Tenofovir disoproxil fumarate-associated hypophosphatemia as determined by fractional excretion of filtered phosphate in HIV-infected patients.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) -containing regimens have been associated with nephrotoxicity and hypophosphatemia in HIV-infected patients. The objective of this study was to assess the possible risk factors for hypophosphatemia and evaluate the relationship between fractional excretion of filtered phosphate (FePi) and hypophosphatemia in TDF users. PATIENT AND METHODS: Patients were enrolled in a prospective cohort study between January 2011 and December 2014. We classified experienced HIV-infected patients (individuals maintained on antiretroviral therapy (ART) for 6 months or more) and naïve patients into 3 treatment groups: TDF-containing ART (group 1), non-TDF-containing ART (never received TDF or had not received TDF in the past 6 months; group 2) and naive to antiretroviral therapy (group 3). Specimens from each individual were assessed for serum phosphate, serum creatinine, urine phosphate, and urine creatinine. Multivariable logistic regression was performed to control for the following variables measured at baseline: eGFR, age, sex, sexual orientation, injection drug use (IDUs), HIV-RNA viral load, and CD4 cell count. RESULTS: The frequency of hypophosphatemia in groups 1, 2, and 3 was 20.2%, 7.2%, and 14.6%, respectively (P = 0.002). FePi above 10% also was significantly associated with hypophosphatemia (P = 0.003; adjusted odds ratio = 2.54). Patients with elevated CD4 cell counts (>500 cells/µL) exhibited a lower risk of hypophosphatemia (P = 0.002; adjusted odds ratio = 0.35). CONCLUSIONS: Hypophosphatemia is a multifactorial etiology; FePi was confirmed as a suggested method to predict the risk of hypophosphatemia in TDF users. Clinical Trial Number: TYGH103011.

Grazoprevir/elbasvir in peginterferon alfa plus ribavirin experienced patients with chronic genotype 1 HCV/HIV co-infection: a non-randomized, open-label clinical trial.

Background and aims: We aimed to evaluate the efficacy and tolerability of grazoprevir/elbasvir in patients with chronic genotype 1 hepatitis C virus (HCV) and HIV co-infection who experienced peginterferon alfa plus ribavirin (PegIFN/RBV) (clinicaltrials.gov NCT03098121). Methods: This non-randomized, open-label trial study was conducted in Taoyuan General Hospital. HIV-infected patients were screened for HCV antibody since June 1, 2012, and HCV and HIV co-infected patients were tested for HCV RNA. The subjects who experienced PegIFN/RBV were enrolled in the study, and of whom with chronic genotype 1a or 1b received grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination tablet once daily with or without ribavirin for 12 to 16 weeks. Results: Of 2,419 HIV-infected patients, 40 patients with chronic genotype 1 HCV and HIV co-infection who failed PegIFN/RBV treatment were enrolled. Sixteen patients had genotype 1a and 24 patients had genotype 1b, with or without cirrhosis. The median age was 42 (41-47) years, and 5 patients (12.5%) were diagnosed with liver cirrhosis (child Pugh score A). The median CD4 count was 504 cells/µL (321-689). All patients (100%) had HIV viral load <200 copies/mL, and HCV viral load was 6.3 log10 IU/mL (3.98-7.12). At the end of treatment, all patients (100%, 40/40) had undetectable HCV viral load, and 95.0% (38/40) of patients achieved sustained virologic response at 12 weeks. Conclusion: Grazoprevir/elbasvir was effective in genotype 1 patients co-infected with HIV with or without cirrhosis. This finding is consistent with that of previous trials of this regimen in monoinfected population.

Lipid-lowering agents for dyslipidemia in patients who were infected with HIV in Taoyuan, Taiwan.

INTRODUCTION: There is no doubt that highly active antiretroviral therapy (ART) has decreased the total mortality of HIV-infected populations drastically, and HIV has become a chronic and manageable condition. However, complications after long-term treatment of ART tarnished the great efforts. We aimed to study the effects of add-on lipid-lowering agents on ART for patients who developed hyperlipidemia after HIV treatment. The risk factors for failure to normalize lipid profile were analyzed. MATERIALS AND METHODS: HIV-infected patients who visited outpatient clinics of Taoyuan General Hospital between July 2013 and January 2014 were retrospectively reviewed. Subjects who needed the management of dyslipidemia were enrolled. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were regularly followed up for at least 6 months. ART modification and add-on lipid-lowering agents for dyslipidemia were analyzed. RESULTS: There were 926 HIV-infected patients undertaking ART in the hospital during the study period. Among them, 23.2% of patients undergoing lopinavir-based regimen, 8.4% efavirenz-based regimen, 4.2% darunavir-based regimen, 3.3% nevirapine-based regimen, 2.4% raltegravir-based regimen and 2.3% atazanavir-based regimen developed dyslipidemia. There were 76 patients (8.2%) who needed management of dyslipidemia (Table 1). Among them, 97% received lipid-lowering agents, and 17% switched to lipid-friendly ART (atazanavir, boosted atazanavir, boosted darunavir, nevirapine or raltegravir) despite statins or fibrates used. Mean values (mg/dL) of TC/ TG/LDL were, respectively, 279/422/139 before enrolment, 209/270/114 at 4-12 weeks and 206/250/121 at 48 weeks (p<0.05 for baseline compared to 4-12 weeks and 1 year, respectively). No obvious changes in HDL were noted. In Cox proportional hazard model, patients who received lopinavir (adjusted hazard ratio [aHR], 0.293; 95% confidence interval [CI], 0.110-0.784; p=0.015) or efavirenz (aHR, 0.185; 95% CI, 0.072-0.447; p=0.005) were less likely to achieve normalization of TC (<200 mg/dL) and TG (<200 mg/dL). Modification of ART (aHR, 1.807; 95% CI, 0.828-3.944; p=0.137) did not change the outcome (Figure 1). CONCLUSIONS: Efavirenz and lopinavir were independent factors for the persistence of dyslipidemia despite adding lipid-lowering agents. ART associated with a favourable lipid profile would be considered in the modern era, and this certainly leaves the question of cost versus benefit.