The cenobamate-clobazam interaction- evidence of synergy in addition to pharmacokinetic interaction.

OBJECTIVES: Report insights into the pharmacokinetic and pharmacodynamic interaction between cenobamate (CNB) and clobazam (CLB), derived from data in patients enrolled at our center in a global multicenter open-label safety study of CNB. MATERIALS & METHODS: Patients in this study either took CLB at baseline (n = 6) or had CLB added after CNB titration to maximal dose (n = 5) in addition to other antiseizure medications. Clobazam was always administered as a single bedtime dose. Random serum concentrations of CLB and N-desmethylclobazam (N-CLB) were obtained. RESULTS: Baseline daily CLB doses were 20-50 mg. Sedation began in the six baseline CLB patients at CNB doses of 25-100 mg. The N-CLB/ CLB ratio increased proportionally to the CNB dose. CLB was stopped in all six patients, five of whom were ≥50% responders. Seizure control deteriorated after stopping CLB, with only one remaining responder. Clobazam was restarted at 5 mg/d in five of the six patients. At the last follow-up, four of these patients were continuing CLB; two were seizure-free and 2 were ≥50% responders. Among the five patients that added 5 mg/d CLB de novo, three were responders. All patients were still on CNB at the end of the study. DISCUSSION: Data suggest starting CLB dose reduction at CNB doses of 25-100 mg/d. Due to possible synergy, the addition of low-dose CLB could be considered in patients with incomplete response to CNB.

Misdiagnosis of lamotrigine toxicity as posterior circulation transient ischemic attack or stroke.

PURPOSE: Lamotrigine (LTG) is one of the most used antiseizure medications (ASMs). Titration is indicated for incomplete seizure control, but toxicity with vertigo, ataxia, and diplopia may ensue. Lamotrigine concentration would be the optimal diagnostic test. However, patients often receive a stroke evaluation when presenting to the emergency department (ED), leading to unnecessary cost and delayed management. We investigated the frequency of stroke evaluation for symptoms associated with LTG toxicity and attempted to identify factors leading to this expensive evaluation. METHODS: We identified adult patients treated with LTG who presented to an emergency room with dizziness, ataxia, or diplopia and received a negative stroke evaluation, between 2003 and 2018. They were among 972 patients treated with LTG for epilepsy. We collected age at time of occurrence, symptoms presented, imaging studies performed, LTG dose and serum concentration, and the time the result was available. As a denominator, we also identified patients who developed clinical LTG toxicity during the same time period. RESULTS: Thirteen patients with LTG toxicity had 16 negative stroke evaluations in the emergency room. Their mean age was 62 years (range: 43-79) as compared with 47 years for all patients treated with LTG (p < 0.0005). The mean daily LTG dose was 621 mg (range: 300-900 mg). A LTG serum concentration was requested on the day of evaluation in 7 instances, though the result was never available until at least the next day. In 4 instances, the LTG level was drawn 1-3 days after presentation. Five of the patients in this group were among 71 patients with clinical LTG toxicity and LTG concentration >20. CONCLUSION: Emergency departments will frequently call a stroke alert for patients taking LTG and presenting with symptoms consistent with LTG toxicity, particularly in seniors at greater risk of stroke. This adds not only expense but also radiation and contrast exposure from computed tomography (CT) studies. We recommend that a rapid LTG assay be made available and always ordered in patients receiving LTG, avoiding the considerable expense of an unnecessary stroke evaluation.

Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy.

Purpose: To determine plasma metabolite and metabolic pathway differences between patients with type 2 diabetes with diabetic retinopathy (DR) and without retinopathy (diabetic controls), and between patients with proliferative DR (PDR) and nonproliferative DR (NPDR). Methods: Using high-resolution mass spectrometry with liquid chromatography, untargeted metabolomics was performed on plasma samples from 83 DR patients and 90 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis, and linear regression was used to adjust for age, sex, diabetes duration, and hemoglobin A1c. Pathway analysis was performed using Mummichog 2.0. Results: In the adjusted analysis, 126 metabolic features differed significantly between DR patients and diabetic controls. Pathway analysis revealed alterations in the metabolism of amino acids, leukotrienes, niacin, pyrimidine, and purine. Arginine, citrulline, glutamic γ-semialdehyde, and dehydroxycarnitine were key contributors to these pathway differences. A total of 151 features distinguished PDR patients from NPDR patients, and pathway analysis revealed alterations in the ß-oxidation of saturated fatty acids, fatty acid metabolism, and vitamin D3 metabolism. Carnitine was a major contributor to the pathway differences. Conclusions: This study demonstrates that arginine and citrulline-related pathways are dysregulated in DR, and fatty acid metabolism is altered in PDR patients compared with NPDR patients.

