Dysfunction In HIV-infected Patients Research Articles

Renal dysfunction in HIV-infected patients commencing antiretroviral therapy in a treatment centre in southern Nigeria

Objective: As HIV becomes a more manageable chronic condition, with increasing life expectancy and an ageing population, kidney disease due to HIV or antiretroviral therapy (ART) have become more prominent. Moreover, the nephrotoxic potential of some frontline antiretroviral drugs has become established. The study aimed to evaluate the prevalence and risk factors for renal dysfunction among HIV-infected patients commencing ART at a southern Nigerian tertiary hospital. Methods: A cross-sectional prospective study involving 263 HIV-infected treatment-naïve patients commencing ART at the University of Port Harcourt Teaching Hospital, Port Harcourt. Blood and urine samples were taken from randomly recruited patients for appropriate laboratory analysis. The MDRD formulae were used for evaluating renal function while renal dysfunction was defined as an estimated glomerular filtration rate ≤ 60mls/min/1.73m2 and /or proteinuria. Results: The average age of enrolled patients was 36.3±10.15 with 59.3% women. 33.8% had proteinuria and 6.5% had eGFR<60mls/min/1.73m2. The prevalence of renal dysfunction was 37.6%. Age > 50 years, anaemia and use of Traditional medicine were independent predictors of renal dysfunction. Conclusion: In this cohort of treatment naïve HIV patients, a high prevalence of renal dysfunction exists. Older age, anaemia and traditional medicine use were predictors of renal dysfunction. There is a need for clinicians to monitor these variables, especially the use of Traditional medicine which is easily overlooked in practice.

Myocardial ischemia and left ventricular diastolic dysfunction in HIV infected patients and asymptomatic for coronary artery disease

Highly active antiretroviral therapy (HAART) allows chronicity of AIDS evolution, leading to association of other pathologies such as coronary artery disease (CAD). Myocardial ischemia (MI) and left ventricular diastolic dysfunction (LVDD) evaluation in HIV-infected patients may favor primary prevention of CAD. The study aimed to evaluate frequencies of MI and LVDD in the population living with the human immunodeficiency virus (PLHIV) and asymptomatic for CAD. We analyzed data from 110 HIV-infected patients who underwent clinical and laboratory evaluation, treadmill exercise stress test, and transthoracic echocardiogram, and compared it with 2,619 healthy individuals from the control group (non-HIV and non-CAD), selected from the database. HIV-infected patients presented lower average age (51.5 ± 7.7), systemic arterial hypertension (28.0%) and dyslipidemia frequencies (32.0%). On the other hand, their MI frequency was twice as high (14.7%); and diastolic dysfunction (DD) percentage was higher in ischemic patients (45.5%). In the HIV-infected group, MI frequency was 10.0%, while that of DD was 18.2%. MI was twice as frequent among HIV infected patients compared to uninfected, despite lower frequency of risk factors for CAD. Non-ischemic patients living with HIV had a frequency of DD more than twice compared to the control individuals.

Near-infrared spectroscopy-derived muscle oxygen saturation during exercise recovery and flow-mediated dilation are impaired in HIV-infected patients

Highly active antiretroviral therapy has been associated with the presence of endothelial dysfunction in HIV-infected patients, which may impair oxygen delivery to muscles during exercise and exercise recovery. Near-infrared spectroscopy (NIRS) has been used to assess muscle oxygen saturation (SmO2) kinetics during exercise in different clinical populations in order to evaluate the balance between oxygen delivery and utilization by muscles. However, studies assessing SmO2 in HIV-infected patients have not been conducted. Therefore, the aim of the study was to evaluate NIRS-derived SmO2 during rhythmic handgrip exercise and flow-mediated dilation (FMD) in HIV-infected patients (HIV) compared to non-HIV-infected controls (N-HIV). Eighteen HIV and 17 N-HIV individuals underwent FMD assessment by ultrasound. The subjects then performed one set of rhythmic handgrip exercise until fatigue at 30% maximal isometric voluntary contraction. SmO2 was measured during entire exercise and 2-min exercise 3recovery. Muscle oxygen resaturation rate (upslope of the SmO2 over 10 s of recovery) was calculated. A significant lower FMD (3.5 ± 1.7 vs 5.9 ± 1.5%, P < 0.001) and slower oxygen resaturation rate (0.78 ± 0.4 vs 1.14 ± 0.4%·s−1, P = 0.020) in HIV as compared to N-HIV group were observed. In conclusion, our findings demonstrated that HIV-infected patients had reduced FMD and impaired muscle oxygenation during exercise recovery compared to non-HIV individuals.

