Frédéric-Antoine Dauchy

Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy

Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.

Cognitive disorders in HIV-infected patients: are they HIV-related?

Objectives:Large unselected studies on representative samples of HIV-infected patients with a whole battery of neuropsychological tests and cerebral MRI scan are required to assess the frequency of neurocognitive impairment (NCI), the determinants of mild neurocognitive disorders (MNDs), or HIV-associated dementia (HAD) and the relationship between NCI and MRI scan findings. Methods:Investigation of 400 consecutively enrolled HIV-1-infected adults from the ANRS CO3 Aquitaine Cohort, using standardized neurocognitive tests chosen to achieve consistency with Frascatis criteria. Half of the patients had a cerebral MRI scan allowing gray and white matter volume measurement. Factors associated with NCI were studied by logistic regression models. Results:Median age of participants was 47 years, 79% were male and 89% received combination antiretroviral treatment (cART), of whom 93% had plasma HIV RNA below 500u200acopies/ml. Median CD4 cell count was 515 cells/&mgr;l. Prevalence of NCI was 59%, including 21% of asymptomatic NCI, 31% of MND, and 7% of HAD. A low level of education, prior neurologic AIDS-defining disorders event, anxiety, depressive symptoms, and prior history of brain damage were independently associated with MND or HAD, but neither HIV nor cART-related variables. The presence of NCI was significantly associated with lower gray matter fraction. Interpretation:In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with gray matter atrophy at early stages of the disease.

High frequency of poor locomotor performance in HIV-infected patients.

Objectives:To provide up-to-date assessments of locomotor function in HIV-infected patients and to identify potential determinants of impaired function. Design:Cross-sectional study in 324 HIV-1-infected adults from the French Agency for AIDS and Hepatitis Research (ANRS) CO3 Aquitaine Cohort using standardized locomotor tests. Methods:Patients underwent standardized testing assessing balance, walking ability, functional capacity and lower limb muscle performance. Poor test performance was defined by cut-offs based on age-specific data of the general population. Factors associated with poor test performance were studied by logistic regression. Results:Median age was 48 years, 80% were men and 89% were on antiretroviral treatment. The most frequently altered locomotor test was the five-times sit-to-stand (5STS) test, assessing lower limb muscle performance (poor performance: 53%). In multivariable analysis, time since HIV diagnosis was associated with poor 5STS performance [odds ratio (OR) = 1.08 per year; 95% confidence interval (CI): 1.03, 1.13]. In patients below 30 years, elevated BMI was associated with higher likelihood of good performance (OR = 0.81 per kg/m2; 95% CI: 0.69, 0.93), whereas in those above 70 years this association was reversed (OR = 1.30 per kg/m2; 95% CI: 1.10, 1.53; P < 10−3 for interaction). We found no association with antiretroviral treatment. Conclusion:One of two adults with controlled HIV infection had poor lower limb muscle performance, which might put this population at risk of falls and fracture. The 5STS test is a simple test that should be recommended to assess muscular performance in HIV care.

Role of Traditional Risk Factors and Antiretroviral Drugs in the Incidence of Chronic Kidney Disease, ANRS CO3 Aquitaine Cohort, France, 2004–2012

Objective To examine the role of antiretroviral drugs (ART), HIV-related and traditional risk factors on the incidence of chronic kidney disease (CKD) in HIV-infected patients. Design Prospective hospital-based cohort of HIV-infected patients from 2004 to 2012. Methods CKD was defined using MDRD equation as an estimated glomerular filtration rate (eGFR) less than 60 ml/mn/1.73 m2 at 2 consecutive measurements ≥3 months apart. Poisson regression models were used to study determinants of CKD either measured at baseline or updated. ART exposure was classified as ever or never. We additionally tested the role of tenofovir (TDF), whether or not prescribed concomitantly with a Protease Inhibitor (PI), taking into account the cumulative exposure to the drug. Results 4,350 patients (74% men) with baseline eGFR>60 ml/mn/1.73 m2 were followed for a median of 5.8 years. At the end of follow-up, 96% had received ART, one third of them (35%) jointly received TDF and a PI. Average incidence rate of CKD was 0.95% person-years of follow-up. Incidence of CKD was higher among women (IRRu200a=u200a2.2), older patients (>60 y vs <45 y: IRRu200a=u200a2.5 and 45–60 y: IRRu200a=u200a1.7), those with diabetes (IRRu200a=u200a1.9), high blood pressure (IRRu200a=u200a1.5), hyperlipidemia (IRRu200a=u200a1.5), AIDS stage (IRRu200a=u200a1.4), low baseline eGFR (IRRu200a=u200a15.8 for 6090 and IRRu200a=u200a7.1 for 70500/mm3 (IRRu200a=u200a2.5), and exposure to TDF (IRRu200a=u200a2.0). Exposure to TDF was even strongly associated with CKD when co-administered with PIs (IRRu200a=u200a3.1 vs 1.3 when not, p<0,001). A higher risk of CKD was found when tenofovir exposure was >12 months [IRRu200a=u200a3.0 with joint PIs vs 1.3 without (p<0.001)]. A vast majority of those developing CKD (76.6%) had a baseline eGFR between 60 and 80 ml/mn/1.73 m2. Conclusion In patients with eGFR between 60 and 80 mL/min/1.73 m2, a thorough control of CKD risk factors is warranted. The use of TDF, especially when co-administered with PIs, should be mentioned as a relative contraindication in presence of at least one of these risk factors.