Syringe services programs in the Bluegrass: Evidence of population health benefits using Kentucky Medicaid data.

PURPOSE: To evaluate whether Kentucky counties that established a new syringe services program realized a significant decline in the incidence rate of a set of infectious disease diagnoses commonly transmitted via injection drug use. METHODS: Longitudinal count models of within-county rates of newly diagnosed infections among populations at risk were estimated using Medicaid claims/encounters data. Generalized estimating equation models were used to report incident rate ratios of 6 diagnoses: (1) HIV; (2) hepatitis C; (3) hepatitis B; (4) osteomyelitis; (5) endocarditis; and (6) skin/soft tissue infection. To investigate whether a delay in effect was present, separate models were fit to estimate the effects of establishing a syringe services program: at its opening date, and again at 1, 3, and 6 months postopening date. FINDINGS: Taken together, the aggregated within-county incidence rate of these 6 diagnoses was significantly lower following the implementation of a syringe services program (P < .05). Our models estimated that counties which opted to open a syringe services program realized an approximate month-over-month decline in new diagnoses of 0.5% among the population at risk. CONCLUSIONS: These results lend further support to previous conclusions made in the public health literature regarding the efficacy of syringe services programs. Specifically, declines in incidence rates were observable beginning at 1 month post syringe services program opening. These results are particularly notable due to the typical setting in which these syringe services programs operated-rural communities of fewer than 40,000 residents.

Eliminating hepatitis C in a rural Appalachian county: protocol for the Kentucky Viral Hepatitis Treatment Study (KeY Treat), a phase IV, single-arm, open-label trial of sofosbuvir/velpatasvir for the treatment of hepatitis C.

OBJECTIVES: The overall goal of the Kentucky Viral Hepatitis Treatment Study (KeY Treat) is to eliminate hepatitis C transmission from a county in Appalachian Kentucky by removing the barriers to accessing hepatitis C virus (HCV) treatment. METHODS/ANALYSIS: KeY Treat is a phase IV, open-label, single-arm clinical trial of sofosbuvir/velpatasvir (SOF/VEL) for the treatment of viraemic HCV infections. Those eligible for KeY Treat are at least 18 years of age, viraemic and are residents of the target county. Pregnant women are not eligible. Rapid HCV RNA screening is used to determine eligibility, and those with a quantifiable viral load (VL) consenting to participate initiate SOF/VEL on the same day. All pharmacologic treatment and related medical care is provided free of charge using a non-specialist provider model. Follow-up visits occur at 2, 6 and 12 weeks during treatment to assess medication adherence (measured via VL and self-report), side effects and engagement in risk behaviours. Post-treatment visits occur at 12 weeks (sustained virologic response (SVR12) visit), 6 months and 12 months post-treatment completion to assess re-infection. A control county has also been identified, and prevalence and incidence of chronic HCV infections will be compared with the target community longitudinally. The primary outcome to assess elimination is SVR12. However, several outcomes will be measured to assess the effectiveness of removing the barriers to HCV treatment, including treatment entry, completion and re-infection. Analyses will be conducted via a generalised linear model framework that can incorporate flexible covariate adjustment and multiple outcome types with a compatible link function. Mathematical modelling will be completed assessing the impact and cost-effectiveness of the intervention. ETHICS AND DISSEMINATION: KeY Treat has been approved by the Institutional Review Board at the University of Kentucky. Results from KeY Treat will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03949764.

Risk factors for loss to follow-up of persons who inject drugs enrolled at syringe services programs in Kentucky.

BACKGROUND: Syringe services programs (SSP) are an effective strategy to reduce blood-borne infections of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in persons who inject drugs (PWID). The objectives of this study were to determine the frequency and risk factors for loss to follow-up (LTFU) in PWID enrolled at SSPs in Kentucky. METHODS: A retrospective cohort study was conducted which included data of PWID enrolled at 32 SSP. Demographics, use of drugs, HIV testing, HCV testing, and medical services were analyzed. A generalized linear model (GLM), family binomial was used to determine risk factors for LTFU. RESULTS: The analysis included 5742 PWID. LTFU by year of enrollment was 287/770 (37.3%) in 2017, 796/1874 (42.5%) in 2018, and 1479/3,098 (47.7%) in 2019. LTFU was significantly associated with distance to SSP from home of more than five miles (RR 1.25; 95%CI 1.09-1.43; p = 0.002) and SSPs housed in rural counties (RR 1.22; 95%CI 1.06-1.40; p = 0.004), adjusted by age, sex, and race. The use of buprenorphine was associated with less risk of LTFU (RR 0.79, p = 0.034). CONCLUSION: The distance to an SSP from home and SSPs in rural counties were identified as risk factors for LTFU. Initiatives that bring health services closer to PWID homes and offer opioid use disorder treatment may improve repeated participation in SSPs.

Use of virostatics as a means of targeting human immunodeficiency virus infection.

Current antiretroviral therapy has had a significant impact on HIV associated morbidity and mortality. Despite these positive outcomes current antiretroviral regimens have significant deficiencies which include multiple drug-drug interactions, high pill burdens, and considerable financial expense. Perhaps the greatest shortcoming is the apparent inability of current therapy to disrupt low level viremia in certain cellular reservoirs despite maximal virologic control as determined by polymerase chain reaction detection. These drug-resilient reservoirs preclude the ability to discontinue antiretrovirals while maintaining viral control. Additionally, they may be responsible at least in part for the evolution of drug resistant variants. Various researchers have proposed that certain immune modulating agents known as virostatics (i.e., hydroxyurea (HU), mycophenolate mofetil (MMF), and cyclosporine (CSA)) may have some efficacy in managing HIV disease and/or disrupting resilient reservoirs. These agents may act by reducing the pool of activated CD4+ cells which are susceptible to infection thereby inhibiting the characteristic immune over-activation seen in most HIV infected patients. Virostatics have primarily been studied in patients with advanced HIV disease and as components of trials involving structured treatment interruptions. These trials have demonstrated conflicting results with regard to viral load and CD4+ cell counts as well as potential adverse effects including immune suppression. Before widespread use of these agents can be recommended, larger, well controlled trials will need to be conducted to determine which virostatic agents are appropriate for use in HIV infected patients and the most efficacious time course within which to initiate these agents.

Results of an antimicrobial control program at a university hospital.

PURPOSE: The results of the first five years of an ongoing antimicrobial control program are reported. METHODS: In 1998, a multidisciplinary antimicrobial subcommittee of the pharmacy and therapeutics committee of a university hospital was formed and charged with making formulary interventions in an effort to reduce rising antimicrobial resistance rates and drug expenditures. In 1999, a number of measures were implemented for controlling antimicrobial use. Selected antimicrobials with the potential for inappropriate use or whose inappropriate use had been documented were placed in the control of physicians in the infectious diseases (ID) division. Prior approval by an ID physician was required before the pharmacy could dispense these agents. Other key interventions included removal of ceftazidime and cefotaxime from the formulary, restriction of vancomycin and carbapenem use, and replacement of ciprofloxacin with levofloxacin as the sole fluoroquinolone on the formulary. Data regarding antimicrobial use and expenditures between 1998 and 2002 were compared and analyzed. RESULTS: Antimicrobial use was reduced by 80% for third-generation cephalosporins and 15% for vancomycin following the implementation of the new antimicrobial policies. Antimicrobial-resistance patterns for many important gram-negative pathogens, including Pseudomonas aeruginosa, demonstrated a reversal of previous increases. In addition, the rate of methicillin-resistant Staphylococcus aureus decreased by an average of 3% each year from 1999 to 2002. Pharmacy expenditures for all antimicrobials, including antiviral, antifungal, and antibacterial agents, decreased 24.7%, with a cumulative cost saving of 1,401,126 US dollars, without inflation assumptions. CONCLUSION: The implementation of an antimicrobial control program decreased the use of selected antimicrobial agents and resulted in substantial reduction of expenditures for antimicrobials.

Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity.

Recent advances in the development of antiretrovirals have significantly extended life-spans and positively impacted morbidity of HIV-seropositive patients. While effective, antiretrovirals are associated with complex medication regimens, large pill burdens, and significant side effects which may impact quality of life. Researchers continue to examine various chemical entities in their search for agents with anti-HIV activity. Ideal agents would be efficacious, easily dosed and administered, inexpensive, and with few adverse effects. Chloroquine and its analog hydroxychloroquine are two inexpensive agents that are widely used for the treatment of malaria and have been shown to achieve some level of anti-HIV activity. The exact mechanism of chloroquine and hydroxychloroquine's anti-HIV activity has not yet been discerned but may be related to effects on HIV's surface envelope glycoprotein 120. If found efficacious, both drugs would offer significant advantages to current therapy including a unique mechanism of action, lack of cross-resistance with other antiretrovirals, and low cost. Early and limited in vitro and in vivo data have demonstrated modest anti-HIV efficacy as indicated by measures of viral burden. Effects on CD4+ cell counts have not been as pronounced. It is premature to advocate the use of either of these agents in the management of routine HIV disease; however; the drugs should be further studied to determine their benefit in the treatment of patients who have exhausted all standard treatments. Larger, well-controlled trials are needed to discern the potential role of chloroquine and hydroxychloroquine in the management of HIV.

Rash associated with piperacillin/tazobactam administration in infectious mononucleosis.

OBJECTIVE: To report a case of piperacillin/tazobactam-induced rash in a patient with infectious mononucleosis. CASE SUMMARY: A 25-year-old white man developed a rash while receiving piperacillin/tazobactam 3.375 g intravenously every 6 hours and gentamicin for osteomyelitis complicating a left femur fracture secondary to a motorcycle accident. Due to progression of the rash following additional doses of piperacillin/tazobactam during hospitalization, the patient's antimicrobial regimen was changed to vancomycin and meropenem. Subsequently, a mononucleosis spot test was positive, and both Epstein-Barr virus (EBV) immunoglobulin (Ig) G and IgM antibodies were positive. The rash rapidly resolved with the discontinuation of piperacillin/tazobactam. DISCUSSION: Although the development of rash following the administration of several different antimicrobials, especially ampicillin, has been previously reported, this is the first report of piperacillin/tazobactam-induced rash in infectious mononucleosis. The rash is generally self-limiting and usually resolves within days of discontinuing the causative antimicrobial agent. An altered drug metabolism or an immune-mediated process has been suggested as the potential mechanism for rash development. CONCLUSIONS: Prior reports of antimicrobial-induced rash in infectious mononucleosis and a positive laboratory diagnosis of EBV in our patient with no history of penicillin allergy support the identification of piperacillin/tazobactam as the inducer of the rash. According to the Naranjo probability scale, the association of piperacillin/tazobactam with the rash was classified as probable.