Levels In HIV-infected Patients Research Articles

EFFECT OF THE DEGREE OF IMMUNOSUPPRESSION AND HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON SERUM IL-17 AND IL-10 LEVEL IN PATIENTS WITH HIV-INFECTION

We analyzed IL-17 and IL-10 serum levels in HIV-infected patients with different stage of disease, degree of immunodeficiency and treatment. We observed 70 patients with HIV infection. Among the patients studied 44 patients on antiretroviral therapy. HIV infection is marked increase in the concentration of IL-10, especially in patients with severe immunosuppression (CD4 200 ml-1). In HIV-infected patients with severe immunosuppression, which do not receive highly active antiretroviral therapy, there is an increase of IL-10 and IL-17 in serum, which may indicate a systemic immune activation.

Oral L-Arginine Modulates Blood Lactate and Interleukin-6 After Exercise in HIV-Infected Men

The acute administration of L-arginine (L-arg), a nitric oxide (NO) precursor, reduces lactate (LAC) concentration after exercise in healthy individuals. Lower concentration of L-arg may enhance the action of some inflammatory cytokines in HIV-1 infected patients. We tested the hypothesis that acute L-arg administration may reduce post-exercise blood LAC and inflammatory cytokines levels in HIV-infected patients. 10 HIV-infected men performed 2 maximal incremental cardiopulmonary exercise tests, separated by one week. 30 min before each test, patients received oral placebo or 20 g of L-arg, in random order. Blood LAC, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured before and up to 60 min after exercise. L-arg administration had no significant effect on exercise performance. Compared to placebo, L-arg administration reduced maximal post-exercise blood LAC from 8.7±0.6 to 6.9±0.4 mmol.L-1 (p<0.05). L-arg administration had no significant effect on TNF-alpha or IL-10 concentrations, but increased post-exercise IL-6 (placebo=19±3pg.mL-1; L-arg=63±8 pg.mL-1; p<0.05). In HIV-1 infected men, acute administration of L-arg reduces post-exercise blood LAC and increases IL-6 levels, suggesting the activation of the L-arg-NO pathway, with possible anti-inflammatory consequences.

Modeling interleukin-2-based immunotherapy in AIDS pathogenesis

In this paper, we sought to identify the CD4+ T-cell dynamics in the course of HIV infection in response to continuous and intermittent intravenous courses of interleukin-2 (IL-2), the principal cytokine responsible for progression of CD4+ T-lymphocytes from the G1 to the S phase of the cell cycle. Based on multivariate regression models, previous literature has concluded that the increase in survival of CD4+ T-cell appears to be the critical mechanism leading to sustained CD4+ T-cell levels in HIV-infected patients receiving intermittent IL-2 therapy. Underscored by comprehensive mathematical modeling, a major finding of the present work is related to the fact that, rather than due to any increase in survival of CD4+ T-cells, the expressive, selective and sustained CD4+ T-cell expansions following IL-2 administration may be related to the role of IL-2 in modulating the dynamics of Fas-dependent apoptotic pathways, such as activation-induced cell death (AICD) or HIV-specific apoptotic routes triggered by viral proteins.

Decreases in Inflammatory and Coagulation Biomarkers Levels in HIV-Infected Patients Switching from Enfuvirtide to Raltegravir: ANRS 138 Substudy

Stored plasma specimens from 164 participants in the ANRS 138 trial were analyzed to determine interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels at baseline and weeks 24 and 48. These virologically suppressed, treatment-experienced patients were randomly assigned to undergo an immediate switch (IS) or a deferred switch (DS; at week 24) from an enfuvirtide-based antiretroviral therapy (ART) regimen to a raltegravir-based regimen. At week 24, a significant decrease from baseline was observed in the IS arm, compared with the DS arm, for IL-6 level (-30% vs +10%; P < .002), hsCRP level (-46% vs +15%; P < .0001), and D-dimer level (-40% vs +6%; P < .0001). At week 48, there was a reproducible decrease in levels of all biomarkers in the DS arm.

