Computerized Adjudication of Coronary Heart Disease Events Using the Electronic Medical Record in HIV Clinical Research: Possibilities and Challenges Ahead

This pilot study assessed feasibility of computer-assisted electronic medical record (EMR) abstraction to ascertain coronary heart disease (CHD) event hospitalizations. We included a sample of 87 hospitalization records from participants the University of North Carolina (UNC) site of the Women's Interagency HIV Study (WIHS) and UNC Center for AIDS Research (CFAR) HIV Clinical Cohort who were hospitalized within UNC Healthcare System from July 2004 to July 2015. We compared a computer algorithm utilizing diagnosis/procedure codes, medications, and cardiac enzyme levels to adjudicate CHD events [myocardial infarction (MI)/coronary revascularization] from the EMR to standardized manual chart adjudication. Of 87 hospitalizations, 42 were classified as definite, 25 probable, and 20 non-CHD events by manual chart adjudication. A computer algorithm requiring presence of ≥1 CHD-related International Classification of Diseases, 9th Revision (ICD-9)/Current Procedural Terminology (CPT) code correctly identified 24 of 42 definite (57%), 29 of 67 probable/definite CHD (43%), and 95% of non-CHD events; additionally requiring clinically defined cardiac enzyme levels or administration of MI-related medications correctly identified 55%, 42%, and 95% of such events, respectively. Requiring any one of the ICD-9/CPT or cardiac enzyme criteria correctly identified 98% of definite, 97% of probable/definite CHD, and 85% of non-CHD events. Challenges included difficulty matching hospitalization dates, incomplete diagnosis code data, and multiple field names/locations of laboratory/medication data. Computer algorithms comprising only ICD-9/CPT codes failed to identify a sizable proportion of CHD events. Using a less restrictive algorithm yielded fewer missed events but increased the false-positive rate. Despite potential benefits of EMR-based research, there remain several challenges to fully computerized adjudication of CHD events

Opioid misuse among persons with HIV engaged in care in the Southeastern US

The prevalence of opioid misuse by people living with HIV (PLWH) during the current US opioid epidemic has not been fully described. Among a cohort of persons engaged in HIV care in North Carolina, we examined the prevalence of and risk factors for opioid misuse, defined as self-reported “street” opioid use (e.g., heroin) or nonmedical prescription opioid use on a patient reported outcomes survey. Recent (past three-month) opioid misuse among 1,440 PLWH in care 2012–2017 was 2% (95% CI 2-3%) and lifetime misuse 15% (13-16%). Persons reporting lifetime or recent misuse more commonly had hepatitis C and reported injecting drugs. In multivariable logistic regression models, male-to-male sexual contact was inversely associated with recent or lifetime misuse. White/non-Hispanic race/ethnicity was associated with lifetime misuse and CD4 count and viral load were not associated with opioid misuse. Among 32 persons reporting recent misuse, 81% had a contemporaneous viral load <50 copies/mL. In this cohort of PLWH engaged in care, recent opioid misuse prevalence was similar to general population estimates. Assessments of opioid misuse among PLWH not in care are urgently needed to fully characterize the impact of opioids on all PLWH

Longitudinal opioid use among HIV-infected patients, 2000 to 2014

Longitudinal opioid prescription use is unknown among HIV-infected patients. Group-based trajectory modeling followed by multinomial logistic regression was used to identify distinct trajectories and their association with baseline characteristics among 1239 HIV-infected UNC CFAR HIV Clinical Cohort participants, 2000-2014. Three trajectories were identified: (1) 72% never/sporadic opioid use (referent group), (2) 11% episodic use (associated with female sex, depression, drug-related diagnoses, antiretroviral therapy use, and undetectable HIV RNA), and (3) 16% chronic use (associated with older age, female sex, and mental health diagnoses). Overall, opioid prescription decreased substantially with longer time in HIV care among both episodic and chronic users

Voter Registration among People with HIV in North Carolina

Persons with HIV (PWH) represent a socially and medically vulnerable population who often depend on public resources. We examined voter registration among PWH in North Carolina. Sixty-four percent were registered to vote. Registration was lower among PWH who were young, Hispanic, publicly insured or uninsured, and who had poor HIV health status

Reply

To the Editors: In their letter, Drobeniuc and Spaulding question the selected analytic approach to our randomized controlled trial of a comprehensive intervention to maintain plasma HIV RNA suppression after prison release. Specifically, issue is taken with the use of an intent-to-treat analysis comparing the rates of virologic suppression at 24 weeks after prison release between the 2 study arms

Evaluating the incident user design in the HIV population: incident use versus naive?

INTRODUCTION: The incident user design is the preferred study design in comparative effectiveness (CER) research. Usually, 180-365 days of exposure free time is adequate to remove biases associated with inclusion of prevalent users. In HIV research, the use of antiretrovirals (ARVs) at any time in the past may influence future treatment choices and CER results; thus, identifying naive as opposed to incident users is of importance. We examined misclassification of antiretroviral naive status based on Medicaid administrative data through linkage to the UNC CFAR HIV Clinical Cohort (UCHCC). METHODS: We identified Medicaid patients with incident exposure to common first-line ARV regimens between 2002 and 2008 that were also patients enrolled in the UCHCC. We calculated the proportion of antiretroviral naive patients based on the UCHCC, among patients identified as having incident exposure in Medicaid and examined factors associated with being antiretroviral naive in both data sources using logistic regression to generate prevalence odds ratios and associated 95% confidence intervals. RESULTS: Of the 3500 Medicaid patients with incident antiretroviral (ARV) exposure, 1344 were also enrolled in the UCHCC. In this sample, 34% were antiretroviral naive at the time of first exposure in the Medicaid data based on the UCHCC. In multivariable models, higher CD4 cell counts and log HIV RNA values were associated with being antiretroviral naive in both data sources. CONCLUSIONS: Administrative data are an important source of information related to HIV treatment. As the construction of a durable and long-lasting HIV treatment plan involves knowledge of current and past antiretroviral therapy, augmentation of this data with comprehensive clinical cohort information is necessary

Increased Persistence of Initial Treatment for HIV Infection with Modern Antiretroviral Therapy

Background: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used. Setting: An observational clinical cohort study in the Southeastern United States. Methods: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non-nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI. Conclusions: Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure

HIV Care Initiation Delay among Rural Residents in the Southeastern United States, 1996 to 2012

Background: Delaying HIV care initiation may lead to greater morbidity, mortality, and further HIV transmission. Rural residence may be associated with delayed diagnosis and linkage to care, with negative clinical outcomes. Objective: To examine the association between rural patient residence and CD4 cell count at HIV care initiation in a large HIV clinical cohort in the Southeastern United States. Methods: We included HIV-infected patients who initiated care between 1996 and 2012 with a geocodable address and no previous history of HIV clinical care. Patient residence was categorized as urban or rural using United States Department of Agriculture Rural Urban Commuting Area codes. Multivariable linear regression models were fit to estimate the association between patient residence and CD4 cell count at HIV care initiation. Results: Among 1396 patients who met study inclusion criteria, 988 had a geocodable address. Overall, 35% of patients resided in rural areas and presented to HIV care with a mean CD4 cell count of 351 cells/mm 3 (SD, 290). Care initiation mean CD4 cell counts increased from 329 cells/mm 3 (SD, 283) in 1996-2003 to 391 cells/mm 3 (SD, 292) in 2008-2012 (P = 0.006). Rural in comparison with urban patients presented with lower CD4 cell counts with an unadjusted and adjusted mean difference of -48 cells/mm 3 [95% confidence interval, -86 to -10) and -37 cells/mm 3 (95% confidence interval: -73 to -2), respectively, consistently observed across calendar years. Conclusions: HIV care initiation at low CD4 cell counts was common in this Southeastern US cohort and more common among rural area residents

Non-initiation of hepatitis C virus antiviral therapy in patients with human immunodeficiency virus/hepatitis C virus co-infection

AIM: To assess whether reasons for hepatitis C virus (HCV) therapy non-initiation differentially affect racial and ethnic minorities with human immunodeficiency virus (HIV)/HCV co-infection. METHODS: Analysis included co-infected HCV treatment- naïve patients in the University of North Carolina CFAR HIV Clinical Cohort (January 1, 2004 and December 31, 2011). Medical records were abstracted to document non-modifiable medical (e.g. , hepatic decompensation, advanced immunosuppression), potentially modifiable medical (e.g. , substance abuse, severe depression, psychiatric illness), and non-medical (e.g. , personal, social, and economic factors) reasons for non-initiation. Statistical differences in the prevalence of reasons for non-treatment between racial/ethnic groups were assessed using the two-tailed Fisher's exact test. Three separate regression models were fit for each reason category. Odds ratios and their 95%CIs (Wald's) were computed. RESULTS: One hundred and seventy-one patients with HIV/HCV co-infection within the cohort met study inclusion. The study sample was racially and ethnically diverse; most patients were African-American (74%), followed by Caucasian (19%), and Hispanic/other (7%). The median age was 46 years (interquartile range = 39-50) and most patients were male (74%). Among the 171 patients, reasons for non-treatment were common among all patients, regardless of race/ethnicity (50% with ≥ 1 non-modifiable medical reason, 66% with ≥ 1 potentially modifiable medical reason, and 66% with ≥ 1 non-medical reason). There were no significant differences by race/ethnicity. Compared to Caucasians, African-Americans did not have increased odds of nonmodifiable [adjusted odds ratio (aOR) = 1.47, 95%CI: 0.57-3.80], potentially modifiable (aOR = 0.72, 95%CI: 0.25-2.09) or non-medical (aOR = 0.90, 95%CI: 0.32-2.52) reasons for non-initiation. CONCLUSION: Race/ethnicity alone is not predictive of reasons for HCV therapy non-initiation. Targeted interventions are needed to improve access to therapy for all co-infected patients, including minorities

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations

OBJECTIVE: To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance. DESIGN: Prospective clinical cohort of HIV-infected patients at the University of North Carolina. METHODS: Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016. RESULTS: A total of 3682 patients contributed 23 169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes. CONCLUSION: Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently