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Purpose of Review: This review examines the impact of HIV on kidney disease, which remains significant despite advances in antiretroviral therapy (ART). The review is timely due to the shifting epidemiology of kidney disease in people with HIV (PWH), driven by increased ART access, noncommunicable diseases, and region-specific opportunistic infections like tuberculosis., Recent Findings: The literature highlights a decline in HIV-associated nephropathy (HIVAN) and a rise in tubulointerstitial diseases and noncommunicable diseases among PWH. Studies from the United States and South Africa report decreased HIVAN prevalence and increased rates of tubulointerstitial diseases linked to tenofovir disoproxil fumarate (TDF) toxicity and tuberculosis (TB). Immune complex glomerulonephritis (ICGN) and diabetic kidney disease (DKD) are also prevalent., Summary: The findings underscore the need for improved diagnostic tools for opportunistic infections, management of ART-related complications, and strategies to address noncommunicable diseases in PWH. There is a need to centralize care to address all health needs simultaneously. Future research should focus on APOL1-targeted therapies and the role of SGLT2 inhibitors in CKD. Enhanced transplantation outcomes and the development of guidelines for managing DKD in PWH are critical for advancing clinical practice and improving patient outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

HIV infection remains one of the leading causes of morbidity and mortality worldwide, especially in children living in resource-limited settings. Although the World Health Organization (WHO) recently recommended antiretroviral therapy (ART) initiation upon diagnosis regardless of the number of CD4, ART access remains limited, especially in children living in sub-Saharan Africa (SSA). HIV-infected children who do not receive appropriate ART are at increased risk of developing HIV-associated nephropathy (HIVAN). Although due to genetic susceptibility, SSA is recognized to be the epicenter of HIVAN, limited information is available regarding the burden of HIVAN in children living in Africa. The present review discusses the information available to date on the prevalence, pathogenesis, risk factors, diagnosis, and management of HIVAN in children, focusing on related challenges in a resource-limited setting., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Although antiretroviral therapy (ART) has increased life expectancy in people with HIV-1 (PWH), acute and chronic kidney disease remain common in this population and are associated with poor outcomes. A broad spectrum of kidney disorders can be observed in PWH, some of which are directly related to intrarenal HIV infection and gene expression. HIV-associated nephropathy (HIVAN) was the most common kidney disease in PWH before ART became available. Animal models and human biopsy studies established the causal relationships between direct HIV-1 infection of renal epithelial cells and HIVAN, expression of viral genes in renal epithelial cells, and dysregulation of host genes involved in cell differentiation and cell cycle. In this review, we provide a summary of the body of work demonstrating HIV-1 infection of epithelial cells in the kidney and recent advancements in the understanding of viral entry mechanisms and consequences of HIV-1 gene expression in those cells., (© 2023. The Author(s).)

Introduction: Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country., Methods: DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve., Results: The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group., Conclusion: This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG., Competing Interests: NO authors have no competing interests

Four decades after the first cases of HIV were reported, kidney disease remains an important comorbidity in people with HIV (PWH). Both HIV-associated nephropathy and immune complex kidney disease were recognized as complications of HIV infection in the early years before treatment was available. Although the introduction of effective antiretroviral therapy in the late 1990s resulted in dramatic improvements in survival and health in PWH, several commonly used antiretroviral agents have been associated with kidney injury. HIV infection and treatment may also promote the progression of comorbid chronic kidney disease due to traditional risk factors such as diabetes, and HIV is one of the strongest "second hits" for the high-risk APOL1 genotype. Unique considerations in the management of chronic kidney disease in PWH are largely related to the need for lifelong antiretroviral therapy, with potential for toxicity, drug-drug interactions, and polypharmacy. PWH who develop progressive chronic kidney disease are candidates for all modalities of kidney replacement therapy, including kidney transplantation, and at some centers, PWH may be candidates to serve as donors for recipients with HIV. Transplantation of kidney allografts from donors with HIV also offers a unique opportunity to study viral dynamics in the kidney, with implications for kidney health and for research toward HIV cure. In addition, HIV-transgenic animal models have provided important insights into kidney disease pathogenesis beyond HIV, and experience with HIV and HIV-related kidney disease has provided important lessons for future pandemics., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors., Methods: A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made., Results: One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4 +  T cells count < 200 cells/μL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7., Conclusions: Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible., (© 2021. The Author(s).)

HIV-associated nephropathy (HIVAN) predominantly affects people of African ancestry living with HIV who do not receive appropriate antiretroviral therapy (ART). Childhood HIVAN is characterized by heavy proteinuria and decreased kidney function. Kidney histology shows mesangial expansion, classic or collapsing glomerulosclerosis, and microcystic renal tubular dilatation leading to kidney enlargement. The pathogenesis of HIVAN involves the kidney recruitment of inflammatory cells and the infection of kidney epithelial cells. In addition, both viral and genetic factors play key roles in this disease. Modern ART has improved the outcome and decreased the prevalence of childhood HIVAN. However, physicians have had modest success providing chronic ART to children and adolescents, and we continue to see children with HIVAN all over the world. This article discusses the progress made during the last decade in our understanding of the pathogenesis and treatment of childhood HIVAN, placing particular emphasis on the mechanisms that mediate the infection of kidney epithelial cells, and the roles of cytokines, the HIV-Tat gene, and the Apolipoprotein-1 (APOL1) gene risk variants in this disease. In view of the large number of children living with HIV at risk of developing HIVAN, better prevention and treatment programs are needed to eradicate this disease.

