Background. Tenofovir is one of the most widely used antiretroviral drugs. Tenofovir undergoes renal clearance by a combination of glomerular filtrat

Ribavirin in combination with pegylated interferon α is the current standard treatment for chronic hepatitis C. Adequate exposure to ribavirin seems crucial for achieving the best virological response. However, anaemia is a frequent, dose-dependent limiting side effect of ribavirin use. Therefore, therapeutic drug monitoring of ribavirin plasma concentrations could be a useful tool for individualizing ribavirin dosing. Herein, we review the relationship between ribavirin plasma concentrations and both virological response and toxicity, in order to define an optimal therapeutic range for ribavirin.

Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used as part of HIV therapy. Its favorable profile in terms of high efficacy, low toxicity and once-daily dosing makes TDF one of the most attractive antiretroviral agents, and therefore, it is widely used. However, cases of kidney tubular dysfunction have been reported and concern exists regarding the long term use of TDF. Owing to the high interindividual variability in the presentation of kidney function abnormalities, research has recently focused on host genetic factors predisposing to TDF-associated renal dysfunction. Transporter proteins involved in the renal elimination of TDF, such as organic anion transporter 1 or multidrug resistant protein 2 or 4, seem to be involved importantly and several genetic polymorphisms in these proteins have been associated with an increased risk of kidney tubulopathy in patients treated with TDF. In this review, all relevant pharmacogenetic factors that may play a role in the risk of renal toxicity associate...

Atazanavir use is associated with increases in serum bilirubin. Ribavirin, used to treat hepatitis-C infection, cause hemolysis and may worsen hyperbilirubinemia. We studied HIV/hepatitis-C virus-coinfected patients who initiated hepatitis-C therapy. Hyperbilirubinemia grade 3–4 increased from 9% to 45% after the start of hepatitis-C treatment in patients who used atazanavir concomitantly. Atazanavir use and hemoglobin (Hb) drops were predictors of increases in bilirubin. A substantial proportion of patients under atazanavir-therapy experienced significant hyperbilirubinemia and jaundice following initiation of hepatitis-C therapy.

To study the correlation between the HLA-B*5701 allele and the single nucleotide polymorphism in HCP5 (rs2395029). All HIV patients naive for abacavir seen at our institution between September 2007 and December 2008 were prospectively screened for HLA-B*5701. HCP5 rs2395029 genotyping was carried out by allelic discrimination using the TaqMan 5′-nuclease assay. High-resolution HLA class I typing was undertaken using sequence-specific primers. A total of 245 HIV patients were included in the study. A good correlation between HLA-B*5701 and HCP5 was observed (negative and positive predictive values of 100% and 93%, respectively). The use of HCP5 rs2395029 testing could be as useful as HLA-B*5701 typing to prevent the abacavir hypersensitivity reaction. Given that HCP5 testing is cheaper, less time-consuming and easier to perform than HLA typing, it may confidently replace the latter in clinical settings.

The influence of ribavirin trough concentrations (RBVC_trough) on the risk of hepatitis C virus (HCV) relapse was retrospectively analyzed in 99 HIV-HCV-coinfected patients who achieved end-of-treatment response with pegylated alpha interferon plus weight-based RBV. The independent predictors (odds ratio [OR] [95% confidence interval (CI)]) of HCV relapse were RBV plasmaC_troughof <2.5 μg/ml (4.5 [1.3 to 15.5]), baseline serum HCV RNA (2.5 [1.2 to 5.1]), and HCV genotype 1 or 4 (13.3 [2.6 to 66.7]). Monitoring of RBVC_troughmay permit early adjustment of RBV dosage to avoid HCV relapse.