Tenofovir clearance is reduced in HIV-positive patients with subclinical tubular impairment.

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 60 ml/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 12 h 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 130 µg/g (in patients aged <50 years) and below 172 µg/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 89.4 ml/min (78.6-105.9). Urinary RBP (uRBP) and uRBP/uCr were 204.6 ng/ml (92-380) and 169.7 µg/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 (P = 0.004, ß 2.93, 95% confidence interval 1.41-6.10) and TFV urinary C12 less than 21 mg/ml (P = 0.006, 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.

HIV-1 Very Low Level Viremia Is Associated with Virological Failure in Highly Active Antiretroviral Treatment-Treated Patients.

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.