HIV-1 coinfection and morphine coexposure severely dysregulate hepatitis C virus-induced hepatic proinflammatory cytokine release and free radical production: increased pathogenesis coincides with uncoordinated host defenses.

Coinfection with human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV) is a global problem that is more prevalent in injection drug users because they have a higher risk for acquiring both viruses. The roles of inflammatory cytokines and oxidative stress were examined in HIV-1- and HCV-coinfected human hepatic cells. Morphine (the bioactive product of heroin), HIV-1 Tat and the MN strain gp120 (gp120(MN)) proteins, and X4 HIV-1(LAI/IIIB) and R5 HIV-1(SF162) isolates were used to study the mechanisms of disease progression in HCV (JFH1)-infected Huh7.5.1 cell populations. HCV increased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release and augmented production of reactive oxygen species (ROS), nitric oxide (NO), and 3-nitrotyrosine (3-NT) in Huh7.5.1 cells. Morphine preferentially affected R5-tropic, but not X4-tropic, HIV-1 interactions with Huh7.5.1 cells. HIV-1 proteins or isolates increased cytokine release in HCV-infected cells, while adding morphine to coinfected cells caused complex imbalances, significantly disrupting cytokine secretion depending on the cytokine, morphine concentration, exposure duration, and particular pathogen involved. Production of ROS, NO, and 3-NT increased significantly in HCV- and HIV-1-coexposed cells while exposure to morphine further increased ROS. The proteasome inhibitor MG132 significantly decreased oxyradicals, cytokine levels, and HCV protein levels. Our findings indicate that hepatic inflammation is increased by combined exposure to HCV and HIV-1, that the ubiquitin-proteasome system and NF-κB contribute to key aspects of the response, and that morphine further exacerbates the disruption of host defenses. The results suggest that opioid abuse and HIV-1 coinfection each further accelerate HCV-mediated liver disease by dysregulating immune defenses.

Pharmacist Statin Prescribing Initiative in Diabetic Patients at an Internal Medicine Resident Clinic.

BACKGROUND: Despite general increases in statin use in the United States, statin therapy may be underutilized in diabetic patients and vulnerable populations. OBJECTIVE: To determine the impact of a collaborative pharmacist initiative on statin prescribing for diabetic patients in an internal medicine residency clinic. The primary outcome was the change in prevalence of patients on statin therapy before and after intervention implementation. Secondary outcomes included recommendation acceptance rates and reported adverse effects. METHODS: This was a single-center, quasi-experimental pre-post intervention study. The study site was a hospital-based primary care residency clinic serving patients regardless of financial or insurance status. Diabetic patients 40 to 75 years old who were not on a statin and had an upcoming primary care physician appointment were included. Over 3 months, a clinical pharmacist and pharmacy resident evaluated clinical appropriateness and cost of statin therapy, provided recommendations to physicians, facilitated statin prescribing, and provided patient education. RESULTS: Of 454 patients, 343 were on statin therapy (75.6%) prior to the initiative. The mean age was 58 years, 59.7% were female, 76.4% were black, and 90% had hypertension. After implementation, 375 (82.6%) patients were on statins (P < .0001). Recommendations were well received (90.2% accepted) and no significant adverse effects were reported. CONCLUSION: Pharmacist implementation of a collaborative, patient-centered initiative increased statin prescribing in diabetic patients, most of which were black and had hypertension, in an internal medicine resident clinic.