RESUMEN
OBJECTIVE: To assess if tenofovir (TFV) clearance is associated with urinary retinal-binding protein (RBP) in HIV-positive patients with normal estimated filtration rate. DESIGN: A cross-sectional diagnostic study. METHODS: HIV-positive patients with estimated creatinine clearance above 60âml/min, on tenofovir disoproxil fumarate (TDF)-containing combination since at least 6 months, taking TDF at night, and without significant comorbidities (diabetes, untreated hypertension, known renal malformations, recurrent nephrolithiasis) and nephrotoxic drugs were included. TFV plasma and urinary concentrations were measured 12âh after drug intake (C12). RBP was measured through enzyme immunoassay kit on spot urines and corrected per urinary creatinine (uRBP/uCr); normality ranges were below 130âµg/g (in patients aged <50 years) and below 172âµg/g (in patients aged ≥50 years). RESULTS: Two hundred and eighty-nine patients were included (median age of 45.8 years, 71.6% male and 85.4% whites); patients were concomitantly treated with nonnucleoside reverse transcriptase inhibitors (155, 53.6%), protease inhibitors (118, 40.8%), or integrase inhibitors (16, 5.5%)-containing regimens. Estimated creatinine clearance was 89.4âml/min (78.6-105.9). Urinary RBP (uRBP) and uRBP/uCr were 204.6âng/ml (92-380) and 169.7âµg/g (85.8-318.3), respectively; abnormally high uRBP/uCr was observed in 157 patients (54.3%). A multivariate binary logistic regression confirmed that both ethnicity (Pâ=â0.004, ß 2.93, 95% confidence interval 1.41-6.10) and TFV urinary C12 less than 21âmg/ml (Pâ=â0.006, ß 2.04, 95% confidence interval 1.12-3.41) were significantly associated with abnormal uRBP/uCr. CONCLUSION: HIV-positive TDF-treated patients showed a high prevalence of proximal tubular impairment: ethnicity (whites) and low urinary TFV concentrations were significantly associated with elevated uRBP. SDC VIDEO:: http://links.lww.com/QAD/A852.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Insuficiencia Renal/patología , Tenofovir/farmacocinética , Adulto , Fármacos Anti-VIH/administración & dosificación , Enfermedades Asintomáticas , Estudios Transversales , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Plasma/química , Tenofovir/administración & dosificación , Orina/químicaAsunto(s)
2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Rilpivirina/farmacocinética , Interacciones Farmacológicas , Humanos , Cirrosis Hepática/metabolismo , Masculino , Persona de Mediana Edad , PantoprazolRESUMEN
The aim of this study was to evaluate the impact of HIV-1 very low-level viremia (<50 copies/ml) on the 2-year risk of virological failure. A retrospective analysis including HIV-positive patients presenting two consecutive HIV RNA below 50 copies/ml (outpatient clinic in Italy, first semester of 2010) was performed. HIV RNA was measured through real time polymerase chain reaction (PCR) assay CAP/CTM HIV-1 version 2.0 (detection limit: 20 copies/ml) and stratified as undetectable RNA ("Target Not Detected", TND), <20 copies/ml, 20-50 copies/ml. After 96 weeks virological failure was defined as two consecutive viral loads above 50 copies/ml. Log-rank tests and a multivariate Cox proportional hazard model were used for univariate and multivariate analysis. A total of 1,055 patients (71.4% male, 87.4% white, aged 46.7 years) were included: nadir and current CD4 cell counts were 203 cells/mm(3) (106-292) and 554 cells/mm(3) (413-713.5). HIV RNA was undetectable in 781 patients (74%), <20 copies/ml in 190 patients (18%) and 20-50 copies/ml in 84 patients (8%). Virological failure was observed in 81 patients (7.7%); at multivariate analysis detectable RNA at baseline (p=0.017), HCV infection (p=0.020), more than three pills in the regimen (p=0.003), and duration of HIV RNA <50 copies/ml below 2 years (p<0.001) were independently associated with virological failure. In 14 patients newly selected resistance-associated mutations were observed. Undetectable HIV RNA by real-time PCR is significantly associated with a lower 2-year risk of virological failure along with Ab HCV negativity, longer viral control, and lower pill burden. Studies investigating the management of residual viremia under antiretroviral treatment are warranted.