SAT0352 Frequency of fractures and vitamin D serum levels in a cohort of HIV-1 infected patients

BackgroundAn increased risk of hypovitaminosis D and/or fractures in HIV-infected patients has been discussed. We investigated the frequency of fractures and vitamin D serum levels in HIV-infected patients in a...

Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.

Endothelial Progenitor Cells in HIV-Positive Patients

Endothelial Progenitor Cells in HIV-Positive Patients

AIDS and HIV Infection after Thirty Years.

AIDS and HIV Infection after Thirty Years.

HCV coinfection possibly promotes left ventricular dysfunction development

Hepatitis C virus (HCV) has been already linked to possible myocarditis and cardiomyopathy development. The brain natriuretic peptide (BNP) is a sensitive biomarker of left ventricular dysfunction. The present study aimed to evaluate the potential risk of cardiac injury in HIV-infected and HCV/HIV-coinfected patients with or without antiretroviral (ARV) therapy by comparing BNP serum levels in the groups studied. Eighty HIV-infected patients (65 men, 15 women, mean age 40 years; 29 with HCV coinfection, 48 on combined ARV therapy) were included in the cross-sectional study. BNP serum levels were evaluated by enzyme-linked immunosorbent assay. The BNP cut-off level for possible heart failure was 42 fmol/l as in an immunocompetent population. Seventy-eight (97.5%) patients studied had a BNP concentration above 42 fmol/l; seven patients (8.7%) had a concentration above 168 fmol/l associated with a worse outcome. There was no difference in the mean BNP serum levels in ARV-treated and untreated patients. However, the mean BNP serum level was significantly higher in HCV/HIV-coinfected patients in comparison with HIV-monoinfected patients (160.0 ± 130.9 vs. 81.9 ± 37.2 fmol/l; P<0.0001). There was no relationship between BNP serum levels and HIV viral load, CD4 cell count, sex, age, and abacavir or protease inhibitors use. A significant association was found between HCV coinfection and BNP serum level in HIV-infected patients. HCV coinfection possibly enhances the risk of left ventricular dysfunction development in this vulnerable population.

Impact of Antiretroviral Therapy on Glycemia and Transaminase Levels in Patients Living with HIV/AIDS in Limbe, Cameroon

This study aimed to determine the effect of antiretroviral therapy (ART) on glycemia and transaminase levels in HIV-infected patients in Limbe, Cameroon. A total of 200 ART-experienced patients and 30 ART-naive HIV-infected controls were recruited after submitting signed informed consent forms. The blood samples collected were screened for hepatitis B and C, and liver transaminases and random blood sugar (RBS) levels were determined spectrophotometrically. No significant correlation existed between the RBS and transaminase levels with either the duration of ART or the duration since HIV diagnosis. Although both groups of patients appeared to have similar transaminase and RBS levels, after controlling for confounders, patients on ART had significantly higher aspartate aminotransferase levels, significantly lower alanine aminotransferase levels, and slightly (but not significantly) lower glycemia levels (respective mean differences of 14.92 IU/L, P = .00; 11.95 IU/L, P = .00; and 7.60 mg/dL, P = .19). These changes need to be considered in monitoring patients on ART in this setting and other similar settings.

Hepatitis C virus co-infection and sexual risk behaviour are associated with a high homocysteine serum level in HIV-infected patients

