Short and long-term effects of telaprevir on kidney function in patients with hepatitis C virus infection: a retrospective cohort study.

BACKGROUND: Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment. METHODS: Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir. RESULTS: Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m2 compared to the group with baseline eGFR ≥ 90 mL/min/1.73m2 (12 vs. 18 mL/min/1.73m2, P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m2 decrease in estimated glomerular filtration rate at twelve months in an adjusted model. CONCLUSIONS: Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m2 as previously reported.

High frequency of hypothalamic-pituitary-adrenal axis dysfunction after local corticosteroid injection in HIV-infected patients on protease inhibitor therapy.

BACKGROUND: The frequency of hypothalamic-pituitary-adrenal axis dysfunction among HIV-infected patients receiving steroid injections has not been reported, and the risk factors for this adverse event are poorly characterized. METHODS: We conducted a retrospective analysis of data from HIV-infected patients in the Partners HealthCare system (Boston, MA) who received corticosteroid injection(s) between 2002 and 2011. Chart review focused on HIV status, antiretroviral therapy [eg, protease inhibitors (PI)], steroid injection(s), and adrenal axis dysfunction (eg, adrenal insufficiency and/or Cushing syndrome). Because all cases occurred among patients on PIs, we performed additional detailed data extraction and conducted univariate and multivariate analyses to identify risk factors in this group. RESULTS: One hundred seventy-one HIV-infected patients received ≥1 corticosteroid injection(s) in the study period. Nine cases (event frequency: 5.3%; 95% confidence interval: 2.4% to 9.8%) of secondary adrenal insufficiency were diagnosed; 5 (55%) of these 9 patients also had clinical evidence of Cushing syndrome. All cases occurred among the 81 patients on PIs (event frequency among those on PIs: 11.1%; 95% confidence interval: 5.2% to 20.0%). Among patients on PIs, the major risk factor for hypothalamic-pituitary-adrenal axis dysfunction was having ≥2 injections within 6 months. CONCLUSIONS: In this retrospective cohort study, 11% of HIV-infected patients on PIs at the time of steroid injection were later diagnosed with hypothalamic-pituitary-adrenal axis dysfunction. Corticosteroid injections in HIV-infected patients on PIs should only be used with great caution and close monitoring.

Successful bosentan and nonnucleoside reverse transcriptase inhibitor-based therapy in a patient with acquired immunodeficiency syndrome and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH), which can be a complication of human immunodeficiency virus (HIV) infection, is characterized by increased pulmonary arterial pressure and peripheral vascular resistance, subsequently leading to right heart failure. In HIV-infected patients, the management of PAH is challenging given the potential drug interactions between PAH-specific vasodilators and antiretroviral drugs. We describe a 51-year-old female with acquired immunodeficiency syndrome (AIDS) and HIV-associated PAH. She was treated with the oral endothelin receptor antagonist bosentan while taking a nevirapine (a nonnucleoside reverse transcriptase inhibitor)-based antiretroviral regimen. Due to concerns about potential drug interactions with the antiretroviral therapy, her nevirapine plasma concentration, as well as CD4(+) cell count and viral load, were continuously monitored. We observed no interaction between bosentan and nevirapine during a 4-year period. To our knowledge, this report is the first to demonstrate successful, long-term coadministration of bosentan and a nonnucleoside reverse transcriptase inhibitor.