Introduction: Human Immunodeficiency Virus (HIV) infects multiple tissues of the body, including the renal parenchyma, with HIV-associated Nephropathy (HIVAN) being the most common form of the HIV-related renal disease and an important cause of End Stage Renal Disease (ESRD) in HIV infected patients. There is paucity of studies on HIVAN among children with renal diseases, most studies on HIVAN focused on prevalence among HIV patients with vertical transmission being the commonest route. We undertook this study to determine the prevalence and impact of HIVAN among our renal patients and to highlight the new route of HIV transmission observed in these group of patients in Port Harcourt, Southern Nigeria., Materials and Methods: The study was conducted among renal patients managed in the Paediatric department of the University of Port Harcourt Teaching Hospital from December 2016 to March 2019. The information on the HIVAN patients were stored and retrieved from the renal register where all cases of renal diseases were enrolled. The diagnosis of HIVAN was made based on presence of significant proteinuria (≥ 1+), with one or more of the following: abnormal microscopic examination of urinary sediments, rising serum creatinine, renal ultrasound finding of enlarged echogenic kidneys and histology finding of focal segmental glomerulosclerosis. The patient's sociodemographic data, clinical presentation, route of transmission of HIV, laboratory investigations, treatment, and clinical outcome were obtained and analysed using SPSS version 25.0., Results: There were 112 cases of renal diseases seen during the study period of which 10 (8.9%) had HIVAN. The HIVAN patients were aged between 4-17years. Four (40%) of these HIVAN cases had CKD of which 2 (20%) had ESRD. The route of transmission of HIV was vertical (mother-to-child) in 8 patients and via sexual route in two older male patients aged 17years who were homosexuals. Mortality rate among the HIVAN patients was 30%, with 2 (20%) lost to follow up., Conclusion: There is a rising prevalence of HIVAN among paediatric patients with renal diseases in our environment, with homosexuality being a new route of HIV transmission observed in the older patients., Competing Interests: The author certifies that there is no conflict of interest in connection with the submitted article. All Conflict of Interest Forms are on file with the journal publication and are available on request., (Copyright © 2021 by West African Journal of Medicine.)

Background: HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD., Objectives: We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria., Methods: We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases., Results: Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches., Conclusion: Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine., Competing Interests: The authors have declared that no competing interests exist.

Clinical Background and Epidemiology: Worldwide, an estimated 38 million people are living with HIV infection. The classic kidney disease of HIV infection, commonly known as HIV-associated nephropathy, is a collapsing form of focal segmental glomerulosclerosis that almost exclusively affects individuals of African descent with advanced HIV disease. People living with HIV are also at risk for immune-complex kidney diseases, antiretroviral nephrotoxicity, and kidney disease due to co-infections and comorbidities. Challenges: The burden of HIV-related kidney disease is greatest in traditionally disadvantaged populations in resource-limited settings in sub-Saharan Africa and the Caribbean and among minority populations in the United States and Europe. Factors contributing to these disparities include a higher prevalence of HIV infection, limited access to optimal antiretroviral therapy, and genetic susceptibility to kidney disease. Treatment and Prevention: Current treatment guidelines recommend the initiation of life-long antiretroviral therapy in all people living with HIV to prevent AIDS and non-AIDS complications, including kidney disease. People living with HIV who progress to end-stage kidney disease despite treatment are candidates for dialysis and kidney transplant, including the possibility of accepting organs from HIV-positive donors in some settings. Although HIV prevention is currently the only definitive solution, expanding access to antiretroviral therapy, dialysis, and kidney transplantation in people living with HIV are important intermediate steps to address the global burden of HIV-related kidney disease., (© 2021 S. Karger AG, Basel.)

Introduction: End-stage renal disease (ESRD) related to HIV is becoming a leading cause of renal replacement therapy requirement is some areas of the world. Our study aims to describe the incidence and renal outcomes of HIV-associated nephropathy (HIVAN), and immune-mediated kidney disease related to HIV (HIVICK) in Colombia., Methodology: A retrospective cohort study was performed, including all HIVAN or HIVICK incident cases assessed by the infectious diseases division in a high complexity institution in Colombia, between 2004 and 2018. A longitudinal data model under the Generalized Estimating Equations (GEE) method was used to determine changes on the glomerular filtration rate (GFR) over time., Results: Within a cohort composed by 1509 HIV-infected patients, we identified 22 with HIV-associated glomerular disease. Cumulative incidence was 1.45%. At diagnosis, GFR was above 30 mL/min in 90.8% of patients, and 77.2% displayed sub-nephrotic proteinuria. Factors associated with GFR at diagnosis were: level of CD4 (Coefficient 0.113, CI 95 %: 0.046, 0.179, p < 0.01), and the inverse of the CD4/CD8 ratio. The GEE model did not demonstrate significant changes in the GFR over a 3-year period. Findings were similar when comparing GFR at diagnosis with GFR at 12 (-3.9 mL/min/1.73m2, CI 95% -7.3, 0.4, p = 0.98), 24 (-2.47 mL/min/1.73m2, CI 95% -7.0, 2.1, p=0.85), and 36 months (0.39 mL/min/1.73m2, CI 95% -4.4, 5.2, p = 0.43) of follow-up., Conclusions: Patients with glomerular disease associated with HIV have stable GFR over a 3-year period, and low rates of progression towards dialysis requirement. Differences with previous reports could be related with early diagnosis and treatment with highly active antiretroviral therapy., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Oscar Munoz-Velandia, Angel Garcia-Pena, Javier Garzon-Herazo, Kateir Contreras-Villamizar, Martha Rodriguez-Sanchez, Elias Garcia-Consuegra, Esteban Toro-Trujillo.)

