Incidence of proximal renal tubular dysfunction in patients on tenofovir disoproxil fumarate

Abstract

The concern about the specificity of nucleic acid amplification tests (NAATs) in low prevalence GC populations is associated with its false positivity (cross-reactions with different Neisseria species) impacting on positive predictive value. Not all NAATs are the same and this type of false positivity has not been observed with AC2 to date. 2,3 In Cheshire and Merseyside, UK, we have since 2004 incorporated dual testing for chlamydia (CT) and GC into our chlamydia screening programmes using the Gen-Probe Aptima Combo 2 assay (AC2).Lavelle et al. in the Liverpool and South Sefton Chlamydia Screening Programme showed that, in those under age 25, a total of 55 cases of GC would have been missed if tested only for CT (47/4680(1%) of women and 8/473(1.7%) of men. Of the 47 women positive for GC, more than half, 26 (55%) were negative for CT. The CT prevalence in their population was 12% and 15.7% for women and men, respectively. 4 Our recent article in this journal showed that dual testing in the community contributed substantially to the overall number of GC cases found -40 community cases versus 35 at Macclesfield Genitourinary (GU) Medicine clinic. The overall prevalence of GC in the GU medicine clinic was 1.3% (true prevalence 0.9% on primary test) and that in the community was 0.4%. In the asymptomatic chlamydia screening population aged 15 -24 years, community tests made a total contribution of 32 cases (9/1330 [0.67%] men and 23/5070 [0.45%] women). 3 These 32 cases would have gone undiagnosed and untreated for GC within the community if the NAAT performed had been for CT alone. In our study too, the majority of the GC cases (.60%) were found in those with a negative result for CT. 5 Both of the above studies 4,5 thus show that dual testing at the outset would find more GC infections than reflex testing of CT positives.The Cheshire and Merseyside Sexual Health network already recommends concomitant screening for CT and GC using AC2 in asymptomatic low-risk individuals. 6 Publications from this region 5,7,8 have already shown that AC2 picks up extra cases of GC over and beyond culture in GU medicine clinics. The pick up of extra cases of GC at extragenital sites by AC2 has been reported by us and others. 5,9,10 Even in low prevalence populations we have demonstrated the opportunity to pick up substantial additional numbers of GC cases beyond those detected by current services. 11 The accumulating evidence shows that consideration of incorporating dual testing for CT and GC by the NCSP is long overdue and a wider consideration of application of GC NAATs should be considered.

The Incidence and Clinical Characteristics of Acute Serum Creatinine Elevation more than 1.5 mg/dL among the Patients Treated with Tenofovir/Emtricitabine-containing HAART Regimens

“…First, four patients (2.9%) in our study had serum Cr levels that increased more than 1.5 mg/dL during HAART. Other study that treated 10,000 HIV-infected patients with TDF and monitored the increase in serum Cr found that 2.2% of cases showed baseline serum Cr more than 0.5 mg/dL and 0.6% increased more than 2.0 mg/dL [ 8 ], which was similar to our results. Second, the four patients whose serum Cr increased more than 1.5 mg/dL were administered both TDF and a PI/r drug.…”

“…Nephrotoxicity can appear either during long or short-term use of TDF. TDF-induced nephrotoxicity is reported in about 15% of patients treated with TDF for 2-9 years [ 8 ]. Previous studies have reported several risk factors for TDF-induced nephrotoxicity, including high basal serum creatinine (Cr) level, concomitant use of nephrotoxic drugs, low body weight, old age, and low CD4+ T cell count [ 9 ].…”

Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney

“…Numerous case reports and case series have described severe cases of renal tubular toxicity associated with TDF exposure [3-5]. It is estimated that renal tubular dysfunction develops in nearly 15% of patients treated with tenofovir for 2–9 years [6]. Tubular dysfunction may precede the decline of renal function [7].…”

Postexposure prophylaxis, preexposure prophylaxis or universal test and treat: the strategic use of antiretroviral drugs to prevent HIV acquisition and transmission

“…For example, long-term use of TDF is associated with risk of renal tubular dysfunction [80][81][82]. ART is not currently an over-the-counter medicine.…”