Fanconi Syndrome Leading to Hypophosphatemic Osteomalacia Related to Tenofovir Use.

Tenofovir disoproxil fumarate (TDF) is used worldwide to treat and prevent Human Immunodeficiency Virus (HIV) infection. Fanconi syndrome is a complication of TDF use and is characterized by inadequate reabsorption of glucose, phosphate and protein in the proximal tubule of the kidney which may eventually lead to osteomalacia manifested by symptoms of pain, muscular weakness and difficulty ambulating. We present a patient with severe osteomalacia due to progressive and unrecognized Fanconi's syndrome, who responded rapidly to TDF withdrawal, oral phosphate repletion and calcitriol. With the widespread use of TDF-containing antiviral regimens, it is critically important that physicians adhere to screening recommendations to detect early Fanconi syndrome, and recognize symptoms of osteomalacia as a serious complication.

Treating Hepatitis C in a Ryan White-Funded HIV Clinic: Has the Treatment Uptake Improved in the Interferon-Free Directly Active Antiviral Era?

Now that highly efficacious, interferon-free (IFN-free), direct acting antivirals (DAA) for the treatment of hepatitis C (HCV) have closed the gap between treatment and cure, identifying barriers that prevent initiation of treatment is more crucial than ever. This is a retrospective study utilizing Electronic Medical Records and Prior Authorization Records to identify HCV treatment gaps, including predictors for intention-to-treat and treatment initiation in the first 15 months of a Ryan White funded human immunodeficiency virus (HIV)/HCV co-infection clinic. This study included 128 adults ≥ 18 years old with HIV and chronic HCV infection who had visited the treatment center at least once since January 2013. Provider intent-to-treat was used to differentiate patients actively considered for treatment based on documentation kept by a multidisciplinary HCV team. Members of this group who had gone on to initiate treatment were identified. Baseline characteristics were compared. Rates of active treatment consideration and treatment initiation were 30% and 14%, respectively. HCV treatment-naïve individuals were less likely to be considered for treatment [risk ratio (RR) 1.58, 95% confidence interval (CI) 1.07-2.32] and initiate therapy (RR 2.33, 95% CI 0.97-5.60). Advanced liver disease had no significant association. Black race (RR 1.96, 95% CI 0.90-4.25) and Medicaid insurance holders (RR 1.90, 95% CI 0.95-3.82) tended to be less likely to initiate therapy. The availability of IFN-free DAA regimens has yet to increase HCV treatment uptake in our HIV/HCV co-infected population. Barriers to HCV treatment initiation have shifted from medical contraindications to socioeconomic variables.

Majority of HIV/HCV Patients Need to Switch Antiretroviral Therapy to Accommodate Direct Acting Antivirals.

The impact of drug-drug interactions (DDIs) between interferon-free direct acting antiviral (DAA) regimens and antiretrovirals (ART) among HIV/HCV co-infected individuals in clinical practice settings is unknown. A single-center, retrospective chart review of co-infected patients was conducted from June 2014 to February 2015. Significant interactions between simeprevir (SMV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (3D regimen) with ART were identified based on available literature. SMV had the largest number of DDIs and was further investigated to determine the feasibility of ART switch to allow for DAA use. Of 127 subjects, 23% had advanced liver disease; 86% of those with known HCV genotype were HCV genotype 1. An ART switch allowing use of SMV, LDV, and 3D regimen was recommended in 97/127 (76%), 81/127 (64%), and 91/127 (72%) patients, respectively. Subjects on PI/r regimens had limited options for ART switch, with 40% of these patients unable to be switched to an ART regimen that avoided the use of a PI. In conclusion, the majority of HIV/HCV co-infected patients will be recommended to switch ART prior to use of interferon-free, DAA regimens, and an ART switch may not be feasible for more than a third of patients on a boosted PI. DDIs between ART and DAAs represent an additional barrier to treatment efficacy in clinical practice settings that are unaccounted for in clinical trials.