Pre-vaccine plasma levels of soluble inflammatory indices negatively predict responses to HAV, HBV, and tetanus vaccines in HCV and HIV infection.

BACKGROUND: Chronic hepatitis C virus (HCV) and HIV infections are associated with impaired responses to neo-antigens contained in hepatitis A virus (HAV)/hepatitis B virus (HBV) vaccines, yet responsible mechanisms are unclear. METHODS: ACTG 5232 and CFAR0910 were clinical trials where pre-vaccine levels of plasma IP10, IL-6, sCD163 and sCD14 were measured in viremic HCV- (n = 15) or HIV-infected participants (n = 24) and uninfected controls (n = 10). Accelerated dosing HAV/HBV vaccine and tetanus booster were administered and antibody response was measured at 0, 1, 3, 8, and 24 weeks. RESULTS: Pre-vaccine plasma IP10, IL-6, and sCD14 levels were elevated in both HCV and HIV-infected participants, while sCD163 was also elevated in HCV-infected participants. Pre-immunization tetanus antibody levels were lower in HIV-infected than in uninfected participants, while vaccine induced antibody responses were intact in HCV and HIV-infected participants. After HAV/HBV vaccination, HCV and HIV-infected participants had lower and less durable HAV and HBV antibody responses than uninfected controls. Among HCV-infected participants, pre-vaccine plasma IP10, IL-6, sCD14, and sCD163 levels inversely correlated with HAV, HBV and tetanus antibody responses after vaccine. Low HAV/HBV vaccine responses in HIV-infected participants prohibited assessment of immune correlates. CONCLUSIONS: During HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine.

Evaluating Disability Insurance Assistance as a Specific Intervention by Physiatrists at a Cancer Center.

Because of their expertise, physiatrists provide disability insurance assistance for cancer survivors. In this brief report, we perform a descriptive retrospective analysis of all new (354) outpatient physiatry consultations from January 1, 2009, to December 31, 2013, at a National Cancer Institute Comprehensive Cancer Center. Disability and/or work accommodations were brought up at some point with the physiatrist during the duration of their care for 131 (37%) of 354 patients. More than 90% of the discussions took place during the first visit. Of those patients who had a documented disability/employment discussion, 58 (44.3%) of 131 patients were originally referred for disability assistance specifically, and 58 (44.3%) of 131 also had disability insurance paperwork completed by the physiatrist. Outcomes of initial physiatry disability insurance assistance were 45 (77.6%) of 58 approved/renewed, 5 (8.6%) of 58 denied, and 8 (13.8%) of 58 unknown/died during the disability application process. The median form size was 33 (SD, 25.95) items. This study is the first of its kind and provides an initial look at work-related discussions and support with disability insurance paperwork as a specific intervention provided by physiatrists at a cancer center. The results are compelling and demonstrate that physiatrists frequently provide these interventions. These interventions take considerable time and effort but are generally successful.

Community-Acquired Pyelonephritis in Pregnancy Caused by KPC-Producing Klebsiella pneumoniae.

Carbapenem-resistant Enterobacteriaceae (CRE) usually infect patients with significant comorbidities and health care exposures. We present a case of a pregnant woman who developed community-acquired pyelonephritis caused by KPC-producing Klebsiella pneumoniae. Despite antibiotic treatment, she experienced spontaneous prolonged rupture of membranes, with eventual delivery of a healthy infant. This report demonstrates the challenge that CRE may pose to the effective treatment of common infections in obstetric patients, with potentially harmful consequences to maternal and neonatal health.

Conversion from immediate-release to extended-release lamotrigine improves seizure control.

