoking. Cigarette smoking could contribute to some cancers that were classified as nonsmoking-related cancers in this report. Enhanced smoking cessation efforts targeted to HIV-infected individuals are needed.

Background: Clinicopathological characteristics and prognosis for patients with HIV (PWH) and T-cell lymphomas (TCLs) in the current antiretroviral therapy (ART) era remains unknown. The primary objective of this study was to determine outcomes of patients with mature T and NK/T-cell lymphomas with and without HIV (PWoH) in North America. A secondary objective was to define variations in the survival of patients with TCLs and AIDS-defining B-cell lymphomas (A-BCLs) in the presence of ART. Methods: The study population included patients from two source populations, the NA-ACCORD (The North American AIDS Cohort Collaboration on Research and Design) and COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma), both of which have been previously described. The NA-ACCORD collaborates with >20 longitudinal cohorts of adults (aged ≥ 18 years) with HIV in the United States and Canada. Within the NA-ACCORD cohort, we included patients with a validated incidental diagnosis of mature T and NK/TCL (n=52) or the most common A-BCLs including Burkitt's lymphoma (n=101), diffuse large B-cell lymphoma (DLBCL, n=500) and primary CNS lymphoma (PCNSL, n=64) between 1996 and 2016. COMPLETE is a prospective, multicenter cohort study of patients with newly diagnosed incidental mature TCLs in the United States between 2010 and 2014. Of the 452 eligible patients, 450 were included for analysis after exclusion of two patients with HIV infection. Patients were followed from diagnosis to the first of death, loss to follow-up or administrative censoring at 5 years. Kaplan-Meier and log-rank tests were used to estimate and compare survival. Results: At the time of TCL diagnosis, PWH were significantly younger than patients without HIV (PWoH) (49 years vs. 60 years respectively; p At the end of the 5-year follow-up period, the survival probability since TCL diagnosis was markedly lower at 0.32 (95% confidence interval [CI]: 0.21-0.49) among PWH in contrast to 0.45 (95% CI: 0.41-0.51) for PWoH. Specifically, survival probability since ALCL diagnosis was distinctively lower at 0.23 (95% CI: 0.11-0.47) among PWH in contrast to 0.76 (95% CI: 0.66-0.87) for PWoH. Mortality following lymphoma diagnosis was elevated for PWH vs. PWoH even after adjusting for statistically significant baseline clinical characteristics such as age, race, and ALCL status in multivariate analysis (adjusted HR: 1.92; 95% CI: 1.27, 2.91). Among PWH with TCL, CD4 500 (n=10) was associated with a lower survival relative to those with counts >200 and/or VL Conclusions: Our report based on two large observational cohorts in North America highlights poor outcomes for TCLs among PWH compared to PWoH. In addition, within the PWH group, our study is the first to delineate inferior survival for patients with ALCLs relative to DLBCL and Burkitt's lymphoma accentuating the need for novel therapies. However, the overall prognosis for these lymphomas among PWH has improved in the last two decades, particularly among those with CD4>200, underscoring the impact of early and sustained ART. Disclosures Alonso: Merck: Research Funding. Foss: Kyowa: Honoraria; Acrotech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Mallinckrodt: Honoraria; Daiichi Sankyo: Honoraria; Kura: Honoraria. Jain: Trillium Therapeutics, Inc: Research Funding; Acro Biotech, Inc: Research Funding; Abcuro, Inc: Research Funding.

Since 2020, the US Preventive Services Taskforce has recommended expanding hepatitis C virus (HCV) screening to include ages 18−79, in addition to baby boomers (born 1945−1965) and those at-risk for hepatitis C virus. This retrospective cohort analysis compared patients (18 years and above) tested for HCV through usual care versus a coordinator-supported program (HCV pathway) during 2015−2018 within Kaiser Permanente Mid-Atlantic States (KPMAS). In total, 131,176 patients were tested through the HCV pathway and 128,311 through usual care (non-standardized testing). Of those tested, 1.6% (HCV pathway) and 0.5% (usual care) had chronic HCV. Of those with chronic HCV, more patients tested within the HCV pathway completed hepatic transient elastography (82.6% HCV pathway vs. 45.6% usual care, p &lt, 0.001) and a gastroenterology visit (72.2% HCV pathway vs. 46.5% usual care, 0.001), and had filled prescriptions for treatment (56.5% HCV pathway vs. 40.3% usual care, 0.001). The median time to complete each step was shorter for those tested through the HCV pathway (hepatic transient elastography (26 vs. 118 days), gastroenterology visit (63 vs. 131 days), and prescription fill (222 vs. 326 days)). More patients tested through a coordinator-supported, standardized testing pathway completed the necessary testing steps, in less time, compared to usual care. These findings may inform institutions seeking to create effective population-wide testing programs for HCV and other conditions.

BACKGROUND: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. METHODS: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy–exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000–2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non–AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. RESULTS: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34–46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (P(trend) < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77–.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01–1.34). Hypertension and hypercholesterolemia most commonly co-occurred. CONCLUSIONS: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

BACKGROUND Understanding the flow of patients through the continuum of HIV care is critical to determine how best to intervene so that the proportion of HIV-infected persons who are on antiretroviral treatment and virally suppressed is as large as possible. METHODS Using immunological and virological data from the Centers for Disease Control and Prevention and the North American AIDS Cohort Collaboration on Research and Design from 2009 to 2012, we estimated the distribution of time spent in and dropout probability from each stage in the continuum of HIV care. We used these estimates to develop a queueing model for the expected number of patients found in each stage of the cascade. RESULTS HIV-infected individuals spend an average of about 3.1 months after HIV diagnosis before being linked to care, or dropping out of that stage of the continuum with a probability of 8%. Those who link to care wait an additional 3.7 months on average before getting their second set of laboratory results (indicating engagement in care) or dropping out of care with probability of almost 6%. Those engaged in care spent an average of almost 1 year before achieving viral suppression on antiretroviral therapy or dropping out with average probability 13%. For patients who achieved viral suppression, the average time suppressed on antiretroviral therapy was an average of 4.5 years. CONCLUSIONS Interventions should be targeted to more rapidly identifying newly infected individuals, and increasing the fraction of those engaged in care that achieves viral suppression.