A better understanding of the relationship of homocysteine with cardiovascular risk factors is needed. The objectives of this study were to assess the serum level of homocysteine in HIV-infected patients and to analyse the possible association of increased levels of the amino acid with cardiovascular risk factors, demographic and clinical characteristics of participants. Cross-sectional study carried out as a supplementary task to the usual controls necessary in HIV-infected patients in the outpatient clinic of the Hospital General of Castellon, Spain. For two consecutive visits the demographic, clinical and HIV-related characteristics and blood analyses results were obtained for each participant. Homocysteine serum level was documented and the possible association of the amino acid with all the other study variables was assessed with a multiple linear regression analysis. A total of 145 patients were included. The mean homocysteine serum level of all participants was 11.9 ± 5.9 µmol/L. A total of 54 patients (37%) presented homocysteine serum levels higher than the upper limit of normal. An association was found between higher homocysteine serum level and the following variables: family history of early coronary disease (P = 0.027), sexual HIV risk behaviour (P = 0.016), hepatitis C virus co-infection (P = 0.002), higher height (P = 0.002), higher diastolic blood pressure (P = 0.049), lower serum level of folic acid (P <0.001), and lower serum level of vitamin B12 (P = <0.001). In the HIV population, increased homocysteine serum level is associated with sexual risk behaviour and hepatitis C virus coinfection.

Longitudinal Assessment of Interleukin 7 Plasma Levels in HIV-Infected Patients in the Absence of and Under Antiretroviral Therapy

Cross-sectional studies in HIV-positive patients have suggested that interleukin 7 (IL-7) may increase in parallel to CD4 decline during the natural course of HIV infection. We tested this hypothesis in a longitudinal study examining the evolution of IL-7 and CD4 counts in 2 different scenarios. IL-7 and CD4 counts were regularly monitored in 30 drug-naive patients during a follow-up period of 46 ± 14 months in the absence of therapy and in 42 patients who started highly active antiretroviral therapy and maintained undetectable viremia for 2 years. Multivariate linear regression analysis was used to ascertain what factors were associated with IL-7 variations during follow-up. In antiretroviral therapy-naive patients, CD4 counts significantly decreased (P < 0.0001), whereas plasma HIV-RNA and IL-7 levels remained fairly stable. In patients on highly active antiretroviral therapy, CD4 counts significantly increased (P < 0.0001) and IL-7 tended to decrease (P = 0.1). There was no correlation between CD4 and IL-7 variations either in the naive or in the treated population. The only parameter significantly associated with IL-7 variation during follow-up was its baseline level that showed a negative correlation. In HIV patients with low or moderate degree of immunodeficiency, CD4 counts and plasma IL-7 levels do not evolve in parallel, suggesting that other factors different from CD4 counts must be involved in the upregulation of IL-7 observed in HIV infection.

Risk Factors for Vitamin D Deficiency in HIV-Infected Patients in the South Central United States

We evaluated the prevalence of serum 25-hydroxyvitamin D [25(OH)D] deficiency and the risk factors for vitamin D deficiency in HIV-infected patients in the South-Central United States. The study consisted of a cross-sectional assessment of vitamin D levels in HIV-infected patients receiving routine clinical care from a private practice in Houston, Texas (latitude 29°N). Vitamin D deficiency was defined as 25(OH)D less than 20 ng/ml (<50 nmol/liter). Two-hundred enrolled patients were surveyed with a vitamin D questionnaire to determine daily supplemental vitamin D intake, dietary vitamin D intake, and average sunlight exposure (minutes/day). Multivariate logistic regression analysis was used to determine significant risk factors for vitamin D deficiency. Median 25(OH)D was 15.5 ng/ml (interquartile range 10.9-24.6) for the total population (n=200). Approximately, two-thirds (64%) of patients had vitamin D deficiency and 20.5% had severe vitamin D deficiency [25(OH)D <10 ng/ml or <25 nmol/liter]. In univariate analysis, African-American race, current tobacco use, increased body mass index (BMI), lower serum calcium level, no supplemental vitamin D use, and low daily supplemental and total daily vitamin D intake were significantly associated with vitamin D deficiency. In multivariate analysis, African-American race [adjusted odds ratio (AOR) 3.53 (95% confidence interval (CI) 1.83-6.82)], higher BMI [AOR 1.07 (95% CI 1.002-1.139)], and low daily vitamin D supplemental intake [AOR 0.997 (95% CI 0.996-0.999)] were significantly associated with vitamin D deficiency. No HIV factors including antiretroviral class use were significantly associated with either vitamin D deficiency or severe vitamin D deficiency. Vitamin D deficiency and severe vitamin D deficiency were highly prevalent in this HIV population. In the HIV population, African-Americans or patients with a high BMI may benefit from vitamin D supplementation.

