Nelfinavir in HIV-HCV coinfected patients: a 24-month follow-up in a cohort of 82 patients.

This retrospective and longitudinal study evaluated the long-term hepatic tolerance of a nelfinavir (NFV)-antiretroviral combined regimen in 82 patients of the HCV-HIV Cohort of CISIH-Sud of Marseilles. Follow-up data (liver enzyme levels, CD4 cell count, HIV viral load, and metabolic parameters) of patients treated with NFV on inclusion or during the follow-up of the cohort were analyzed under treatment over 24 months. Comparisons were performed with X2 or Kruskal-Wallis tests. At baseline (n = 82), the median exposure to NFV was 4.1 months; 58 patients received NFV combined with NRTI and 24 with NNRTI. The median CD4 cell count was 337/mm3 [interquartile range (IR): 216-480) and 39.7% had an undetectable HIV RNA level. Qualitative HCV PCR was positive in 91% of the patients and 19/51 patients with liver biopsy were F3-F4. Median alanine and aspartate aminotransferase (ALAT, ASAT), gamma-glutamyltransferase (GT), and alkaline phosphatase (ALP) were 46 UI/liter (IR: 36-76), 55 UI/liter (IR: 32-97), 97 UI/liter (IR: 50-194), and 88 UI/liter (IR: 72-104), respectively, with 76% of the patients with ALAT/ASAT grade <2. Median follow-up was 23 months (IR: 13.8-37). No significant difference was observed in the distribution of ALAT, ASAT, GT, and ALP as well as of ALAT/ASAT grades over the 24-month study period. Patients treated with NFV + NNRTI had significantly higher GT and ALP levels at baseline with no significant increase during follow-up. Cholesterol, triglyceride, and glycemia distributions remained stable over time. In conclusion, this study showed a good hepatic and metabolic tolerance of a long-term NFV-combined regimen in HIV-HCV coinfected patients.

Efficacy and tolerance of HCV treatment in HIV-HCV coinfected patients: the potential interaction of PI treatment.

PURPOSE: To evaluate tolerance and efficacy of an open-label interferon-ribavirin treatment and their determinants in 62 HCV-HIV coinfected patients in routine followup. METHOD: Patients received at least 6 and up to 12 months of combination interferon alpha-2b (peg or not) plus ribavirin. Determinants of therapeutic success were estimated by a multivariate logistic regression. RESULTS: Five patients stopped the study, 4 were lost to follow-up, and 53 participated in the entire therapeutic protocol. Among these 53, the end-of-treatment results showed complete clearance of HCV-RNA in 17 (32%). A sustained virologic response (SVR) after 6 or 9 months was observed in 9 (17%) patients, 3 relapsed, and data were not available for 5. Genotype 3a (odds ratio [OR] = 14.4; confidence interval [CI] = 1.84-110.3) favored SVR and treatment with protease inhibitor (PI) therapeutic resistance (OR = 14.4; CI = 1.01-200); as well, a higher fibrosis score tended to increase resistance (p =.11). Adverse events were reported by 24/53 patients (45.3%). CONCLUSION: HCV therapy associating interferon and ribavirin in HCV-HIV coinfected patients is well accepted even if tolerance is moderate. Treatment permitted SVR in at least 17% of the cases. This is likely when patients initiate treatment at the early fibrosis stage and are infected with genotype 3a. The potential interaction with PI therapy should be explored.

GI motor inhibition associated with acute exposure to methyl methacrylate vapor.

A mixture of monomeric methyl methacrylate vapor in air was delivered into the breathing air of chloralose-urethan anesthetized dogs. Fixed length exposures to 2000-ppm doses of the vapor resulted in a transient drop in arterial blood pressure and a marked inhibition of ongoing GI motor activities. Motor inhibition always continued for a variable time (approximately 10-15 min) subsequent to the cessation of methyl methacrylate vapor administration. This inhibitory response was not blocked by bilateral vagotomy, spinal transection, splanchnectomy, or the intravenous administration of tetraethylammonium chloride. Another series of experiments determined that the administration of blood from a dog receiving methyl methacrylate vapor produced GI motor inhibition in another dog not connected to the experimental gas mixture. Therefore, it is concluded that, aside from any reflex effects produced, methyl methacrylate vapor in sufficient concentration probably exerts a direct inhibitory effect upon GI smooth muscle that is mediated by the cardiopulmonary systems.