BACKGROUND: Immediate release lamotrigine (LTG-IR) dosing can be limited by peak toxicity. It is thought that peak levels are responsible for some adverse effects such as dizziness, blurred vision, double vision and unsteadiness. At the same time, trough levels may be associated with reduced seizure threshold. The use of extended release lamotrigine (LTG-XR) to replace LTG-IR will be associated with less fluctuation in drug levels-lower peak levels may reduce adverse effects and higher trough levels may improve seizure control. This hypothesis was tested by analyzing seizure control and adverse effects before and after conversion from LTG-IR to LTG-XR in patients who underwent such conversion in 2009-2011. METHODS: We searched our patient database to identify patients converted from LTG-IR to LTG-XR for persistent seizures or adverse effects from August 2009 until December 31, 2011. We included only patients who took LTG-IR and LTG-XR for at least 6 months each. We excluded patients with nonepileptic seizures, progressive cause of epilepsy, or not keeping a seizure record. We collected the following parameters: age at conversion, LTG-IR dose and dosing schedule, duration on that dose, LTG-XR dose and dosing schedule, LTG serum level before and after conversion, duration of LTG-XR treatment, seizure frequency before and after conversion, and change in adverse experience profile. We also recorded baseline AEDs and any AED change during the course of the analysis. RESULTS: Fifty five patients (26 female) satisfied the inclusion/exclusion criteria. Their mean age was 45 years (range 23 to 86). Ten were on LTG-IR monotherapy, 24 took LTG-IR plus one other AED, most commonly levetiracetam, and the remaining 21 took LTG-IR plus at least 2 other AEDs. The mean LTG-IR dose was 544 mg/day (range 150-1100 mg/day). The mean LTG-IR serum level was 11.6 (available in 53 patients-range 4.6-21 mcg/ml). Twenty six patients were converted to the same dose and one patient took a mixture of LTG-XR and LTG-IR at the same total daily dose, while 21 had their dose slightly increased and 7 had their dose slightly decreased due to adverse effects. The mean serum level after conversion was 11.8 (available in 49 patients-range 2.6-21.2 mcg/ml). As a result of the conversion, 26 patients (47%) experienced >50% reduction in seizure frequency. There was a 46% median reduction in seizure frequency overall. Seven patients reported improvement in adverse effects. CONCLUSION: A conversion from LTG-IR to LTG-XR can help improve seizure control in some individuals with drug-resistant epilepsy, in addition to improving tolerability. While it is indicated in individuals experiencing peak adverse effects, it should also be considered in patients who have received incomplete seizure control from LTG-IR.

Metabolome-wide association study of neovascular age-related macular degeneration.

PURPOSE: To determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD) and similarly-aged controls. METHODS: Metabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape. RESULTS: Of the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05). A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism. CONCLUSIONS: These data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can provide further insight into the pathophysiology of AMD.

Improving access to hepatitis C care for urban, underserved patients using a primary care-based hepatitis C clinic.

OBJECTIVE: Chronic hepatitis C affects 200 million people worldwide and is a leading cause of death from liver disease. Effective treatment is available but can be difficult to access for uninsured, urban patients. National organizations have called for improving access to hepatitis C care in these groups. We present an innovative model for expanding access to hepatitis C care for urban, underserved patients (The Grady Liver Clinic, Grady Memorial Hospital, Atlanta, Georgia). The liver clinic provides hepatitis C care by general internists in the primary care setting. METHODS: We performed a retrospective chart review of all liver clinic patients (n=807) who presented in the first 5 years of the clinic's operation. Measures included patients' demographic and hepatitis C-related characteristics; prevalence of medical, psychiatric, and substance abuse comorbidities; and treatment status. RESULTS: The liver clinic population is primarily black (76%) and uninsured (59%). Patients had difficult-to-treat characteristics, including genotype 1 hepatitis C (90%), advanced liver fibrosis (28%), and high viral loads. Sixty-seven percent had comorbid medical conditions, and 40% had psychiatric disease. Fourteen percent of patients were treated for hepatitis C during the study period. CONCLUSION: The liver clinic has proven to be a successful model for improving access to hepatitis C care for urban, underserved patients. Despite having significant hepatic disease and medical and psychiatric comorbidities, patients in the liver clinic can be successfully maintained in care and initiated on hepatitis C treatment by general internists in a primary care setting.

Lemierre's syndrome due to Fusobacterium necrophorum.

We present a case of a patient with Lemierre's syndrome caused by Fusobacterium necrophorum who developed a right frontal lobe brain abscess. We summarise the epidemiology, microbiology, pathogenesis, clinical presentation, diagnosis, complications, therapy, and outcomes of Lemierre's syndrome. F necrophorum is most commonly associated with Lemierre's syndrome: a septic thrombophlebitis of the internal jugular vein. Patients usually present with an exudative tonsillitis, sore throat, dysphagia, and unilateral neck pain. Diagnosis of septic thrombophlebitis is best confirmed by obtaining a CT scan of the neck with contrast. Complications of the disease include bacteraemia with septic abscesses to the lungs, joints, liver, peritoneum, kidneys, and brain. Treatment should include a prolonged course of intravenous beta-lactam antibiotic plus metronidazole.

The short-term effects of antioxidant and zinc supplements on oxidative stress biomarker levels in plasma: a pilot investigation.

PURPOSE: To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy. DESIGN: Prospective interventional case series. METHODS: Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7 non-AMD controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg ß-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined. RESULTS: Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet (P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls. CONCLUSIONS: This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.

Highlights of the 2012 American Association for the Study of Liver Diseases meeting.

The American Association for the Study of Liver Diseases (AASLD) held its annual meeting from November 9, 2012, through November 13, 2012, in Boston, Massachusetts. Hepatitis C virus (HCV) was prominently featured in the meeting, reflecting the rapid pace at which new developments in the field of HCV treatment are being introduced. HCV was the topic of an estimated 451 of the 2051 submitted abstracts (22%), with 148 abstracts (7.2%) focused on investigational drugs; it was also the topic of 1 presidential plenary session (top oral abstracts), 1 symposium, 10 of 37 parallel sessions (oral abstracts), and 1 debriefing session at the close of the meeting. This article will summarize some of the major findings presented at the meeting.

Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration.

PURPOSE: To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes. DESIGN: Prospective case-control study. METHODS: Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine, cystine (CySS), glutathione, isoprostane, and isofuran were measured, and participants were genotyped for polymorphisms in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes. RESULTS: CySS was elevated in cases compared with controls (P = .013). After adjustment for age, sex, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (P = .028) as well as an 8-allele CFH haplotype (P = .029) after correction for age, gender, and smoking. None of the other plasma markers was related to AMD status in our cohort. CONCLUSIONS: Our investigation of the gene-environment interaction involved in AMD revealed a relationship between a plasma biomarker of oxidative stress, CySS, and CFH genotype. These data suggest a potential association between inflammatory regulators and redox status in AMD pathogenesis.

Safety and efficacy of entecavir for the treatment of chronic hepatitis B.

Entecavir is a cyclopentyl deoxyguanosine analog that was approved for the treatment of the hepatitis B virus (HBV) in 2005. In Phase III trials, it showed potent HBV suppression with drops of 6- to 7-log copies/mL in HBV DNA at 1 year. In addition, rates of genotypic resistance in nucleos(t)ide-naïve patients are low, reaching only 1.2% after 6 years. Safety and efficacy have been established in compensated cirrhosis and HIV-coinfected patients. Studies in decompensated cirrhosis also show efficacy. Because of potent viral suppression and a large genetic barrier to resistance, entecavir is now a first-line choice in most HBV treatment guidelines and has become an integral part of the HBV treatment armamentarium.

In vitro and in vivo assessment of mu opioid receptor constitutive activity.

Constitutive (basal) signaling has been described and characterized for numerous G protein coupled receptors (GPCRs). The relevance of this activity to disease, drug discovery and development, and to clinical pharmacotherapy is just beginning to emerge. Opioid receptors were the first GPCR systems for which there was definitive evidence presented for constitutive activity, with numerous studies now published on the regulation of this activity (e.g., structure/activity of the receptor as it relates to basal activity, pharmacology of ligands that act as agonists, inverse agonists and "neutral antagonists," etc.). This chapter summarizes some of the methods used to characterize constitutive activity at the mu opioid receptor (MOR) in preclinical in vitro and in vivo model systems. This includes cell-based systems that are useful for higher throughput screening of novel ligands and for studying variables that can impact basal tone in a system. In vivo assays are also described in which constitutive activity is increased in response to acute or chronic opioid agonist exposure and where withdrawal is precipitated with antagonists that may function as inverse agonists or "neutral" antagonists. The methods described have inherent advantages and disadvantages that need to be considered in any drug discovery/development program. A brief discussion of progress toward understanding the clinical implications of MOR constitutive activity in the management of opioid addiction and chronic pain is also included in this chapter.

Development of fatal acute liver failure in HIV-HBV coinfected patients.