HIV-associated kidney disease is evolving rapidly. Few North American studies have addressed modern trends and none has applied the 2018 Kidney Disease Improving Global Outcomes (KDIGO) pathologic classification. Therefore we performed a retrospective clinical-pathologic analysis of all HIV-positive patients with kidney biopsy interpreted at Columbia University from 2010-2018 using the KDIGO classification. The biopsy cohort of 437 HIV-positive patients had median age 53 years, including 66% males, 80% on anti-retroviral therapy, 57% with hypertension, 31% with diabetes, 27% with hepatitis C and 6% with hepatitis B co-infections. Race, known in 308 patients, included 58% black, 25% white and 17% Hispanic. Pathologic diagnoses were surprisingly diverse. Immune complex glomerulonephritis (ICGN) and diabetic nephropathy each outnumbered HIV-associated nephropathy, followed by tenofovir nephrotoxicity, FSGS- not otherwise specified (NOS) and global sclerosis (NOS). HIV-associated nephropathy was the most common disease in patients not on anti-retroviral therapy, and 94% were black. The association of FSGS (NOS) with black race (68%) and anti-retroviral therapy use (77%) suggests some cases may represent attenuated HIV-associated nephropathy. The most common ICGNs were IgA nephropathy and membranous glomerulopathy, both associating with anti-retroviral therapy (over 90%), followed by hepatitis C-associated proliferative ICGN. Among the 16 cases of uncharacterized ICGN lacking identifiable etiology, 69% were not on anti-retroviral therapy, possibly representing true HIV-associated immune complex kidney disease. Dual diseases occurred in 17% of patients, underscoring lesion complexity. Thus, anti-retroviral therapy has shifted the landscape of HIV-associated kidney disease toward diverse ICGN, diabetic nephropathy, and non-collapsing glomerulosclerosis, but has not eradicated HIV-associated nephropathy., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is a frequent complication of HIV infection. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is histologically the second most common diagnosis. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated overall improvement in kidney function with initiation of ART. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. HIV-positive patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV-positive patients; graft and patient survival is similar to that of HIV-negative recipients. Early detection of kidney disease by implementation of screening on diagnosis of HIV infection and annual screening thereafter will have an impact on the burden of disease, together with access to ART. Programs for prevention of HIV infection are essential.

Objectives: The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the interaction of the effects of aging, baseline renal impairment, and stages of HIV infection on post-treatment changes in renal function., Methods: This analysis included 5533 HIV-infected patients on cART in 2004-2016. Progression to chronic kidney disease (CKD) was defined as either two consecutive estimated glomerular filtration rate (eGFR) measurements < 60 mL/min/1.73 m 2 for baseline eGFR ≥ 60 mL/min/1.73 m 2 (mild renal impairment or normal renal function) or a 25% decline for baseline eGFR < 60 mL/min/1.73 m 2 (moderate renal impairment)., Results: During follow-up (median 4.8 years), 130 (2.3%) of the patients progressed to CKD. A total of 20.1% of patients with baseline normal renal function progressed to mild renal impairment, while 74.0% of patients with baseline mild or moderate renal impairment improved to normal renal function. In multivariable analysis, a significant positive baseline-eGFR-by-World Health Organization (WHO)-stage interaction effect on progression to CKD in all patients was identified, indicating a cross-over effect from a reduced risk to an increased risk. A significant negative baseline-age-by-WHO-stage interaction effect on progression to mild renal impairment in patients with baseline normal renal function was identified, with adjusted hazard ratios progressively lower at older ages. In addition, there were significant associations with older age, lower baseline eGFR, Dai ethnic minority, and anaemia for both outcomes, hyperglycaemia for CKD only, and higher CD4 count, tenofovir and ritonavir-boosted lopinavir use for mild renal impairment only., Conclusions: Our data suggest a complex pattern of renal function dynamics in patients on cART, which requires precise management with systematic monitoring of the interaction of the effects of sociodemographic, nephrological and HIV-specific clinical characteristics., (© 2019 British HIV Association.)

The kidney is an important target organ in human immunodeficiency virus (HIV) infection, and a variety of renal disorders could occur throughout the course of the disease. HIV- associated nephropathy (HIVAN) is the most common form of kidney disease resulting directly from HIV infection. The true prevalence of HIVAN among infected African children is unknown largely due to lack of surveillance and reporting. We thus aimed to determine the prevalence of HIVAN and associated factors among HIV-infected children at the University of Maiduguri Teaching Hospital. This was a cross-sectional study carried out at the Pediatric Infectious Clinic. Children aged ≤15 years were recruited through systematic random sampling. Relevant sociodemographic and clinical information were obtained. Spot urine sample was analyzed using a multistix (Combi-Screen 10SL Analyticon Biotechnologies AG, Germany), and proteinuria of ≥2+ was considered significant. The CD4+ count and CD4+% (for those <5 years) were obtained using a PARTEC™ CD4+ easy count kit. The obtained data were entered and analyzed using Statistical Package for the Social Sciences version 16.0. A total of 250 children were recruited. Eighty-five (34%) of them had HIVAN. Sex, social class, and mode of transmission were not significantly associated with HIVAN (P >0.05). However, age, medication status (highly active antiretroviral therapy [HAART]), duration on HAART, and disease severity (both clinical and immunological) all had a significant association to HIVAN (p = 0.005, 0.004, 0.008, and <0.001, respectively). These factors also showed a positive but weak correlation to HIVAN; while age had the least correlation coefficient (0.157), immunological class had the highest r = 0.458. However, these relationships were all significant (P <0.5). HIVAN is highly prevalent among children living with HIV in Maiduguri. Routine screening through urina-lysis and early commencement of HAART is recommended., Competing Interests: None

Background: The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy., Methods: All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months., Results: Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m 2 vs. 47 mls/min/1.73m 2 , p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071)., Conclusions: In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required., Trial Registration: ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

Background: In the era of combined antiretroviral therapy, classic focal segmental glomerulosclerosis (FSGS) is the most common histopathological finding in African American HIV-positive patients with kidney disease. We sought to determine whether HIV suppression is associated with lower risk of progression to end-stage renal disease (ESRD) among HIV-positive African Americans with biopsy-confirmed classic FSGS., Methods: HIV-positive African Americans who underwent kidney biopsies at a single tertiary hospital between January 1996 and June 2011 were confirmed as having classic FSGS by the presence of segmental glomerulosclerosis without features of HIV-associated nephropathy. Multivariable Cox proportional hazards models were used to examine the independent association of viral suppression (HIV-RNA < 400 copies per milliliter at biopsy) with time to progression to ESRD., Results: Of the 55 HIV-positive African Americans with classic FSGS, 26 had suppressed viral loads at the time of biopsy. Compared to viremic patients, those who were virally suppressed had a significantly higher mean CD4 cell count (452 vs. 260 cell/mm, respectively; P = 0.02) and median estimated glomerular filtration rate (53.5 vs 35.5 mL/min/1.73 m, respectively; P = 0.002). Adjusting for sex and baseline CD4 cell count, estimated glomerular filtration rate, and proteinuria, those with HIV-RNA levels <400 copies per milliliter at baseline had a 75% lower risk of progressing to ESRD (hazard ratio = 0.25; 95% CI: 0.07 to 0.88) during a median follow-up time of 2.70 years (interquartile range: 0.80-5.15 years)., Conclusions: HIV suppression is associated with significantly lower risk of progression to ESRD among HIV-infected African Americans with classic FSGS, supporting the potential role of combined antiretroviral therapy for this histopathology in addition to HIV-associated nephropathy among HIV-positive individuals.

