E. Jennifer Edelman

The Next Therapeutic Challenge in HIV: Polypharmacy

With the adoption of combination antiretroviral therapy (ART), most HIV-infected individuals in care are on five or more medications and at risk of harm from polypharmacy, a risk that likely increases with number of medications, age, and physiologic frailty. Established harms of polypharmacy include decreased medication adherence and increased serious adverse drug events, including organ system injury, hospitalization, geriatric syndromes (falls, fractures, and cognitive decline) and mortality. The literature on polypharmacy among those with HIV infection is limited, and the literature on polypharmacy among non-HIV patients requires adaptation to the special issues facing those on chronic ART. First, those aging with HIV infection often initiate ART in their 3rd or 4th decade of life and are expected to remain on ART for the rest of their lives. Second, those with HIV may be at higher risk for age-associated comorbid disease, further increasing their risk of polypharmacy. Third, those with HIV may have an enhanced susceptibility to harm from polypharmacy due to decreased organ system reserve, chronic inflammation, and ongoing immune dysfunction. Finally, because ART is life-extending, nonadherence to ART is particularly concerning. After reviewing the relevant literature, we propose an adapted framework with which to address polypharmacy among those on lifelong ART and suggest areas for future work.

Electronic Media–Based Health Interventions Promoting Behavior Change in Youth: A Systematic Review

IMPORTANCE Little research has been done on the efficacy of electronic media-based interventions, especially on their effect on health or safety behavior. The current review systematically identified and evaluated electronic media-based interventions that focused on promoting health and safety behavior change in youth. OBJECTIVE To assess the type and quality of the studies evaluating the effects of electronic media-based interventions on health and safety behavior change. EVIDENCE REVIEW Studies were identified from searches in MEDLINE (1950 through September 2010) and PsycINFO (1967 through September 2010). The review included published studies of interventions that used electronic media and focused on changes in behavior related to health or safety in children aged 18 years or younger. FINDINGS Nineteen studies met the criteria and focused on at least 1 behavior change outcome. The focus was interventions related to physical activity and/or nutrition in 7 studies, on asthma in 6, safety behaviors in 3, sexual risk behaviors in 2, and diabetes mellitus in 1. Seventeen studies reported at least 1 statistically significant effect on behavior change outcomes, including an increase in fruit, juice, or vegetable consumption; an increase in physical activity; improved asthma self-management; acquisition of street and fire safety skills; and sexual abstinence. Only 5 of the 19 studies were rated as excellent. CONCLUSIONS AND RELEVANCE Our systematic review suggests that interventions using electronic media can improve health and safety behaviors in young persons, but there is a need for higher-quality, rigorous interventions that promote behavior change.

Risk of mortality and physiologic injury evident with lower alcohol exposure among HIV infected compared with uninfected men.

BACKGROUND HIV infected (HIV+) individuals may be more susceptible to alcohol-related harm than uninfected individuals. METHODS We analyzed data on HIV+ and uninfected individuals in the Veterans Aging Cohort Study (VACS) with an Alcohol Use Disorders Identification Test-Consumption AUDIT-C score from 2008 to 2012. We used Cox proportional hazards models to examine the association between alcohol exposure and mortality through July, 2014; and linear regression models to assess the association between alcohol exposure and physiologic injury based on VACS Index Scores. Models were adjusted for age, race/ethnicity, smoking, and hepatitis C infection. RESULTS The sample included 18,145 HIV+ and 42,228 uninfected individuals. Among HIV+ individuals, 76% had undetectable HIV-1 RNA (<500 copies/ml). The threshold for an association of alcohol use with mortality and physiologic injury differed by HIV status. Among HIV+ individuals, AUDIT-C score ≥4 (hazard ratio [HR] 1.25, 95% CI 1.09-1.44) and ≥30 drinks per month (HR, 1.30, 95% CI 1.14-1.50) were associated with increased risk of mortality. Among uninfected individuals, AUDIT-C score ≥5 (HR, 1.19, 95% CI 1.07-1.32) and ≥70 drinks per month (HR 1.13, 95% CI 1.00-1.28) were associated with increased risk. Similarly, AUDIT-C threshold scores of 5-7 were associated with physiologic injury among HIV+ individuals (beta 0.47, 95% CI 0.22, 0.73) and a score of 8 or more was associated with injury in uninfected (beta 0.29, 95% CI 0.16, 0.42) individuals. CONCLUSIONS Despite antiretroviral therapy, HIV+ individuals experienced increased mortality and physiologic injury at lower levels of alcohol use compared with uninfected individuals. Alcohol consumption limits should be lower among HIV+ individuals.

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes.

The previously undescribed heterozygous missense mutation E758K was discovered in the human AE1/SLC4A1/band 3 gene in two unrelated patients with well-compensated hereditary spherostomatocytic anemia (HSt). Oocyte surface expression of AE1 E758K, in contrast to that of wild-type AE1, required coexpressed glycophorin A (GPA). The mutant polypeptide exhibited, in parallel, strong GPA dependence of DIDS-sensitive (36)Cl(-) influx, trans-anion-dependent (36)Cl(-) efflux, and Cl(-)/HCO(3)(-) exchange activities at near wild-type levels. AE1 E758K expression was also associated with GPA-dependent increases of DIDS-sensitive pH-independent SO(4)(2-) uptake and oxalate uptake with altered pH dependence. In marked contrast, the bumetanide- and ouabain-insensitive (86)Rb(+) influx associated with AE1 E758K expression was largely GPA-independent in Xenopus oocytes and completely GPA-independent in Ambystoma oocytes. AE1 E758K-associated currents in Xenopus oocytes also exhibited little or no GPA dependence. (86)Rb(+) influx was higher but inward cation current was lower in oocytes expressing AE1 E758K than previously reported in oocytes expressing the AE1 HSt mutants S731P and H734R. The pharmacological inhibition profile of AE1 E758K-associated (36)Cl(-) influx differed from that of AE1 E758K-associated (86)Rb(+) influx, as well as from that of wild-type AE1-mediated Cl(-) transport. Thus AE1 E758K-expressing oocytes displayed GPA-dependent surface polypeptide expression and anion transport, accompanied by substantially GPA-independent, pharmacologically distinct Rb(+) flux and by small, GPA-independent currents. The data strongly suggest that most of the increased cation transport associated with the novel HSt mutant AE1 E758K reflects activation of endogenous oocyte cation permeability pathways, rather than cation translocation through the mutant polypeptide.

Drinking trajectories among HIV-infected men who have sex with men: a cohort study of United States veterans.

BACKGROUND Although high rates of alcohol consumption and related problems have been observed among HIV-infected men who have sex with men (MSM), little is known about the long-term patterns of and factors associated with hazardous alcohol use in this population. We sought to identify alcohol use trajectories and correlates of hazardous alcohol use among HIV-infected MSM. METHODS Sexually active, HIV-infected MSM participating in the Veterans Aging Cohort Study were eligible for inclusion. Participants were recruited from VA infectious disease clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh, and Washington, DC. Data from annual self-reported assessments and group-based trajectory models were used to identify distinct alcohol use trajectories over an eight-year study period (2002-2010). We then used generalized estimate equations (GEE) to examine longitudinal correlates of hazardous alcohol use (defined as an AUDIT-C score ≥4). RESULTS Among 1065 participants, the mean age was 45.5 (SD=9.2) and 606 (58.2%) were African American. Baseline hazardous alcohol use was reported by 309 (29.3%). Group-based trajectory modeling revealed a distinct group (12.5% of the sample) with consistently hazardous alcohol use, characterized by a mean AUDIT-C score of >5 at every time point. In a GEE-based multivariable model, hazardous alcohol use was associated with earning <

Patient-Reported Symptoms on the Antiretroviral Regimen Efavirenz/Emtricitabine/Tenofovir

6000 annually, having an alcohol-related diagnosis, using cannabis, and using cocaine. CONCLUSIONS More than 1 in 10 HIV-infected MSM US veterans reported consistent, long-term hazardous alcohol use. Financial insecurity and concurrent substance use were predictors of consistently hazardous alcohol use, and may be modifiable targets for intervention.

The epidemiology of substance use disorders in US Veterans: a systematic review and analysis of assessment methods

Most patients (80-90%) newly diagnosed with HIV are started on the antiretroviral regimen efavirenz, emtricitabine, and tenofovir (EFV/FTC/TDF). Existing studies of patient tolerability, however, are limited. We compared symptom experiences of patients on EFV/FTC/TDF, and the subsequent impact on health-related quality of life, with those of patients on other combination antiretroviral therapy (cART). We conducted a cross-sectional analysis of the Veterans Aging Cohort Study from February 2008 to August 2009 to compare the symptom experiences of patients on EFV/FTC/TDF vs. other cART, unadjusted and then adjusted for treatment characteristics, and comorbid disease severity. We then assessed the association between EFV/FTC/TDF use and health-related quality of life. Among the 1,759 patients in our analytic sample, EFV/FTC/TDF use was associated with fewer symptoms than was other cART. The use of EFV/FTC/TDF was independently associated with health-related quality of life, and this association was at least partially explained by symptom burden.

The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality

BACKGROUND Substance use disorders (SUDs), which encompass alcohol and drug use disorders (AUDs, DUDs), constitute a major public health challenge among US veterans. SUDs are among the most common and costly of all health conditions among veterans. OBJECTIVES This study sought to examine the epidemiology of SUDs among US veterans, compare the prevalence of SUDs in studies using diagnostic and administrative criteria assessment methods, and summarize trends in the prevalence of SUDs reported in studies sampling US veterans over time. METHODS Comprehensive electronic database searches were conducted. A total of 3,490 studies were identified. We analyzed studies sampling US veterans and reporting prevalence, distribution, and examining AUDs and DUDs. RESULTS Of the studies identified, 72 met inclusion criteria. The studies were published between 1995 and 2013. Studies using diagnostic criteria reported higher prevalence of AUDs (32% vs. 10%) and DUDs (20% vs. 5%) than administrative criteria, respectively. Regardless of assessment method, both the lifetime and past year prevalence of AUDs in studies sampling US veterans has declined gradually over time. CONCLUSION The prevalence of SUDs reported in studies sampling US veterans are affected by assessment method. Given the significant public health problems of SUDs among US veterans, improved guidelines for clinical screening using validated diagnostic criteria to assess AUDs and DUDs in US veteran populations are needed. SCIENTIFIC SIGNIFICANCE These findings may inform VA and other healthcare systems in prevention, diagnosis, and intervention for SUDs among US veterans.

The impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected, opioid-dependent patients.

ABSTRACTPurposeFor patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes—notably mortality—is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.MethodsAmong HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality.ResultsOf 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51–0.75; P < 0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67–0.98; P = 0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12–1.66; P < 0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32–0.68; P = < 0.001). No association was found between all-cause mortality and primary care visits (HR 1.12; 95% CI 0.90–1.26; P = 0.32) or urine drug testing (HR 0.96; 95% CI 0.78–1.17; P = 0.67).ConclusionsProviders should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.

Instruments to assess patient-reported safety, efficacy, or misuse of current opioid therapy for chronic pain: A systematic review

BACKGROUND Opioid dependence is a major risk factor for HIV infection, however, the impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected opioid-dependent patients is unknown. METHODS We conducted a longitudinal analysis of 303 HIV-infected opioid-dependent patients initiating buprenorphine/naloxone treatment. Outcomes included self-reported past 90-day needle-sharing and non-condom use. We assessed trends over the 12 months using the Cochran-Armitage trend test. Using generalized estimating equations, after multiple imputation, we determined factors independently associated with needle-sharing and non-condom use, including time-updated variables. We then conducted a mediation analysis to determine whether substance use explained the relationship between time since treatment initiation and needle-sharing. RESULTS Needle-sharing decreased from baseline to the fourth quarter following initiation of buprenorphine/naloxone (9% vs. 3%, p<0.001), while non-condom use did not (23% vs. 21%, p=0.10). HIV risk behaviors did not vary based on the presence of a detectable HIV-1 RNA viral load. Patients who were homeless and used heroin, cocaine/amphetamines or marijuana were more likely to report needle-sharing. Heroin use fully mediated the relationship between time since treatment initiation and needle-sharing. Women, patients who identified as being gay/lesbian/bisexual, those married or living with a partner and who reported heroin or alcohol use were more likely to report non-condom use. Older patients were less likely to report non-condom use. CONCLUSIONS While buprenorphine/naloxone is associated with decreased needle-sharing among HIV-infected opioid-dependent patients, sexual risk behaviors persist regardless of viral load. Targeted interventions to address HIV risk behaviors among HIV-infected opioid-dependent populations receiving buprenorphine/naloxone are needed.