SNPs in the APM1 Gene Promoter Are Associated With Adiponectin Levels in HIV-Infected Individuals Receiving HAART

This study aimed to investigate the association between 4 polymorphisms in the leptin, leptin receptor, and adiponectin (APM1) genes and the occurrence of lipodystrophy and dyslipidemia in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Genotypes of 410 HIV-infected patients on HAART were investigated. Anthropometric (weight, height, waist circumference and skinfolds thickness) and biochemical (blood lipids, glucose, leptin, and adiponectin levels) parameters were evaluated. Genotype frequencies were compared between patients with or without lipodystrophy. Mean biochemical and anthropometric parameters were compared between the different genotypes. Lipodystrophy prevalence was 53.4%. Genotype frequencies were not different between patients with or without lipodystrophy. Carriers of the A allele for the APM1-11391 G.A and of the C allele for APM1-11377 C.G presented higher adiponectin levels compared to other genotypes, and carriers of the -11391A-11377C haplotype when compared with carriers of other haplotypes. SNPs in APM1 gene are associated with adiponectin levels in HIV-infected patients receiving HAART and may thus affect the occurrence of metabolic alterations in these patients. No influence of the leptin and leptin receptor gene polymorphisms on the occurrence of lipodystrophy and dyslipidemia was observed.

Short Communication: Contribution of the Immunovirological State and Traditional Cardiovascular Risk Factors to Low HDL-Cholesterol in HIV Patients

The prevalence of low HDL-C levels in an HIV population and its related factors was investigated. We undertook a multicenter, cross-sectional study of all HIV patients on regular follow-up in five hospitals (Southern Spain). A physical examination and fasting laboratory analysis were performed and a questionnaire about cardiovascular risk factors was provided. One thousand and seventy-two patients were included, 43.8% of whom had low HDL-C levels. The prevalence of low HDL-C was higher among patients diagnosed with AIDS, those not on antiretroviral therapy, those with a detectable HIV viral load, those with CD4 cell counts ≤350 cells/μl, smokers, and those with hypertriglyceridemia. For patients on antiretroviral therapy, the prevalence of low HDL-C was higher for those on protease inhibitors than those taking nonnucleoside reverse transcriptase inhibitors. In the multivariate analysis, low HDL-C levels were associated with tobacco use (OR 1.37, 95% CI 1.04-1.8; p = 0.04), hypertriglyceridemia (OR 2.94, 95% CI 2.2-3.8; p < 0.00001), CD4 cells count ≤350 cells/μl (OR 1.74, 95% CI 1.2-2.3; p < 0.0001), and a detectable HIV viral load (OR 1.85, 95% CI 1.3-2.5; p < 0.0001). The immunological and virological conditions, in addition to traditional cardiovascular risk factors such as tobacco use and hypertriglyceridemia, affect HDL-C levels in HIV-infected patients. For patients on antiretroviral therapy, the use of protease inhibitors is associated with a higher probability of low levels of HDL-C. Although it is not clear if the higher HDL-C levels associated with antiretroviral use are surrogates for decreased cardiovascular disease risk, this may be another reason to start antiretroviral therapy earlier.