Objective: The current study aimed to validate existing risk prediction scores and identify predictors of chronic kidney disease (CKD) in the setting of HIV., Design and Methods: A retrospective cohort study of HIV-positive individuals (n = 748) with baseline estimated glomerular filtration rate (eGFR) more than 60 ml/min was conducted at the Alfred Hospital, Melbourne, Australia. Multivariable regression analysis was performed to determine factors associated with development of CKD, defined as two consecutive measurements of eGFR less than 60 ml/min. The performance of CKD risk scores proposed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group and Scherzer and colleagues were estimated by the area under the receiver operator curve (AUROC)., Results: CKD developed in 37 individuals (5.0%), at a median of 4.7 (interquartile range 2.2, 6.2) years. Older age [odds ratio (OR) 3.03, 95% confidence interval (CI): 1.20, 7.65, P = 0.02] and lower baseline eGFR (OR 10.39, 95% CI: 4.73, 22.83, P < 0.001) were associated with the development of CKD. Neither current, nor cumulative tenofovir disoproxil fumarate (TDF) use was associated with progression to CKD [current TDF hazard ratio (HR) 1.05, 95% CI: 0.54, 2.07, P = 0.88; cumulative TDF HR 1.03, 95% CI: 0.86, 1.24, P = 0.75]. The short D:A:D and Scherzer scores were well calibrated, with the short D:A:D score demonstrating superior discrimination (short D:A:D AUROC 0.85, Scherzer AUROC 0.78, P = 0.02)., Conclusion: Older individuals and those with a lower baseline eGFR are at higher risk for CKD. Risk prediction tools may be useful in identifying those at greatest risk, who may benefit from aggressive management of risk factors.

Aim: The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population., Methods: AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 March 2016 and an initial estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m 3 . Cox proportional hazards models were used to assess risk factors for CKD, which included key patient demographic data and antiretroviral therapy (ART) exposure., Results: Of 1924 patients included in the analysis between April 2008 and March 2016, 81 (4.2%) developed CKD (confirmed eGFR of less than 60 mL/min per 1.73 m 3 through two consecutive eGFR measurements at least 3 months apart). Of the examined risk factors, baseline age, baseline eGFR, and the route of HIV acquisition were statistically significant predictors of development of CKD. ART exposure, viral hepatitis co-infection, high viral load and low CD4 lymphocyte count were not found to be significant risk factors for CKD., Conclusion: This is the first study to investigate the risk factors for development of CKD among Australian HIV-infected patients using cohort data. It highlights the need for awareness of renal risk factors, particularly among older patients or in those with pre-existing renal dysfunction. Further research is required to explore the discrepancy between patients who have acquired HIV through different means of exposure., (© 2017 Asian Pacific Society of Nephrology.)

Purpose of Review: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) was identified as the major renal manifestation of HIV infection early in the HIV epidemic. However, HIV infection now is associated with a different spectrum of renal lesions leading to chronic kidney disease. This review examines the changes in kidney injury occurring in the current HIV era and the factors involved in this transformation of disease expression., Recent Findings: The incidence of HIVAN and opportunistic infections in HIV-infected individuals has declined in concert with the use of effective combination antiretroviral agents. Chronic kidney disease has become more prevalent as patients infected with HIV are living longer and developing non-HIV-associated diseases such as hypertension and diabetes. Additionally, noncollapsing focal and segmental glomerulosclerosis, co-infection with hepatitis C, HIV-associated immune complex kidney disease, HIV-related accelerated aging, and antiretroviral therapies contribute to progressive loss of renal function., Summary: HIV infection is now associated with a variety of renal lesions causing chronic kidney disease, not all of which are virally induced. It is important to determine the cause of renal functional decline in an HIV-infected patient, as this will impact patient management and prognosis.

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Human immunodeficiency virus (HIV) infection continues to be a leading cause of morbidity and mortality. HIV-infected individuals are now surviving for a relatively longer period and this is because of easy accessibility to antiretroviral therapy these days. As a result, chronic disease-related complications are now being recognized more often. Kidney disease in HIV-infected children can vary from glomerular to tubular-interstitial involvement. We searched the database to identify various kidney diseases seen in HIV-infected children. We describe the epidemiology, pathogenesis, pathology, clinical and laboratory manifestations, management and outcome of commonly seen kidney disease in HIV-infected children. We also provide a brief overview of toxicity of antiretroviral drugs seen in HIV-infected children. Kidney involvement in HIV-infected children may arise because of HIV infection per se, opportunistic infections, immune mediated injury and drug toxicity. HIV-associated nephropathy is perhaps the most common and most severe form of kidney disease. Proteinuria may be a cost-effective screening test in the long-term management of HIV-infected children, however, there are no definite recommendations for the same. Other important renal diseases are HIV immune complex kidney disease, thrombotic microangiopathy, interstitial nephritis and vasculitis.

