ABSTRACT
BACKGROUND & AIMS: We conducted an open-label phase 2 study to assess the efficacy and safety of the oral nucleotide polymerase inhibitor sofosbuvir in combination with ribavirin in patients of Egyptian ancestry, chronically infected with genotype 4 hepatitis C virus (HCV). METHODS: Treatment-naive and previously treated patients with genotype 4 HCV were randomly allocated in a 1:1 ratio to receive sofosbuvir 400mg and weight-based ribavirin, for 12 or 24 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response (HCV RNA <25IU/ml) 12 weeks after cessation of therapy (SVR12). RESULTS: Thirty treatment-naive and thirty previously treated patients were enrolled and treated for 12 weeks (n=31) or 24 weeks (n=29). Overall, 23% of patients had cirrhosis and 38% had diabetes. 14% of treatment-naive patients were interferon ineligible and 63% of treatment-experienced patients had prior non-response. SVR12 was achieved by 68% of patients (95% CI, 49-83%) in the 12-week group, and by 93% of patients (95% CI, 77-99%) in the 24-week group. The most common adverse events were headache, insomnia, and fatigue. No patient discontinued treatment due to an adverse event. CONCLUSIONS: The findings from the present study suggest that 24 weeks of sofosbuvir plus ribavirin is an efficacious and well tolerated treatment in patients with HCV genotype 4 infection.
Subject(s)
Hepacivirus , Hepatitis C, Chronic , Ribavirin , Sofosbuvir , Adult , Aged , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Drug Therapy, Combination/methods , Egypt , Female , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/ethnology , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , RNA, Viral/analysis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Ribavirin/administration & dosage , Ribavirin/adverse effects , Sofosbuvir/administration & dosage , Sofosbuvir/adverse effects , Treatment Outcome , United States , Viral Load/drug effects , Viral Load/methods , Viral Nonstructural Proteins/antagonists & inhibitorsABSTRACT
PURPOSE: Testosterone replacement therapy via deep intramuscular injections causes extraphysiologic variations in serum testosterone concentrations. A topical transdermal testosterone gel formulation (AndroGel(R)) provides sustained physiologic concentrations of serum testosterone. The objective of this open-label switch study was to compare pharmacokinetics, safety, tolerability, and efficacy of delivery of daily testosterone gel versus intramuscular testosterone injection every 1 or 2 weeks in hypogonadal human immunodeficiency virus (HIV)-infected men. METHOD: Patients received intramuscular testosterone (100-200 mg/wk) for 8 weeks, then switched to daily topical testosterone gel (5-10 g gel/day) for 8 weeks. Study endpoints included free serum testosterone concentrations and quality-of-life scores. RESULTS: Thirty patients (average age, 45 years) were recruited; 24 completed the study. Mean peak free testosterone concentrations with intramuscular testosterone and testosterone gel were 42 pg/mL and 23 pg/mL, respectively, and mean peaktrough fluctuations in free testosterone were 26.7 +/- 12.8 pg/mL and 2.7 +/- 10.7 pg/mL, respectively (p < .001). Quality-of-life scores indicated more improved physical and emotional well-being with gel versus intramuscular testosterone. No significant changes in laboratory parameters or lean body mass were noted. CONCLUSION: Daily testosterone gel produced stable testosterone concentrations and improved quality of life compared with intermittent intramuscular testosterone injections.
Subject(s)
Administration, Topical , HIV Infections/complications , Injections, Intramuscular , Testosterone/administration & dosage , Testosterone/deficiency , Adult , Gels , Humans , Male , Middle Aged , Prospective Studies , Quality of Life/psychology , Serum/chemistry , Testosterone/adverse effects , Testosterone/pharmacokineticsABSTRACT
PURPOSE: The purpose of this study was to evaluate the short-term effects (up to 6 months) of tenofovir disoproxil fumarate (DF) use on renal function in patients being treated for HIV-1 infection. METHOD: The charts of 447 HIV-1-infected patients who received at least three months of tenofovir DF treatment were reviewed. Data collected included demographics, concurrent antiretrovirals, other concurrent medications, CD4 counts and HIV-1 viral loads, and serum creatinine values while on tenofovir DF. Data collection was truncated at 6 months. RESULTS: Baseline serum creatinine (SCr) was 1.0 mg/dL, with a calculated creatinine clearance (CLCr) of 95.2 mL/min (using the Cockroft-Gault equation). There was no significant change in SCr or CLCr at 12 weeks (1.1 mg/dL and 92.7 mL/min, respectively) or 24 weeks (1.1 mg/dL and 92.9 mL/min, respectively). All three patients with grade 2 increases in SCr had other medical reasons for an increased SCr (one patient each had indinavir-associated nephrolithiasis, lactic acidosis, and pancreatitis). No patients experienced any complications from these increases in SCr. CONCLUSION: Increases in SCr and CLCr within the first 6 months of tenofovir DF therapy were rare. Although no clinical nephrotoxicity was observed, continued observation of renal function is warranted in patients predisposed to renal impairment.