Evaluation of Relationship between fQRS and CD4/CD8 Ratio in Patients with HIV.

Objectives:Myocardial dysfunction is an important cause of morbidity in human immunodeficiency virus (HIV)-infected patients. Decline in CD4 T-cell level and reversal of CD4/CD8 ratio was associated with cardiovascular events. Fragmented QRS (fQRS) can show myocardial dysfunction and cardiovascular events. The aim of this study is to investigate the presence of fQRS in HIV-infected patients and the factors affecting it.Methods:This case-control study included 153 outpatient HIV patients (97% male) and 141 healthy subjects (96% male). Patients with cardiac disease history, arrhythmia, diabetes, cancer disease, and thyroid dysfunction were excluded from the study. Electrocardiogram, echocardiography, and biochemistry tests were performed to all participants. CD4 and CD8 T cell count, and HIV RNA level were measured in HIV-infected patients.Results:Both groups had similar basal characteristics. Mean CD4 T-cell level was 356 cell/cm3, HIV was under control in 48%, and the rate of antiretroviral treatment use was 64%. HIV-infected patients had lower left ventricular ejection fraction (LVEF), higher Tei index, and more fQRS. HIV-infected patients with fQRS had lower nadir CD4 T-cell levels, lower CD4/CD8 ratio, and higher Tie index. In multivariate analysis, CD4/CD8 ratio and LVEF were found to be independent predictors of fQRS in HIV-infected patients.Conclusion:Myocardial dysfunction can be seen in HIV-infected patients. Caution should be exercised in terms of myocardial dysfunction in HIV-infected patients with low CD4/CD8 ratio.

Nephrotoxicity of Antimicrobials and Antibiotics.

Medication-induced nephrotoxicity remains one of the most common causes of acute kidney injury (AKI) among hospitalized patients. Within the extensive group of medications associated with AKI, antibiotics and other antimicrobials are well recognized triggers of structural and functional renal impairment. Clinical manifestations range from mild forms of tubular injury to significant deterioration of kidney function requiring acute renal replacement therapy. Several mechanisms are described, although the most frequent are acute interstitial nephritis, acute tubular necrosis, intratubular crystal deposition, and proximal/distal tubulopathy with electrolyte wasting abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease, and concomitant use of medication with nephrotoxic potential. Prevention and early recognition of AKI represent the standard approach to mitigate AKI and avoid morbidity.

Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients.

Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr). The majority of patients received TDF. Abnormal uRBP/Cr was more frequent in TDF recipients: eGFR <90 mL/min and TDF were predictors in the whole cohort, whereas eGFR <90 mL/min, TDF concentrations and CYP24A1-3999TT in TDF-treated patients. Phosphate levels were higher low VD level patients: age <50 years, CYP27B1 + 2838CC genotype and non-European ancestry were predictors. PTH levels were border-line higher in TDF patients: non-European ancestry, females, TDF, VD levels < 30 ng/mL and SLC28A2-124CT/TT and ABCC2-24CC were predictors. For the first time, SNPs were associated with PTH, phosphate, calcium and tubular dysfunction in HIV-infected patients.

Prevalence and risk factors for erectile dysfunction in HIV-infected patients in Salvador, Brazil

BackgroundEffective antiretroviral therapy (ART) has increased life expectancy for HIV patients to levels close to that observed for general population. Comorbidities are also increasing, due to ageing of such population. Erectile dysfunction (ED) has been a frequent finding in men living with HIV. ObjectivesThe goals of the present study were to define the prevalence of ED and associated factors in HIV-infected men, in a referral center of Salvador city, Brazil. MethodsHIV-infected men ≥18 years of age, receiving care at the AIDS Clinics of Complexo Hospitalar Professor Edgard Santos (C-HUPES), Universidade Federal da Bahia were consecutively included in the study until the estimated sample size (N=134) was reached. Patients filled a structured questionnaire on clinical-epidemiological characteristics, as well as the International Index on Erectile Function to assess ED. ResultsMost (55%) were black and single (79%), mean age 44.8 years. ED was detected in 29 (21.6%) patients; 86% of ED cases were classified as severe. The only factors associated with ED were low income (p=0.02) and unemployment (p=0.01). No association was found between ED and frequency of comorbidities, age, or ART used by patients. ConclusionIn a referral center in Salvador city, socio-economic problems were the main factors associated with ED. Psychological impact of poor social conditions should be routinely assessed in patients with ED to implement preventive measures for ED.

The Use of Two-Dimensional Strain Measured by Speckle Tracking in the Identification of Incipient Ventricular Dysfunction in HIV-Infected Patients on Antiretroviral Therapy, Untreated HIV Patients and Healthy Controls.

BackgroundMost cardiovascular abnormalities in patients infected with the human immunodeficiency virus (HIV) have been associated with myocardial damage directly caused by the virus. Some cases, however, may be associated with adverse effects from antiretroviral therapy (ART). New ventricular function assessment techniques are capable of detecting early changes in the cardiac function of HIV-infected patients using or not using ART. The usefulness of these techniques has been little employed in these patients.ObjectivesTo investigate the potential influence of antiretroviral therapy (ART) on the occurrence of subclinical left ventricular systolic dysfunction evaluated by myocardial strain rate analysis using two-dimensional speckle tracking echocardiography (2-D Echo) in treated HIV patients compared to untreated patients and healthy individuals.MethodsSixty-eight HIV-infected patients with no cardiovascular symptoms, normal left ventricular (LV) ejection fraction (> 0.55 on 2-D Echo) were divided into three groups: 11 patients not using antiretroviral therapy (NT), 24 using protease inhibitor (PI) and 33 using non-nucleoside reverse transcriptase inhibitor (NNRTI). We also studied 30 normal non-HIV infected individuals (Ctrl). Demographic, clinical, biochemical and anthropometric data were collected. Preliminary transthoracic echocardiography included study of myocardial strain using two-dimensional speckle tracking. We studied strain and strain rate in the seventeen left ventricular (LV) myocardial segments in the longitudinal, circumferential and radial axes. Statistical analysis of the data was done with IBM SPSS - version 20 for Windows. Upon analysis of the data, namely the normality of independent variables in the different groups and the homogeneity of the variances between the groups, Kruskal-Wallis’ non-parametric test was done, followed by Dunn’s multiple comparison tests to test the significance of the differences between the values measured in the study groups. A significance level of 5% was adopted for decision-making on statistical tests.ResultsThe mean age of HIV patients was 40 ± 8.65 years and the mean age of controls was 50 ± 11.6 years (p < 0.001). Median LV global longitudinal strain (GLS) of NT patients (-17.70%), PI patients (-18.27%) and NNRTIs (-18.47%) were significantly lower than that of the Ctrl group (-20.77%; p = 0.001). There was no significant difference in mean SLG between treated patients (PI, NNRTI) and untreated (NT) patients. No significant differences were observed in mean circumferential and radial strain, nor on circumferential and radial strain rates between the NT, PI, NNRTI and Ctrl groups.ConclusionThe data suggest that HIV patients present, on myocardial strain measured by speckle tracking, signs of early LV systolic dysfunction that seem to be unrelated to the presence of ART. The prognostic significance of this condition in these patients deserves further studies.

Pattern of Thyroid Dysfunction in HIV Patients

Introduction: Abnormalities of the endocrine glands functions are not uncommon in patients infected with HIV. Many studies have shown high prevalence of thyroid dysfunction in HIV patients. We have undertaken this study to know pattern of thyroid dysfunction in patients registered to our ART centre. Materials and methods: 100 HIV patients registered in ARTcentre of government medical college Jammu were enrolled for study. Besides baseline investigation FT3, FT4, TSH levels and CD4 counts were assessed in all patients. Results: 64% were women and 36% were men and mean age of our study group patients was 37.19±8.79. Out of 100 seropositive HIV patients, 69% were on antiretroviral therapy. Sick euthyroid syndrome was observed in 13% patients, subclinical hypothyroidism in 9% and 78% were euthyroid. Point prevalence of thyroid dysfunction in HIV infected patients was observed to be 22%. Conclusion: Thyroid dysfunction is very common in patients infected with HIV and should be assessed in all patients, as thyroid hormones play important role not only in metabolism but also in uence immune system.

