Ryan P. Westergaard

Barriers and facilitators of hepatitis C screening among people who inject drugs: a multi-city, mixed-methods study

BackgroundPeople who inject drugs (PWID) are at high risk of contracting and transmitting and hepatitis C virus (HCV). While accurate screening tests and effective treatment are increasingly available, prior research indicates that many PWID are unaware of their HCV status.MethodsWe examined characteristics associated with HCV screening among 553 PWID utilizing a free, multi-site syringe exchange program (SEP) in 7 cities throughout Wisconsin. All participants completed an 88-item, computerized survey assessing past experiences with HCV testing, HCV transmission risk behaviors, and drug use patterns. A subset of 362 clients responded to a series of open-ended questions eliciting their perceptions of barriers and facilitators to screening for HCV. Transcripts of these responses were analyzed qualitatively using thematic analysis.ResultsMost respondents (88%) reported receiving a HCV test in the past, and most of these (74%) were tested during the preceding 12 months. Despite the availability of free HCV screening at the SEP, fewer than 20% of respondents had ever received a test at a syringe exchange site. Clients were more likely to receive HCV screening in the past year if they had a primary care provider, higher educational attainment, lived in a large metropolitan area, and a prior history of opioid overdose. Themes identified through qualitative analysis suggested important roles of access to medical care and prevention services, and nonjudgmental providers.ConclusionsOur results suggest that drug-injecting individuals who reside in non-urban settings, who have poor access to primary care, or who have less education may encounter significant barriers to routine HCV screening. Expanded access to primary health care and prevention services, especially in non-urban areas, could address an unmet need for individuals at high risk for HCV.

Incarceration Predicts Virologic Failure for HIV-Infected Injection Drug Users Receiving Antiretroviral Therapy

BACKGROUND Incarceration may lead to interruptions in antiretroviral therapy (ART) for persons receiving treatment for human immunodeficiency virus (HIV) infection. We assessed whether incarceration and subsequent release were associated with virologic failure for injection drug users (IDUs) who were previously successfully treated with ART. METHODS ALIVE is a prospective, community-based cohort study of IDUs in Baltimore, Maryland. IDUs receiving ART during 1998-2009 who successfully achieved an HIV RNA level below the limit of detection (<400 copies/mL) were followed up for development of virologic failure at the subsequent semiannual study visit. Logistic regression with generalized estimating equations was used to assess whether incarceration was independently associated with virologic failure. RESULTS Of 437 HIV-infected IDUs who achieved undetectable HIV RNA for at least one study visit, 69% were male, 95% were African-American, and 40% reported at least one incarceration during follow-up. Virologic failure occurred at 26.3% of visits after a median of 6 months since achieving undetectable HIV RNA. In multivariate analysis accounting for demographic characteristics, drug use, and HIV disease stage, brief incarceration was strongly associated with virologic failure (adjusted odds ratio, 7.7; 95% confidence interval, 3.0-19.7), although incarceration lasting >30 days was not (odds ratio, 1.4; 95% confidence interval, .8-2.6). CONCLUSIONS Among IDUs achieving viral suppression while receiving ART, virologic failure occurred with high frequency and was strongly associated with brief incarceration. Efforts should be made to ensure continuity of care both during and after incarceration to improve treatment outcomes and prevent viral resistance in this vulnerable population.

Longitudinal changes in engagement in care and viral suppression for HIV-infected injection drug users

Objective:To examine temporal trends and predictors of linkage to HIV care, longitudinal retention in care and viral suppression among injection drug users (IDUs) infected with HIV. Design:Community-based, prospective cohort study. Methods:We prospectively studied 790 HIV-infected IDUs participating in the AIDS Linked to the Intravenous Experience (ALIVE) study from 1998 through 2011. IDUs were considered linked to care if they attended any HIV care visit during follow-up and retained in care if they reported HIV clinic attendance at every semi-annual study visit. We used logistic regression to identify predictors of poor retention in care and failure to achieve sustained viral suppression in response to ART. Results:Of 790 HIV-infected IDUs studied, 740 (93.6%) were ever linked to care. The majority of IDUs (76.7%) received ART at some point during observation and of these, most (85.4%) achieved viral suppression. However, over a median of 8.7 years of follow-up, only 241 (30.5%) IDUs were continuously retained with no 6-month lapses in HIV care and only 63 (10.2%) had sustained viral suppression at every study visit after first receiving ART. Suboptimal engagement in care was associated with poor access to medical care, active drug use, and incarceration. Conclusion:Compared with national estimates of retention in care and virologic suppression in the United States, IDUs are substantially less likely to remain fully engaged in HIV care. Strategies to optimize HIV care should acknowledge the elevated risk of poor engagement in care among IDUs.

Capturing illicit drug use where and when it happens: An ecological momentary assessment of the social, physical and activity environment of using versus craving illicit drugs

AIMS To understand the environmental and contextual influences of illicit cocaine and heroin use and craving using mobile health (mHealth) methods. DESIGN Interactive mHealth methods of ecological momentary assessment (EMA) were utilized in the Exposure Assessment in Current Time (EXACT) study to assess drug use and craving among urban drug users in real time. Participants were provided with mobile devices and asked to self-report every time they either craved (without using) or used heroin or cocaine for 30 days from November 2008 through May 2013. SETTING Baltimore, MD, USA. PARTICIPANTS A total of 109 participants from the AIDS Linked to the IntraVenous Experience (ALIVE) study. MEASUREMENTS For each drug use or craving event, participants answered questions concerning their drug use, current mood and their social, physical and activity environments. Odds ratios (OR) of drug use versus craving were obtained from logistic regression models with generalized estimating equations of all reported events. FINDINGS Participants were a median of 48.5 years old, 90% African American, 52% male and 59% HIV-infected. Participants were significantly more likely to report use rather than craving drugs if they were with someone who was using drugs [adjusted odds ratio (aOR) = 1.45, 95% confidence interval (CI) = 1.13, 1.86), in an abandoned space (aOR = 6.65, 95% CI = 1.78, 24.84) or walking/wandering (aOR = 1.68, 95% CI = 1.11, 2.54). Craving drugs was associated with being with a child (aOR = 0.26, 95% CI = 0.12, 0.59), eating (aOR = 0.54, 95% CI = 0.34, 0.85) or being at the doctors office (aOR = 0.31, 95% CI = 0.12, 0.80). CONCLUSIONS There are distinct drug using and craving environments among urban drug users, which may provide a framework for developing real-time context-sensitive interventions.

The exposure assessment in current time study: implementation, feasibility, and acceptability of real-time data collection in a community cohort of illicit drug users.

Objective. We describe the study design and evaluate the implementation, feasibility, and acceptability of an ecological momentary assessment (EMA) study of illicit drug users. Design. Four sequential field trials targeting observation of 30 individuals followed for a four week period. Participants. Participants were recruited from an ongoing community-cohort of current or former injection drug users. Of 113 individuals enrolled, 109 completed study procedures during four trials conducted from November 2008 to May 2013. Methods. Hand-held electronic diaries used in the initial trials were transitioned to a smartphone platform for the final trial with identical data collection. Random-prompts delivered five times daily assessed participant location, activity, mood, and social context. Event-contingent data collection involved participant self-reports of illicit drug use and craving. Main Outcome Measures. Feasibility measures included participant retention, days of followup, random-prompt response rates, and device loss rate. Acceptability was evaluated from an end-of-trial questionnaire. Sociodemographic, behavioral, clinical, and trial characteristics were evaluated as correlates of weekly random-prompt response rates ≥80% using logistic regression with generalized estimating equations. Results. Study participants were a median of 48.5 years old, 90% African American, 52% male, and 59% HIV-infected with limited income and educational attainment. During a median followup of 28 days, 78% of 11,181 random-prompts delivered were answered (mean of 2.8 responses daily), while 2,798 participant-initiated events were reported (30% drug use events; 70% craving events). Self-reported acceptability to study procedures was uniformly favorable. Device loss was rare (only 1 lost device every 190 person-days of observation). Higher educational attainment was consistently associated with a higher response rate to random-prompts, while an association of HIV infection with lower response rates was not observed after accounting for differences in trial recruitment procedures. Conclusion. Near real-time EMA data collection in the field is feasible and acceptable among community-dwelling illicit drug users. These data provide the basis for future studies of EMA-informed interventions to prevent drug relapse and improve HIV treatment outcomes in this population.

Cross-clade simultaneous HIV drug resistance genotyping for reverse transcriptase, protease, and integrase inhibitor mutations by Illumina MiSeq

BackgroundViral resistance to antiretroviral therapy threatens our best methods to control and prevent HIV infection. Current drug resistance genotyping methods are costly, optimized for subtype B virus, and primarily detect resistance mutations to protease and reverse transcriptase inhibitors. With the increasing use of integrase inhibitors in first-line therapies, monitoring for integrase inhibitor drug resistance mutations is a priority. We designed a universal primer pair to PCR amplify all major group M HIV-1 viruses for genotyping using Illumina MiSeq to simultaneously detect drug resistance mutations associated with protease, nucleoside reverse transcriptase, non-nucleoside reverse transcriptase, and integrase inhibitors.ResultsA universal primer pair targeting the HIV pol gene was used to successfully PCR amplify HIV isolates representing subtypes A, B, C, D, CRF01_AE and CRF02_AG. The universal primers were then tested on 62 samples from a US cohort of injection drug users failing treatment after release from prison. 94% of the samples were successfully genotyped for known drug resistance mutations in the protease, reverse transcriptase and integrase gene products. Control experiments demonstrate that mutations present at ≥ 2% frequency are reliably detected and above the threshold of error for this method. New drug resistance mutations not found in the baseline sample were identified in 54% of the patient samples after treatment failure. 86% of patients with major drug resistance mutations had 1 or more mutations associated with drug resistance to the treatment regimen at the time point of treatment failure. 59% of the emerging mutations were found at frequencies between 2% and 20% of the total sequences generated, below the estimated limit of detection of current FDA-approved genotyping techniques. Primary plasma samples with viral loads as low as 799 copies/ml were successfully genotyped using this method.ConclusionsHere we present an Illumina MiSeq-based HIV drug resistance genotyping assay. Our data suggests that this universal assay works across all major group M HIV-1 subtypes and identifies all drug resistance mutations in the pol gene known to confer resistance to protease, reverse transcriptase and integrase inhibitors. This high-throughput and sensitive assay could significantly improve access to drug resistance genotyping worldwide.

Changes in sexual and drug-related risk behavior following antiretroviral therapy initiation among HIV-infected injection drug users.

Objective:To evaluate whether HAART is associated with subsequent sexual and drug-related risk behavior compensation among injection drug users (IDUs). Design:A community-based cohort study of 362 HIV-infected IDUs initiating HAART in Baltimore, Maryland. Methods:HAART use and risk behavior was assessed at 8316 biannual study visits (median 23). Using logistic regression with generalized estimating equations (GEE), we examined the effect of HAART initiation on changes in risk behavior while adjusting for sociodemographics, alcohol use, CD4+ cell count, year of initiation and consistency of HAART use. Results:At HAART initiation, participants were a median of 44.4 years old, 71.3% men and 95.3% African–American. In multivariable analysis, HAART initiation was associated with a 75% reduction in the likelihood of unprotected sex [adjusted odds ratio (aOR) 0.25; 95% confidence interval (CI), 0.19–0.32] despite no change in overall sexual activity (aOR 0.95; 0.80–1.12). Odds of any injecting decreased by 38% (aOR 0.62; 0.51–0.75) after HAART initiation. Among the subset of persistent injectors, needle-sharing increased nearly two-fold (aOR 1.99; 1.57–2.52). Behavioral changes were sustained for more than 5 years after HAART initiation and did not differ by consistency of HAART use. Reporting specific high-risk behaviors in the year prior to initiation was a robust predictor of engaging in those behaviors subsequent to HAART. Conclusion:Overall, substantial declines in sexual risk-taking and active injecting argue against significant behavioral compensation among IDUs following HAART initiation. These data also provide evidence to support identifying persons with risky pre-HAART behavior for targeted behavioral intervention.

Prospective evaluation of the ability of clinical scoring systems and physician-determined likelihood of appendicitis to obviate the need for CT

Objective To determine whether clinical scoring systems or physician gestalt can obviate the need for computed tomography (CT) in patients with possible appendicitis. Methods Prospective, observational study of patients with abdominal pain at an academic emergency department (ED) from February 2012 to February 2014. Patients over 11 years old who had a CT ordered for possible appendicitis were eligible. All parameters needed to calculate the scores were recorded on standardised forms prior to CT. Physicians also estimated the likelihood of appendicitis. Test characteristics were calculated using clinical follow-up as the reference standard. Receiver operating characteristic curves were drawn. Results Of the 287 patients (mean age (range), 31 (12–88) years; 60% women), the prevalence of appendicitis was 33%. The Alvarado score had a positive likelihood ratio (LR(+)) (95% CI) of 2.2 (1.7 to 3) and a negative likelihood ratio (LR(−)) of 0.6 (0.4 to 0.7). The modified Alvarado score (MAS) had LR(+) 2.4 (1.6 to 3.4) and LR(−) 0.7 (0.6 to 0.8). The Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score had LR(+) 1.3 (1.1 to 1.5) and LR(−) 0.5 (0.4 to 0.8). Physician-determined likelihood of appendicitis had LR(+) 1.3 (1.2 to 1.5) and LR(−) 0.3 (0.2 to 0.6). When combined with physician likelihoods, LR(+) and LR(−) was 3.67 and 0.48 (Alvarado), 2.33 and 0.45 (RIPASA), and 3.87 and 0.47 (MAS). The area under the curve was highest for physician-determined likelihood (0.72), but was not statistically significantly different from the clinical scores (RIPASA 0.67, Alvarado 0.72, MAS 0.7). Conclusions Clinical scoring systems performed equally well as physician gestalt in predicting appendicitis. These scores do not obviate the need for imaging for possible appendicitis when a physician deems it necessary.

Systematic review and meta-analysis of the accuracy of MRI to diagnose appendicitis in the general population.

To perform a systematic review and meta‐analysis of all published studies since 2005 that evaluate the accuracy of magnetic resonance imaging (MRI) for the diagnosis of acute appendicitis in the general population presenting to emergency departments.

High uptake of naloxone-based overdose prevention training among previously incarcerated syringe-exchange program participants.

BACKGROUND Incarceration is common among people who inject drugs. Prior research has shown that incarceration is a marker of elevated risk for opioid overdose, suggesting that the criminal justice system may be an important, under-utilized venue for implementing overdose prevention strategies. To better understand the feasibility and acceptability of such strategies, we evaluated the utilization of naloxone-based overdose prevention training among people who inject drugs with and without a history of incarceration. METHODS We surveyed clients who utilize a multi-site syringe exchange program (SEP) in 2 cities in the Midwestern United States. Participants completed an 88-item, computerized survey assessing history of incarceration, consequences associated with injection, injecting practices, and uptake of harm reduction strategies. RESULTS Among 543 respondents who injected drugs in the prior 30 days, 243 (43%) reported prior incarceration. Comparing those with and without a history of incarceration, there were no significant differences with respect to age, gender, or race. Those who observed an overdose, experienced overdose, and received training to administer or have administered naloxone were more likely to report incarceration. Overall, 69% of previously incarcerated clients had been trained to administer naloxone. CONCLUSION People who inject drugs with a history of incarceration appear to have a higher risk of opioid overdose than those never incarcerated, and are more willing to utilize naloxone as an overdose prevention strategy. Naloxone training and distribution is an important component of comprehensive prevention services for persons with opioid use disorders. Expansion of services for persons leaving correctional facilities should be considered.