Prevalence of Hyperapolipoprotein B and Associations with Other Cardiovascular Risk Factors Among Human Immunodeficiency Virus–Infected Patients in Pernambuco, Brazil

Hypertriglyceridemia associated with low high-density lipoprotein (HDL) levels and hypercholesterolemia is the most common metabolic disorder among human immunodeficiency virus (HIV)-infected patients using antiretroviral therapy. This atherogenic profile is associated with increased cardiovascular risk among these patients. Apolipoprotein B (apoB) is a better parameter than low-density lipoprotein (LDL) for evaluating lipids and cardiovascular risk among patients with diabetes and metabolic syndrome, but studies of apoB among HIV-infected patients are scarce. A cross-sectional study was conducted to estimate hyperapolipoprotein B (hyperapoB) prevalence and its association with other factors among HIV-infected patients attended in Recife, Pernambuco, Brazil. The prevalence of hyperapoB was 32.4% among 256 patients (62.1% male), with 90 mg/dL as the cutoff point. It was associated with prolonged use (>3 years) of antiretroviral therapy [odds ratio (OR), 3.63; 95% confidence interval (CI), 1.24-10.6], hypertriglyceridemia (OR, 2.45; 95% CI, 1.22-4.91), insulin resistance according to homeostasis model assessment of insulin resistance (HOMA-IR) (OR, 2.12; 95% CI, 1.03-4.35), past history of diabetes (OR, 3.58; 95% CI, 1.0-12.7), and hypertension (OR, 1.98; 95% CI, 0.92-4.28). It was not associated with low HDL levels or self-report lipodystrophy. ApoB was higher in patients with metabolic syndrome according to the National Cholesterol Education Program (NCEP) criteria and in those with higher Framingham scores. ApoB is a good parameter for evaluating lipid levels in HIV-infected patients with hypertriglyceridemia, among whom LDL measurements may not be appropriate. ApoB might be useful for diagnosing and treating hypertriglyceridemia in this population. The association between hyperapoB and hypertriglyceridemia and diseases relating to insulin resistance among HIV-infected patients suggests that this group of patients presents higher cardiovascular risk.

Measuring depression levels in HIV-infected patients as part of routine clinical care using the nine-item Patient Health Questionnaire (PHQ-9)

Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the nine-item Patient Health Questionnaire (PHQ-9) from the PRIME-MD. The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex; and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework.

Host–pathogen interactions in the development of metabolic disturbances and atherosclerosis in HIV infection: The role of CCL2 genetic variants

Background: Circulating CCL2 concentration has been implicated in promoting atherosclerosis in patients infected with HIV. We evaluated whether CCL2 gene variants are associated with metabolic disturbances and plasma CCL2 levels in HIV-infected patients. Methods and results: CCL2 genotypes and estimated haplotypes, plasma CCL2 levels and indicators of metabolic status in HIV-infected patients were compared with a representative group of the general population. We also performed a carotid/femoral artery ultrasonography to detect sub-clinical atherosclerosis in these patients. Six haplotypes were estimated in more than the 5% of individuals, and accounted for more than 98% of the population. In HIV-infected patients, carriers of H1, H2 and H5 haplotypes had higher CCL2 concentration than carriers of H3, H4 and H6 haplotypes. However, only carriers of H1 and H5 haplotypes presented higher insulin resistance as well as higher proportion of patients affected with sub-clinical. Conversely, carriers of H2 haplotype, which also showed high plasma CCL2 concentration, were associated with less deleterious metabolic disturbances. Conclusions: Our data are consistent with the hypothesis that the genetic background of the host is involved in CCL2 production and that this chemokine is implicated in promoting metabolic disturbances and sub-clinical atherosclerosis in HIV-infected patients.

Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART (P<0.001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive T(regs) were elevated significantly in HIV-infected patients (P<0.001) and were associated with thymic output measured as the T(REC) frequency in CD4(+) cells (P=0.038). In summary, T(reg) levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive T(regs) may contribute to higher T(reg) levels in HIV-infection.

Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy

Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (T(regs))] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the T(reg) level in HIV-infected patients we have conducted a prospective study enrolling treatment-naive HIV-infected patients just prior to starting treatment with HAART, measuring levels of T(regs) by flow cytometry and mRNA expression of forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this prospective study neither the percentage of CD4(+)CD25(high+) nor the expression of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV patients have higher T(regs) measured as percentages of CD4(+)CD25(high+) cells paralleled by higher levels of FoxP3 compared with healthy controls. The elevated level of T(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients.