The aim of the study was to investigate the prevalence and aetiology of chronic kidney disease (CKD) and trends in estimated glomerular filtration rate (eGFR) in HIV-infected patients. MethodsAscertainment and review of CKD cases among patients attending King's College and Brighton Hospitals, UK were carried out. CKD was defined as eGFR o60 mL/min for ! 3 months. Longitudinal eGFR slopes were produced to examine trends in renal function before, during and after exposure to indinavir (IDV) or tenofovir (TFV). ResultsCKD prevalence was 2.4%. While HIV-associated nephropathy accounted for 62% of CKD in black patients, 95% of CKD in white/other patients was associated with diabetes mellitus, hypertension, atherosclerosis and/or drug toxicity. Exposure to IDV or TFV was associated with an accelerated decline in renal function (4.6-fold and 3.7-fold, respectively) in patients with CKD. In patients initiating IDV, age ! 50 years increased the odds of CKD [odds ratio (OR) 4.9], while in patients initiating TFV, age ! 50 years (OR 5.4) and eGFR 60-75 mL/min (OR 17.2) were associated with developing CKD. ConclusionThis study highlights the importance of metabolic and vascular disease to the burden of CKD in an ageing HIV-infected cohort. In patients who developed CKD, treatment with IDV or TFV was associated with an accelerated decline in renal function.Keywords: glomerular filtration rate, HIV, indinavir, kidney, tenofovir Accepted 20 November 2008 Introduction Acute renal failure (ARF) and chronic kidney disease (CKD) are important complications of HIV infection [1]. Approximately 6% of HIV-infected patients develop one or multiple episodes of ARF [2], and 15% of patients have evidence of CKD [3,4]. ARF usually occurs in the setting of severe (opportunistic) infections, malignancy or liver disease [2,5], and both ARF and CKD are associated with advanced immunodeficiency [2][3][4][5][6]. Black HIV-infected patients are at risk of developing HIV-associated nephropathy (HIVAN), which is characterized by heavy proteinuria and rapid progression to end-stage renal disease (ESRD) [7][8][9]. HIVAN, idiopathic noncollapsing focal and segmental glomerulonephritis (FSGS), immune complex kidney disease and other glomerulopathies predominate in biopsy series and among black patients with ESRD [7,[10][11][12][13].In the general, HIV-uninfected population, the prevalence of CKD increases dramatically in those aged 50 years and over [14]. CKD in these patients is associated with diabetes mellitus, hypertension and atherosclerosis [15], and is an independent risk factor for coronary heart disease [16]. CKD in this setting is often insidious in onset and may take decades to become clinically manifest. The objectives of this study were to describe the prevalence and aetiology of CKD in HIV-infected patients receiving care in the UK, and to examine trends in renal function before, during and after exposure to IDV or TFV in patients with CKD. Methods Case ascertainmentAll HIV-infected adults with CKD who attended King's College Hospital ...

Word count: 247 (max 250) ObjectivesWhilst cognitive impairment is frequently reported in HIV-positive individuals and has historically been associated with poorer functional outcomes, the associations between cognitive impairment and patient-reported outcome measures (PROMs) in contemporary cohorts are unclear. MethodsWe tested cognitive function using a computerised battery (

ObjectivesThe single‐tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV‐1‐infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF.MethodsWe conducted two distinct randomized, double‐blind, active‐controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each study randomized virologically suppressed (HIV‐1 RNA < 50 copies/mL) adults (1:1) to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We evaluated efficacy as the proportion with HIV‐1 RNA < 50 copies/mL using the Food and Drug Administration snapshot algorithm and prespecified bone and renal endpoints at week 96.ResultsWe randomized and treated 630 participants in Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160 (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval (CI) −4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI −4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment‐emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with continuing baseline therapy, significant improvements in bone mineral density and renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001).ConclusionsSwitching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe and effective and improved bone mineral density and renal biomarkers up to 96 weeks with no cases of treatment‐emergent resistance.

1Objectives: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV 2 and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We 3 aimed to study the risk factors for developing severe renal tubulopathy. 4 Methods:We conducted an observational cohort study with retrospective identification of cases of 5 treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression 6 analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted 7 estimated glomerular filtration rate (eGFR) slopes. 8

Objective:The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study.Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n ϭ 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results:The median (interquartile range) CPE score for initial cART regimen increased from 7(5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in [2006][2007][2008]. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores Յ4, and less frequently in those with scores Ն10; however, these differences were nonsignificant. Initial and most recent cART CPE scores Յ4 were independently associated with increased risk of death. Conclusion:Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. Neurology ® 2011;76:693-700