Coinfection with hepatitis B virus (HBV) is not uncommon in human immunodeficiency virus (HIV)-infected individuals and patients with HIV-HBV coinfection are at high risk for progression of liver disease. Current guidelines regarding the treatment of HIV infection recommend that patients who are coinfected with HIV and HBV receive highly active antiretroviral therapy (HAART) with activity against hepatitis B. While HIV-HBV coinfected patients often experience liver enzyme elevations after starting antiretroviral therapy, acute liver failure (ALF) is rare and typically occurs with older antiretroviral agents with known potential for hepatotoxicity. We describe two cases of fatal ALF in the setting of HIV-HBV coinfection after initiation of HAART. These cases occurred despite treatment with antiretrovirals that have activity against HBV and highlight the challenges in distinguishing drug hepatotoxicity and HBV immune reconstitution inflammatory syndrome. HIV-HBV coinfected patients should be monitored closely when initiating HAART, even when treatment includes agents that have activity against HBV.

In vivo characterization of the opioid antagonist nalmefene in mice.

AIMS: The current study assessed the in vivo antagonist properties of nalmefene using procedures previously used to characterize the opioid antagonists naloxone, naltrexone, 6beta-naltrexol and nalbuphine. MAIN METHODS: ICR mice were used to generate antagonist dose-response curves with intraperitoneal (i.p.) nalmefene against fixed A(90) doses of morphine in models of morphine-stimulated hyperlocomotion and antinociception. Additional dose-response curves for antagonist precipitated opioid withdrawal were run in mice treated acutely (100mg/kg, s.c., -4h) or chronically (75mg pellet, s.c., -72h) with morphine. Comparisons were made between antagonist potency and degree of precipitated withdrawal. KEY FINDINGS: Nalmefene produced dose- and time-related antagonism of morphine-induced increases in locomotor activity with a calculated ID(50) (and 95% confidence interval) of 0.014 (0.007-0.027)mg/kg. Nalmefene produced rapid reversal of morphine-induced locomotor activity (5.1min for 50% reduction in morphine effect). A 0.32mg/kg dose of nalmefene produced blockade of morphine-induced antinociception in the 55 degrees C tail-flick test that lasted approximately 2h. Nalmefene was able to potently precipitate withdrawal in mice treated acutely or chronically with morphine. SIGNIFICANCE: These results demonstrate that nalmefene is similar to naloxone and naltrexone with respect to its in vivo pharmacology in mice. Specifically, nalmefene produces potent antagonism of morphine agonist effects while precipitating severe withdrawal. The compound has a slower onset and longer duration of action compared to naloxone and naltrexone. The data allows for a more complete preclinical comparison of nalmefene against other opioid antagonists including the putative opioid neutral antagonist 6beta-naltrexol.

Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration.

PURPOSE: Genetic factors influence an individual's risk for developing neovascular age-related macular degeneration (AMD), a leading cause of irreversible blindness. Previous studies on the potential genetic link between AMD and vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and vascular permeability, have yielded conflicting results. In the present case-control association study, we aimed to determine whether VEGF or its main receptor tyrosine kinase VEGFR-2 is genetically associated with neovascular AMD. METHODS: A total of 515 Caucasian patients with neovascular AMD and 253 ethically-matched controls were genotyped for polymorphisms in the VEGFA and VEGFR-2 genes. A tagging single nucleotide polymorphism (tSNP) approach was employed to cover each gene plus two kilobases on each side, spanning the promoter and 3' untranslated regions. SNPs with a minimum allele frequency of 10% were covered by seven tSNPs in VEGFA and 20 tSNPs in VEGFR-2. Two VEGFA SNPs previously linked with AMD, rs1413711 and rs3025039, were also analyzed. RESULTS: The 29 VEGFA and VEGFR-2 SNPs analyzed in our cohort demonstrated no significant association with neovascular AMD. A single rare haplotype in the VEGFR-2 gene was associated with the presence of neovascular AMD (p=0.034). CONCLUSIONS: This study is the first to investigate the association of VEGFR-2 polymorphisms with AMD and evaluates VEGFA genetic variants in the largest neovascular AMD cohort to date. Despite the angiogenic and permeability-enhancing effects of VEGF/VEGFR-2 signaling, we found minimal evidence of a significant link between polymorphisms in the VEGFA and VEGFR-2 genes and neovascular AMD.

Acute hepatitis C and HIV coinfection.

Hepatitis C is a common infection worldwide, but acute infection is often asymptomatic and difficult to diagnose. People coinfected with HIV and hepatitis C might progress to chronic liver disease more quickly. We present a case of a man infected with HIV with sexually acquired acute hepatitis C and discuss the immunology, natural history, and epidemiology of acute hepatitis C and coinfection with HIV. Several recent reports have documented acute hepatitis C among men who have sex with men who engage in high risk sexual practices and often have concomitant genital ulcer disease. We review treatment options for the medical management of acute hepatitis C and coinfection with HIV.