title: Low body weight in females is a risk factor for increased tenofovir exposure and drug-related adverse events.
abstract: Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p = 0.003) and body weight (p = 0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight<50 kg had significantly higher plasma tenofovir concentrations than those weighting >50 Kg (160±93 vs.71±52 ng/mL, p<0.001). High tenofovir plasma trough concentrations and the age of the patients were independently associated with the development of drug-related kidney and bone toxicity. In this retrospective study we have shown that HIV-infected women with low body weight are at risk to be exposed to high tenofovir plasma trough concentrations, ultimately resulting in a significant hazard to develop long-term tenofovir complications.
authors: Department of Infectious Disease, L. Sacco University Hospital, Milan, Italy.
authors: Cristina
authors: C
authors: Gervasoni
authors: Paola
authors: P
authors: Meraviglia
authors: Simona
authors: S
authors: Landonio
authors: Sara
authors: S
authors: Baldelli
authors: Serena
authors: S
authors: Fucile
authors: Laura
authors: L
authors: Castagnoli
authors: Emilio
authors: E
authors: Clementi
authors: Agostino
authors: A
authors: Riva
authors: Massimo
authors: M
authors: Galli
authors: Giuliano
authors: G
authors: Rizzardini
authors: Dario
authors: D
authors: Cattaneo
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001835:Body Weight / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012307:Risk Factors; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine