No abstract

ObjectivesDespite the recent publication of case reports describing various manifestations of tenofovir-related nephrotoxicity, data regarding the incidence of and risk factors for this adverse effect are currently lacking. MethodsA retrospective cohort study of patients from four centres in Toronto, Canada, enrolled in the tenofovir expanded access programme with a minimum of 3 months follow up, was carried out. ResultsA total of 172 patients receiving tenofovir disoproxil fumarate (TDF) for a median of 16 months (range 3-25 months) were included in the study. Seven (4%) patients developed grade 1 (444 mmol/ L from baseline) increases in serum creatinine (SCr) during follow up; no patient developed grade 2 or higher nephrotoxicity. Fifteen (8.7%) patients had an increase in SCr of greater than 1.5 times baseline values during follow up. Four (2.3%) patients discontinued TDF because of an increase in SCr and/or abnormal urinalysis. Of 62 patients with a urinalysis, grade 1 or higher proteinuria (o 3 g/L) was observed in 27 (43%) patients. Only baseline SCr [odds ratio (OR) 5 0.51 per 10 mmol/L increase; P 5 0.0005] and baseline creatinine clearance (1.26 per 10 mL/min increase; P 5 0.01) were significantly associated with ever having a 1.5-fold increase in serum creatinine. Twenty-eight (16%) and 11 (6%) patients developed grade 1 (serum phosphorus 0.71 mmol/L) and grade 2 (serum phosphorus 0.61 mmol/L) hypophosphataemia during follow-up, respectively. ConclusionsAlthough slight increases in SCr did occur after starting TDF, clinically significant nephrotoxicity was rare. The clinical significance of TDF-related hypophosphataemia and proteinuria requires further study.Keywords: adverse effects, anti-HIV agents, creatinine, kidney, tenofovir IntroductionTenofovir disoproxil fumarate (TDF) is the only nucleotide analogue currently available for the management of HIV infection. The efficacy of TDF was initially established in two clinical trials with antiretroviral (ARV)-experienced patients, in which the addition of TDF to stable background therapy resulted in a significant decrease in viral load relative to placebo, with a similar incidence of adverse effects [1]. In addition, study GS-903 established TDF as a comparable alternative to stavudine when used in combination with lamivudine and efavirenz in ARV-naive patients, while eliciting less mitochondrial and metabolic toxicity [2]. The convenience of once-daily administration coupled with a favourable toxicity profile has rendered TDF a welcome addition to the ARV arsenal. Importantly, unlike structurally related nucleotide analogues such as cidofovir and adefovir, clinically significant nephrotoxicity did not emerge as a treatment-limiting adverse effect of TDF in the clinical trials. Furthermore, the renal safety profile of TDF was similar to that of stavudine over 144 weeks of followup in study However, post-marketing experience with TDF has raised the possibility that nephrotoxicity may be an uncommon but important adverse effect of this agent. Several c...

No abstract

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted.