M. Bonarek

Risk Factors for Lactic Acidosis in HIV-Infected Patients Treated with Nucleoside Reverse-Transcriptase Inhibitors: A Case-Control Study

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.

A Cohort Study of Nevirapine Tolerance in Clinical Practice: French Aquitaine Cohort, 1997–1999

We performed a retrospective study to evaluate, under routine circumstances, the tolerance and immunovirological changes associated with antiretroviral regimens that contain nevirapine in 137 patients (88% were antiretroviral experienced). During a mean follow-up of 11 months, 33% of patients reported side effects attributed to nevirapine, and 21% discontinued treatment because of poor tolerance. Administration of antihistamines or corticosteroids at the initiation of treatment was not protective against adverse events (relative risk, 0.82; 95% confidence interval, 0.49-1.38). The proportion of patients with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection who had alanine aminotransferase levels of >100 IU/L increased from 19.4% at baseline to 42.9% at month 12 of follow-up (P=.02). We noticed a significant increase of the proportion of patients with total cholesterol levels of >5.5 mM (P=.02). We have shown that there is a high level of discontinuation of nevirapine therapy in clinical practice and that side effects were not prevented by administration of antihistamines or corticosteroids. Coinfection with HCV or HBV increased the risk of hepatotoxicity, which lead to the cautious use of nevirapine for such patients.

CASE REPORT: Sarcoidosis-Associated Hepatitis C Virus Infection

: Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.