Abstract 513: Lower Nadir Cd4 T-cell Count is a Strong Predictor of Endothelial Dysfunction in HIV Infected Patients

Background: Nadir CD4 T-cell count is a predictor of negative outcomes in HIV -infected patients and strongly correlates with WHO disease staging. There is lack of data pertaining the relationship between vascular function and nadir CD4 in patients without risk factors of hypertension and diabetes. Therefore we investigated the association between low nadir CD4 T-cells and endothelial function in these otherwise cardiovascular healthy patients. Methods: We conducted a study of 19 HIV-infected men on antiretroviral therapy with undetectable plasma RNA levels without hypertension or diabetes. Vascular reactivity index (VRI), a marker for vascular endothelial function, was measured via VENDYS technique using temperature rebound in response to hyperemic blood flow and vasodilation to the forearm following a 5-minute cuff occlusion of the brachial artery. Results: VRI showed a significant correlation with low nadir CD4 count (p = 0.019) (Figure 1). Lower CD4 counts were associated with significant endothelial dysfunction. We examined the effect of potential mediators on such association. No significant correlation was found with LDL-C (p=0.60), HDL-C (p=0.59), systolic and diastolic blood pressures (p=0.12 and 0.13) or history of smoking (p=0.55) with VRI in the studied HIV cohort. Conclusion: Low nadir CD4 count remained independently associated with vascular reactivity index and thus a significant clinical predictor of endothelial dysfunction in HIV infected patients with no history of hypertension or diabetes even before clinical evidence of cardiovascular disease. Vascular Reactivity Index vs CD4 Nadir(Figure1).

Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable.

HIV-associated neurocognitive disorders (HAND) remain prevalent in the combined antiretroviral therapy (CART) era, especially the milder forms. Despite these milder phenotypes, we have shown that motor abnormalities persist and have quantified them with the HIV Dementia Motor Scale (HDMS). Our objectives were to replicate, in an independent sample, our prior findings that the HDMS is associated with cognitive impairment in HIV, while adding consideration of age-associated comorbidities such as cerebrovascular disease, and to examine the longitudinal trajectories of cognitive and motor dysfunction. We included all participants enrolled in the Manhattan HIV Brain Bank (MHBB) from January 2007 to May 2017 who had complete baseline data (N = 164). MHBB participants undergo standardized longitudinal assessments including documentation of comorbidities and medications, blood work, the HDMS, and neurocognitive testing. We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact.

Methamphetamine increases HIV infectivity in neural progenitor cells

HIV-1 infection and methamphetamine (METH) abuse frequently occur simultaneously and may have synergistic pathological effects. Although HIV-positive/active METH users have been shown to have higher HIV viral loads and experience more severe neurological complications than non-users, the direct impact of METH on HIV infection and its link to the development of neurocognitive alternations are still poorly understood. In the present study, we hypothesized that METH impacts HIV infection of neural progenitor cells (NPCs) by a mechanism encompassing NFκB/SP1-mediated HIV LTR activation. Mouse and human NPCs were infected with EcoHIV (modified HIV virus infectious to mice) and HIV, respectively, in the presence or absence of METH (50 or 100 μm). Pretreatment with METH, but not simultaneous exposure, significantly increased HIV production in both mouse and human NPCs. To determine the mechanisms underlying these effects, cells were transfected with different variants of HIV LTR promoters and then exposed to METH. METH treatment induced transcriptional activity of the HIV LTR promotor, an effect that required both NFκB and SP1 signaling. Pretreatment with METH also decreased neuronal differentiation of HIV-infected NPCs in both in vitro and in vivo settings. Importantly, NPC-derived daughter cells appeared to be latently infected with HIV. This study indicates that METH increases HIV infectivity of NPCs, through the NFκB/SP1-dependent activation of the HIV LTR and with the subsequent alterations of NPC neurogenesis. Such events may underlie METH- exacerbated neurocognitive dysfunction in HIV-infected patients.

Mucosal Regulatory T Cells and T Helper 17 Cells in HIV-Associated Immune Activation.

Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues. Immune-based therapies are pursued with the goal of improving CD4+ T-cell restoration, as well as reducing chronic immune activation in cART-treated patients. However, the majority of research on immune activation has been derived from analysis of circulating T cells. How immune cell alterations in mucosal tissues contribute to HIV immune dysregulation and the associated risk of non-infectious chronic complications is less studied. Given the significant differences between mucosal T cells and circulating T cells, and the immediate interactions of mucosal T cells with the microbiome, more attention should be devoted to mucosal immune cells and their contribution to systemic immune activation in HIV-infected individuals. Here, we will focus on mucosal immune cells with a specific emphasis on CD4+ T lymphocytes, such as T helper 17 cells and CD4+Foxp3+ regulatory T cells (Tregs), which play crucial roles in maintaining mucosal barrier integrity and preventing inflammation, respectively. We hypothesize that pro-inflammatory milieu in cART-treated patients with immune activation significantly contributes to enhanced loss of Th17 cells and increased frequency of dysregulated Tregs in the mucosa, which in turn may exacerbate immune dysfunction in HIV-infected patients. We also present initial evidence to support this hypothesis. A better comprehension of how pro-inflammatory milieu impacts these two types of cells in the mucosa will shed light on mucosal immune dysfunction and HIV reservoirs, and lead to novel ways to restore immune functions in HIV+ patients.

A study of thyroid dysfunction in HIV infected patients in a tertiary care hospital

Background: Increasing prevalence of thyroid dysfunction has been reported in HIV-infected patients. However, there is insufficient evidence to recommend routine thyroid screening of asymptomatic individuals. Hence, this study was undertaken in an attempt to resolve these issues. Methods: A cross sectional prevalence study was conducted on 75 adult HIV positive patients who did not suffer from hypertension, diabetes, coronary artery disease or thyroid disorder. A detailed history taking and examination was done and biochemical, microbiological and radiological tests were performed in order to reach a diagnosis. In addition, FT3, FT4, TSH and CD4 were done in all the patients. Results: Overt hypothyroidism was found in 2 (3%), subclinical hypothyroidism in 10 (13%), isolated low FT4 in 2 (3%) and sick euthyroidism in 19 (25%) patients. As the stage of HIV advanced, the FT3 and FT4 levels went on decreasing. The TSH levels however, did not correlate with the stage of infection. A direct correlation was found between FT3 and CD4 counts and an inverse correlation between TSH levels and CD4 counts. The mean TSH levels in patients on HAART were significantly higher than in patients not on HAART. Cryptococcal meningitis was found to be associated with subclinical hypothyroidism, CNS toxoplasmosis with isolated low FT4 levels and tuberculosis with sick euthyroidism. Conclusions: Thyroid dysfunction in HIV infected patients was largely asymptomatic. There was a direct correlation between WHO clinical stage of infection and serum FT3 and FT4 levels. TSH levels increased as CD4 counts decreased. Patients on HAART had a high prevalence of subclinical hypothyroidism. No association could be implied between opportunistic infections (OIs) and thyroid dysfunction, due to a small sample size.

Early Diagnosis of Renal Tubular Dysfunction in HIV-Infected Patients; a Case of Interleukin (IL)-18 and other Common Indicators of Renal Toxicity

Background: At present renal dysfunction in clinical practice is measured using serum creatinine values to calculate eGFR (estimated glomerular filtration rate) but creatinine is a late marker of renal dysfunction and is only raised when up to 30-50% of renal function is lost. Methods: Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18. Urinary IL-18 together with other common indicators of renal damage was assessed in 325 HIV patients; of which 66 developed renal dysfunction after 12 weeks of follow-up. Result: Marked increase in IL-18 (p=0.000) was observed at an earlier stage in the renal disease group compared to a delayed elevation of eGFR, serum creatinine, fractional excretion of phosphate and fractional excretion of uric acid which was evident only after 4 weeks. Conclusion: This finding seems to suggest that IL-18 can be used as an early marker of subclinical renal tubular dysfunction in HIV-infected patients, owing to the fact that IL-18 increases in urine only under conditions of marked tubular damage, apoptotic tubular cell shedding, and cell necrosis, associated with deterioration of renal function.