Vitamin D may play an important role in a range of disease processes. In the general population, lower vitamin D levels have been associated with kidney dysfunction. HIV-infected populations have a higher risk of chronic kidney disease. Few studies have examined the link between lower vitamin D levels and kidney function decline among HIV-infected persons. We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] with kidney function decline in a cohort of HIV-infected white and black men under highly active antiretroviral therapy treatment in the vitamin D ancillary study of the Multicenter AIDS Cohort Study. The associations of 25(OH)D and 1,25(OH) 2 D with annual change in estimated glomerular filtration rate (eGFR) were evaluated using linear mixed effects models. This study included 187 whites and 86 blacks with vitamin D measures and eGFR ≥60 ml/min/1.73 m 2 at baseline. Over a median follow-up of 8.0 years, lower 25(OH)D levels were significantly associated with faster eGFR decline in whites (adjusted annual change in eGFR, tertile 1: -2.06 ml/min/1.73 m 2 vs. tertile 3: -1.23 ml/min/1.73 m 2 , p trend .03), while no significant association was detected in blacks. Lower 1,25(OH) 2 D was associated with faster kidney function decline in both whites and blacks, although the estimates were not statistically significant. In conclusion, lower 25(OH)D levels were significantly associated with faster eGFR decline in a cohort of HIV-infected white men, but not in those with black ancestry. Further research is warranted to investigate the association of 25(OH)D and 1,25(OH) 2 D with kidney function decline in larger and ethnically diverse populations.

The complement system which is a critical mediator of innate immunity plays diverse roles in the neuropathogenesis of HIV-1 infection such as clearing HIV-1 and promoting productive HIV-1 replication. In the development of HIV-1 associated neurological disorders (HAND), there may be an imbalance between complement activation and regulation, which may contribute to the neuronal damage as a consequence of HIV-1 infection. It is well recognized that opiate abuse exacerbates HIV-1 neuropathology, however, little is known about the role of complement proteins in opiate induced neuromodulation, specifically in the presence of co-morbidity such as HIV-1 infection. Complement levels are significantly increased in the HIV-1-infected brain, thus HIV-induced complement synthesis may represent an important mechanism for the pathogenesis of AIDS in the brain, but remains underexplored. Anti-HIV-1 antibodies are able to initiate complement activation in HIV-1 infected CNS cells such as microglia and astrocytes during the course of disease progression; however, this complement activation fails to clear and eradicate HIV-1 from infected cells. In addition, the antiretroviral agents used for HIV therapy cause dysregulation of lipid metabolism, endothelial, and adipocyte cell function, and activation of pro-inflammatory cytokines. We speculate that both HIV-1 and opiates trigger a cytokine-mediated pro-inflammatory stimulus that modulates the complement cascade to exacerbate the virus-induced neurological damage. We examined the expression levels of C1q, SC5b-9, C5L2, C5aR, C3aR, and C9 key members of the complement cascade both in vivo in post mortem brain frontal cortex tissue from patients with HAND who used/did not use heroin, and in vitro using human microglial cultures treated with HIV tat and/or heroin. We observed significant expression of C1q and SC5b-9 by immunofluorescence staining in both the brain cortical and hippocampal region in HAND patients who abused heroin. Additionally, we observed increased gene expression of C5aR, C3aR, and C9 in the brain tissue of both HIV-1 infected patients with HAND who abused and did not abuse heroin, as compared to HIV negative controls. Our results show a significant increase in the expression of complement proteins C9, C5L2, C5aR, and C3aR in HIV transfected microglia and an additional increase in the levels of these complement proteins in heroin-treated HIV transfected microglia. This study highlights the a) potential roles of complement proteins in the pathogenesis of HIV-1-related neurodegenerative disorders; b) the combined effect of an opiate, like heroin, and HIV viral protein like HIV tat on complement proteins in normal human microglial cells and HIV transfected microglial cells. In the context of HAND, targeting selective steps in the complement cascade could help ameliorating the HIV burden in the CNS, thus investigations of complement-related therapeutic approaches for the treatment of HAND are warranted.

The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4 + (cells/mm 3 ) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m 2 , calculated by CKD-EPI equation), over time using longitudinal mixed models. Of 4685 START participants, 4629 (2294 in immediate and 2335 deferred arm) were included. Median baseline CD4 + and eGFR were 651 and 111.5, respectively. ART was initiated in 2271 participants (99.0%) in the immediate and 1127 (48.3%) in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 (95% CI 0.003-1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21-2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84-4.97) versus non-Blacks (1.05, 95% CI 0.33-1.77) (P < 0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55-1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage., (Copyright © 2017 by the American Society of Nephrology.)

Background: FTC/TAF was shown to be noninferior to FTC/TDF with advantages in markers of renal and bone safety., Objective: To evaluate the efficacy and safety of switching to FTC/TAF from FTC/TDF by third agent (boosted protease inhibitor [PI] vs. unboosted third agent)., Methods: We conducted a 48-week subgroup analysis based on third agent from a randomized, double blind study in virologically suppressed adults on a FTC/TDF-containing regimen who switched to FTC/TAF vs. continued FTC/TDF while remaining on the same third agent., Results: We randomized (1:1) 663 participants to either switch to FTC/TAF (N = 333) or continue FTC/TDF (N = 330), each with baseline third agent stratifying by class of third agent in the prior treatment regimen (boosted PI 46%, unboosted third agent 54%). At week 48, significant differences in renal biomarkers and bone mineral density were observed favoring FTC/TAF over FTC/TDF (p < 0.05 for all), with similar improvements in the FTC/TAF arm in those who received boosted PI vs. unboosted third agents. At week 48, virologic success rates were similar between treatment groups for those who received a boosted PI (FTC/TAF 92%, FTC/TDF 93%) and for those who received an unboosted third agent (97% vs. 93%)., Conclusions: In virologically suppressed patients switching to FTC/TAF from FTC/TDF, high rates of virologic suppression were maintained, while renal and bone safety parameters improved, regardless of whether participants were receiving a boosted PI or an unboosted third agent. FTC/TAF offers safety advantages over FTC/TDF and can be an important option as an NRTI backbone given with a variety of third agents.

Renal disease is an important and commonly encountered co-morbidity in HIV infection. Despite this, few data are available concerning renal disease in this patient group. A retrospective review was conducted of all HIV-positive patients of an inner metropolitan sexual health service who attended from 1 August 2013 to 31 July 2014 for HIV management. One hundred eighty-eight HIV-positive patients attended the clinic during the study period. The majority were male (96%), Caucasian (70%) and 30-39 years of age (37%). There was a high prevalence of renal risk factors in the population, including potentially nephrotoxic antiretroviral therapy (61%), smoking (38%), hypertension (12%), dyslipidemia (11%) and hepatitis C co-infection (7%). In the previous year, measurements of estimated glomerular filtration rate were performed in all patients, but measurements of lipid profiles, urinary protein and serum phosphate were performed within the last year in only 48%, 33% and 30% of patients, respectively. These are the first comprehensive data regarding renal disease, associated risk factors and screening and management practices in the HIV-positive patient population of a specialized sexual health service in Australia. This patient population demonstrates a particularly high prevalence of risk factors for renal disease. Despite this, screening investigations were not performed as recommended. This represents a potential area to improve patient care., (© 2017 Asian Pacific Society of Nephrology.)

The introduction in the late 20(th) century of combination antiretroviral therapy (cART) to treat patients infected with HIV has changed the natural history of the disease from an acute illness that rapidly culminates in death, to a chronic condition that can be managed with medications. Over the past decade the epidemiology of kidney disease in US patients infected with HIV has changed, perhaps because of the increased availability and use of cART. Patients with HIV infection exhibit unique immunologic characteristics, including immunodeficiency and dysregulation of immunoglobulin synthetic responses and T-cell function, which can result in glomerular immune complex deposition and subsequent kidney injury. This Review examines the differential diagnoses of HIV-associated immune complex kidney diseases (HIVICD), and discusses the clinical manifestations and mechanisms underlying their development. We address the issues associated with treatment, clinical outcomes, and research needs to enhance our ability to diagnose and optimally treat patients with HIVICD.

The cause of the human immunodeficiency virus (HIV) epidemic in South Africa (SA) was worsened by the denial by key political players that HIV causes acquired immunodeficiency syndrome (AIDS). South Africa continues to have the highest rate of HIV world-wide, which has had a huge impact on the development of both chronic kidney disease and acute kidney injury. Fortunately, there is now an effective antiretroviral therapy (ART) roll-out program. SA is also dealing with a collision of epidemics of HIV, tuberculosis, and non-communicable disease, particularly hypertension and diabetes. This has been evidenced by recent data seen in the reinstated SA renal registry. There is also an unacceptably high rate of tuberculosis in regions of SA, this has led to high rates of granulomatous interstitial nephritis (GIN) and case reports of TB-GIN immune reconstitution inflammatory syndrome (IRIS). HIV-associated nephropathy (HIVAN) remains common in SA and responds well to ART. The definitive diagnosis requires a renal biopsy, which is often not possible in many regions of sub-Saharan Africa. Unfortunately, there is still a high rate of HIVAN in SA due to late presentation and lack of effective screening for renal disease in HIV-positive patients. Transplantation for HIV-positive donors to positive recipients offers a unique and encouraging way forward for these patients.

Objectives: To describe the spectrum of renal tubular disease (RTD) in HIV-positive patients and its association with exposure to antiretroviral therapy (ART)., Design: Review of 265 consecutive renal biopsies from HIV-positive patients attending eight clinics in the United Kingdom between 2000 and 2012., Methods: We described the clinical characteristics of patients with RTD and compared current/recent exposure (at the time of, or up to 3 months prior to the date of biopsy) to potentially nephrotoxic ART [tenofovir (TDF), atazanavir (ATV), indinavir (IDV) and lopinavir/ritonavir (LPV/r)]. We also analysed the incidence of RTD in the UK CHIC cohort. Kruskall-Wallis, analysis of variance and Fisher's exact tests were used to evaluate between-group differences., Results: Of the 60 RTD cases, 54 (90%) were included in the analyses. RTD comprised of three distinct patterns: acute tubular injury (ATI, n = 22), tubulo-interstitial nephritis (TIN, n = 20) and interstitial fibrosis and tubular atrophy (IFTA, n = 12). Compared with TIN and IFTA, ATI cases were less likely to be of black ethnicity (10 vs. 42-55%; P = 0.006), more likely to be on ART (100 vs. 55-68%; P = 0.001), with HIV-RNA below 200 copies/ml (100 vs. 54-58%; P < 0.001), and more likely to have current/recent exposure to TDF (P < 0.001). We did not find evidence for an association between exposure to TDF, ATV/r or LPV/r and either TIN or IFTA., Conclusion: RTD was present in approximately 20% of renal biopsies and comprised three distinct injury patterns with considerable clinical overlap. ATI was associated with TDF exposure, although the overall incidence of biopsy-defined ATI was low.

This paper reviews the current literature and information on the combination drug Complera(™) (rilpivirine/emtricitabine/tenofovir disoproxil fumarate) that was approved by the Food and Drug Administration (FDA) in August 2011. PubMed, Cochrane and Embase (2001-2014) were searched for primary and review articles on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate, individually or in combination. Data from drug manufacturer and product label was also used. Clinical trial reports were selected, extracted and analyzed to include relevant and recent ones. Selected English-language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results from two phase 3 randomized double blind trials (ECHO and THRIVE) showed that rilpivirine is non-inferior to efavirenz in suppressing viral load below 50 copies/mL in anti-retroviral therapy (ART) naïve human immunodeficiency virus (HIV) infected patients. In addition, psychiatric disturbances, rash and increase in lipid levels occurred less frequently with rilpivirine when compared to efavirenz. However, virological failure and drug resistance were higher with rilpivirine in patients with baseline viral load >100,000 copies/mL. Rilpivirine showed cross resistance to efavirenz and etravirine. Efavirenz, on the other hand, did not demonstrate cross resistance to rilpivirine and etravirine, leaving the latter drugs as options for use in case of virological failure with efavirenz. Complera(™) remains an acceptable alternative treatment to Atripla(™) in ART naïve patients who have a pre-ART plasma HIV RNA <100,000 copies/mL and CD4 count >200 cells/mm(3) with non-inferior efficacy and better safety and tolerability., (Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

HIV is a highly adaptive, rapidly evolving virus, which is associated with renal diseases including collapsing glomerulopathy-the classic histomorphological form of HIV-associated nephropathy. Other nephropathies related to viral factors include HIV-immune-complex kidney disease and thrombotic microangiopathy. The distribution of HIV-associated kidney diseases has changed over time and continues to vary across geographic regions worldwide. The reasons for this diversity are complex and include a critical role of APOL1 variants and possibly other genetic factors, disparities in access to effective antiviral therapies, and likely other factors that we do not yet fully understand. The mechanisms responsible for HIVAN, including HIV infection of podocytes and tubular epithelial cells, the molecules responsible for HIV entry, and diverse mechanisms of cell injury, have been the focus of much study. Although combined antiretroviral therapy is effective at preventing and reversing HIVAN, focal segmental glomerulosclerosis, arterionephrosclerosis and diabetic nephropathy are increasingly common in individuals who have received such therapy for many years. These diseases are associated with metabolic syndrome, obesity and premature ageing. Future directions for HIV-related kidney disease will involve regular screening for drug nephrotoxicity and incipient renal disease, as well as further research into the mechanisms by which chronic inflammation can lead to glomerular disease.

Background: Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women., Study Design: Retrospective cohort analysis., Setting & Participants: Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years., Predictor: The primary predictor was serum albumin concentration., Outcomes: We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR)., Measurements: Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression., Results: After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001)., Limitations: The cohort is composed of only female participants from urban communities within the United States., Conclusions: Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria., (Published by Elsevier Inc.)

Background: In HIV-infected adults, elevated albumin has been associated with increased inflammatory activity, HIV-related nephropathy, and type 2 diabetes. Data on albuminuria in HIV-infected children are very scarce, and guidelines do not include routine determination of urinary albumin/creatinine ratio in this population., Methods: We performed a cross-sectional study in a cohort of HIV-infected pediatric patients. Urinary protein/creatinine and albumin/creatinine ratios and hematuria were determined from at least three morning urine samples, and glomerular filtration rate (GFR) was estimated from creatinine levels. Persistent renal damage was defined according to the presence of at least two sequentially abnormal values in one of the parameters. The relationship between renal damage, HIV-related variables, and metabolic comorbidities (dyslipidemia, fat redistribution, glucose intolerance, hypertension) was investigated., Results: Symptom-free renal damage was observed in 13 of 68 patients (19.1%) and mainly consisted of persistent proteinuria (17.6%); glomerular proteinuria was twice as prevalent as tubular proteinuria. GFR were normal in all cases. No relationship between renal markers and HIV-related variables or metabolic comorbidities was observed., Conclusions: Mild proteinuria affected approximately one fifth of patients in our cohort. The determination of albuminuria allowed the differentiation between glomerular and tubular proteinuria, although no relationship with metabolic comorbidities was observed.

Asia is seeing a rise in noncommunicable diseases in their general population and among people living with HIV. Many Asians have low body weight, which can lead to higher plasma concentrations of antiretrovirals and, as a result, their toxicities. Examples are metabolic complications from protease inhibitors, chronic kidney disease from tenofovir, and hepatotoxicity from nevirapine. Asia has not only the highest burden of hepatitis B viral infection than any other continent but also a predominance of genotypes B and C, the latter associated with higher risk for hepatocellular carcinoma. HIV-associated neurocognitive disorders are equally common among Asians as other populations. Diastolic dysfunction and asymptomatic myocardial ischemia are not infrequent. Non-Hodgkin lymphoma is the most common AIDS-related cancer, whereas Kaposi sarcoma is relatively infrequent. Emerging data show high prevalence of human papillomavirus-associated anal dysplasia in men who have sex with men. Resource-limited countries in Asia suffer from lack of resources for national screening programs of noncommunicable diseases, which, in turn, limits the epidemiologic data that exist to guide the use of national health resources.

Despite effective antiretroviral therapy (ART), HIV-infected individuals have residual chronic immune activation that contributes to the pathogenesis of HIV infection. This immune system dysregulation is a pathogenic state manifested by very low naïve T-cell numbers and increased terminally differentiated effector cells that generate excessive proinflammatory cytokines with limited functionality. Immune exhaustion leaves an individual at risk for accelerated aging-related diseases, including renal dysfunction, atherosclerosis, diabetes mellitus, and osteoporosis. We highlight research that clarifies the role of HIV, ART, and other factors that contribute to the development of these diseases among HIV-infected persons., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The epidemiology of kidney disease in HIV-infected individuals has changed significantly since the introduction of combination antiretroviral therapy (cART) in the mid 1990s. HIV-associated nephropathy (HIVAN), an aggressive form of collapsing focal segmental glomerulosclerosis (FSGS) caused by direct HIV infection of the kidney in a genetically susceptible host, emerged early in the HIV epidemic as a leading cause of end-stage renal disease. With the widespread use of cART, HIVAN is increasingly rare in populations with access to care, and the spectrum of HIV-related chronic kidney disease now reflects the growing burden of comorbid disease in the aging HIV population. Nonetheless, available data suggest that both HIV infection and cART nephrotoxicity continue to contribute to the increased risk of chronic kidney disease in HIV-infected individuals in the United States and Europe. Despite the genetic susceptibility to HIVAN in individuals of West African descent, limited data are available to define the prevalence and spectrum of HIV-related kidney disease in sub-Saharan Africa, which is home to two-thirds of the world's HIV population. In this mini-review, we characterize the changing epidemiology of HIV-related chronic kidney disease in Western nations and in sub-Saharan Africa.

Background: In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline elaborated the identification and prognosis of CKD by combining albuminuria with estimated glomerular filtration rate (eGFR). Identification of CKD with a high risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)-infected individuals by applying the new guideline., Methods: A total of 1,447 HIV-infected patients (1,351 male, 96 female; mean age 44.4 ± 11.5 years) were classified using a combination of eGFR and dipstick proteinuria, as a convenient alternative to albuminuria. Proteinuria was classified into 3 grades-(A1) - and +/- , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades-(G1) ≤90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 mL/min/1.73 m(2)., Results: Mean CD4 cell count was 487 ± 214 /μL, with 80.7 % of patients having an undetectable HIV-RNA level. The prevalence of CKD stage ≤2 and stage ≥3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using the new KDIGO classification, the prevalence of CKD with either a low (green) or moderately increased (yellow) risk was 96.9 %, while the prevalence for a high (orange) and very high (red) risk was 3.1 %., Conclusion: The use of the new KDIGO classification may reduce the prevalence of HIV-infected CKD individuals who are at high risk for a poor prognosis by nearly a half.

Purpose of Review: To review unique considerations in the epidemiology, diagnosis, and management of kidney disease in older adults with HIV., Recent Findings: HIV infection may accelerate the course of kidney disease associated with traditional risk factors, such as diabetes, which are more common in older adults. The risks of acute and chronic kidney disease are increased both with HIV infection and with older age. Although the prevalence of chronic kidney disease is higher among HIV-infected adults than among HIV-negative adults, the mean age at diagnosis of end-stage renal disease is similar. Recent studies have supported the use of newer creatinine-based kidney function estimates in HIV-infected adults, although data in older adults are limited. These estimates are susceptible to artifact in the setting of newer medications that interfere with the secretion of creatinine, including cobicistat and dolutegravir. The management of kidney disease in older adults with HIV infection may be complicated by polypharmacy and increased risk for medication toxicity., Summary: With aging of the HIV-infected population, age-related comorbid conditions such as kidney disease are increasingly important causes of morbidity and mortality. Although recent data do not support premature aging of HIV-infected individuals with respect to kidney disease, the risk of acute and chronic kidney disease is increased by HIV infection and its treatment.

Background: Pain, sleep, and functional disturbances are a common occurrence in people living with HIV/AIDS-related distal sensory peripheral neuropathy (PLWHA-DSPN) yet lack group classification and quantification., Methods: A total of 46 PLWHA-DSPN were recruited, as part of a 2-group intervention study, to complete the Neuropathic Pain Scale and the Pittsburgh Sleep Quality Index (PSQI) questionnaires. The participant's performance during a forward reach task and walking distance in 6 minutes was recorded as a measure of function., Results: The pain (60.77 +/- 17.85) and sleep (14.62 +/- 4.28) scores denote marked pain and sleep disturbances, compared to seronegative, age-matched individuals. The ambulation distance was limited (243.99 +/- 141.04 m) and inversely associated with the PSQI-sleep efficiency subscale (rs = -.35, P < .05). The average reaching distances measured (36.07 +/- 7.37 cm) were similar to seronegative, age-matched individuals. Pain, sleep, and functional measures exhibited significant associations., Conclusions: The data collected suggest that PLWHA-DSPN report moderate-to-severe pain and significant sleep disturbances and exhibit limited ambulation distances.

Objectives: To determine the relationship between measures of renal function [current estimated glomerular filtration rate (eGFR) and proportion of follow-up with a low eGFR (%FU ≤60 ml/min)] and fatal/ nonfatal AIDS, non-AIDS events and all-cause mortality., Design: An observational, longitudinal cohort study of 12 155 persons from EuroSIDA., Methods: Persons with at least one eGFR measurement after 1 January 2004, using the CKD-EPI formula, were included. Poisson regression analyses were used to determine whether current eGFR or %FU of 60 ml/min or less were independent prognostic markers for clinical events., Results: During 61 425 person-years of follow-up (PYFU), the crude incidence of deaths was 11.1/1000 PYFU [95% confidence interval (CI) 10.0-12.1] at current eGFR more than 90 ml/min and 199.6 (95% CI 1144.3-254.3/1000 PYFU) when current eGFR was 30 ml/min or less. Corresponding figures for AIDS were 12.2 (11.1-13.3) and 63.9 (36.5-103.7) and for non-AIDS were 16.0 (14.8-17.3) and 203.6 (147.7-259.5). After adjustment, current eGFR of 30 ml/min or less was a strong predictor of death [adjusted incidence rate ratios (aIRR) 4.35; 95% CI 3.20-5.91] and non-AIDS events (3.63; 95% CI 2.57-5.13), although the relationship with AIDS was less strong (1.45; 95% CI 1.01-2.08). After adjustment, %FU of 60 ml/min or less was associated with a 22% increased incidence of death (aIRR 1.22 per 10% longer; 95% CI 1.18-1.27), a 13% increased incidence of non-AIDS events (95% CI 1.08-1.18) and a 15% increased incidence of AIDS events (95% CI 1.06-1.24)., Conclusion: Both current eGFR and %FU of 60 ml/min or less were associated with death and non-AIDS events in HIV-positive persons. Our findings highlight the association between underlying renal dysfunction and morbidity and mortality in HIV infection, although reverse causality cannot be excluded.

Objectives: Because there is only one study to our knowledge on the prevalence of restless legs syndrome (RLS) in sub-Saharan Africa and RLS is more common in patients with some pain syndromes, we aimed to determine the prevalence of RLS in a population with chronic pain in Maputo, Mozambique., Methods: Our study was conducted in the Pain Unit of the Central Hospital of Maputo, Mozambique. Patients were individually interviewed by a neurologist, and only those fulfilling the criteria were included. After collection of demographic data and pain features, the patients answered the screening questions regarding RLS., Results: A total of 123 patients with pain were interviewed. Five individuals were excluded. RLS was found in eight (6.77%) of 118 patients. The mean age of the eight patients with RLS was 54.6years. Five patients (62.5%) were women and six (75%) were black individuals. Seven (87.5%) patients were diagnosed with neuropathic pain; one of them had AIDS and another one (12.5%) had orthopedic pain. The presence of hypertension and neuropathies was more frequent in the RLS group., Conclusion: Despite the secondary causes involved, we believe that it is relevant to report the RLS prevalence detected in our study., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Objective: Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART)., Patients and Methods: Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period)., Results: 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease., Conclusion: The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population., (© Georg Thieme Verlag KG Stuttgart · New York.)

Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5-29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.