Prevalence and Influencing Factors of Thyroid Dysfunction in HIV-Infected Patients.

Thyroid dysfunction is more common in human immunodeficiency virus (HIV) patients. But the effects of highly active antiretroviral therapy (HAART) and hepatitis B/C virus (HBV/HCV) coinfection on thyroid function is unclear. We retrospectively reviewed the data of 178 HIV patients and determined the prevalence of thyroid dysfunction and the relationship between thyroid hormone levels, CD4 cell count, HIV-1 duration, HAART duration/regimens, and HBV/HCV coinfection. Of the 178 patients, 59 (33.1%) had thyroid dysfunction, mostly hypothyroidism. Thyroid dysfunction was significantly more frequent in the HAART group (41/104, 39.4%) than in the HAART-naïve group (18/74, 24.3%; P < 0.05). The mean CD4 cell count was significantly lower in patients with hypothyroidism (372 ± 331/μL) than in the other patients (P < 0.05). The FT4 level was significantly lower in the HAART group than in the HAART-naïve group (1.09 ± 0.23 versus 1.20 ± 0.29 pg/mL, P < 0.05). FT3/FT4 levels were negatively related to HIV duration and FT3 levels were positively related to CD4 cell (P < 0.05). HBV patients had lower FT3 levels, while HCV patients had higher FT3 and FT4 levels (P < 0.05). Thyroid dysfunction is more common in HIV patients on HAART, mainly manifested as hypothyroidism. FT3/FT4 levels are correlated with HIV progression. HBV/HCV coinfection increases the probability of thyroid dysfunction.

Evaluation of endothelial function and arterial stiffness in HIV-infected patients: a pilot study.

In the era of combination antiretroviral therapy (cART), life expectancy of HIV-infected patients is the same as that of the general population, resulting in increasing prevalence of cardiovascular disease in this patient group. To assess the prevalence of endothelial dysfunction in HIV-infected patients and to identify factors which affect endothelial function and arterial stiffness. Thirty-seven adult HIV-infected patients, regardless of the fact and the type of cART, were enrolled into the study. In patient, reactive hyperaemia peripheral arterial tonometry assessment was performed using the Endo-PAT2000 device (ITAMAR®). This method allows evaluation of endothelial function ant arterial stiffness. Final analysis included 37 patients (median age 38 years, range 32-45 years), including 89.2% men. Endothelial dysfunction was found in 13 (35.1%) HIV-infected patients. We found no differences in demographic and clinical characteristics, laboratory data, and cardiovascular drug therapy between patients with or without endothelial dysfunction, except for platelet count which was higher in patients with endothelial dysfunction (174 [119-193] × 10³/mm3 vs. 222 [168-266] × 10³/mm³, p = 0.03). No demographic or clinical variables were identified as predictors of endothelial dysfunction in HIV-infected patients. In addition, no association was found between factors related to HIV infection, chronic drug therapy and the risk of endothelial dysfunction. Statistically significant correlations were found between arterial stiffness and age (rs = 0.53, p < 0.001), red blood cell count (rs = -0.39, p = 0.018), and platelet count (rs = 0.42, p = 0.009). CD4+ and CD8+ lymphocyte count and viral load were similar in patients with or without endothelial dysfunction. Arterial stiffness was significantly higher in patients with higher viral load (rs = -0.39, p = 0.0018) and in those with established AIDS (9.5 [1.0-16.0] vs. -5 [-10-5], p = 0.009). cART had no effect on endothelial dysfunction, while arterial stiffness was higher in patients treated with cART (10 [0-15] vs. -5 [-10-3], p = 0.014). Endothelial dysfunction is common in HIV-infected patients. In general, none of the analysed factors had an effect on endothelial function but cART had a negative effect on arterial stiffness.

Urinary Interleukin (Il)-18 as an Early Predictive Biomarker of Subclinical Proximal Tubular Dysfunction in HIV-Infected Patients Exposed to Tenofovir

Proximal tubular dysfunction (PTD) is a frequent complication of HIV-infected patients and lack of early biomarkers for PTD has impaired our ability to intervene in a timely manner. In this present study, we tested if interleukin- 18 (IL-18) is a predictive biomarker for PTD in HIV-infected patients on tenofovir (TDF) and Non-tenofovir (N-TDF) antiretroviral therapy and taking as control HIV treatment naive patients. Exclusion criteria included pre-existing renal insufficiency and nephrotoxin used. Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18 in 254 HIV- infected patients at three different points (at baseline, at 4 weeks and at 12 weeks of fellow-up). Using eGFR values, marked decreased in kidney function was detected only at 12 weeks in the TDF regimen group (p=0.003) as compared to other study groups. In contrast, urine IL-18 increased at a much early time (at 4 weeks) particularly in the TDF regimen group (p=0.000) follow by the naive group (p=0.02) and continued to increase up to 12 weeks of follow up. This marked elevation is believed to be progressive. Our results indicate that IL-18 is an early, predictive biomarker of PTD and that this biomarker may allow for the reliable early diagnosis of PTD at all times in HIV-infected patients on TDF at risk of proximal tubular dysfunction, much before the rise in serum creatinine

Strong correlation between protein reagent strip and protein-to-creatinine ratio for detection of renal dysfunction in HIV-infected patients: a cross-sectional study.

BackgroundTubular dysfunction is common in HIV-infected people and detection of proteinuria is essential to identify this problem. In low-income countries, resources for detection of proteinuria using the Kidney Disease Improve Global Outcomes (KDIGO) gold standard urinary protein/creatinine ratio (uPCR) is rarely possible, and use of the protein reagent strip (PRS) could be an option in these places. The aims of this study were to establish the concordance between PRS and uPCR to detect tubular proteinuria in HIV-infected people, and to assess the sensitivity and specificity of PRS as a diagnostic method in this group.MethodsA cross-sectional study was conducted to evaluate the correlation between the two techniques to detect protein in urine. Participants were enrolled for a period of 6 months. The measurements were performed in participants who were on highly active antiretroviral therapy (HAART) or prior to the start of treatment. Proteinuria was defined as uPCR ≥ 150 mg/g, and/or ≥ trace on PRS. A phi coefficient was calculated to establish the degree of correlation. We assessed the sensitivity and specificity of PRS compared with uPCR using standard methods.ResultsA total of 799 subjects were included. Of these, 737 (92%) were men. The mean age was 32.9 years (±10.1 years). Most (561, 70%) were on antiretroviral treatment. The mean estimated glomerular filtration rate (eGFR) calculated according to Modification of Diet in Renal Disease (MDRD)-4 was 113.0 mL/min (±22.6). Comorbidities included diabetes mellitus (10, 1.3%) and hypertension (17, 2.1%). The prevalence of proteinuria detected by PRS was 8.3% (n = 66) and by uPCR 10.6% (n = 85). The concordance assessed by phi correlation coefficient was 0.70, p < 0.001, with a sensitivity of 51.7% (95% confidence interval [CI] 41%–62%) and specificity 97% (95% CI 39%–97%).ConclusionsThere is a high concordance between detection of proteinuria by PRS and uPCR. Therefore, in low-income countries PRS can be helpful for detecting tubular damage in people infected with HIV.

Monocyte activation, but not microbial translocation, is independently associated with markers of endovascular dysfunction in HIV-infected patients receiving cART.

Microbial translocation has been suggested as a driver of cardiovascular disease in HIV infection. We hypothesized that microbial translocation and the resulting monocyte activation would be associated with markers of endovascular dysfunction. In 60 HIV-infected patients on combination antiretroviral therapy, plasma levels of lipopolysaccharide, soluble CD14 (sCD14), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were measured. ADMA and SDMA were associated with sCD14 but not lipopolysaccharide. There was a significant increase in ADMA and SDMA through tertiles of sCD14, and both markers were associated with sCD14 in multivariate linear regression analyses. Monocyte activation as measured by sCD14 is associated with endovascular dysfunction in HIV infection.