Group Of HIV-infected Individuals Research Articles

HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p.

HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. A total of 32 HIV patients and 10 controls were recruited. Of HIV+individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.

Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers.

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals.

Immune activation markers in individuals with HIV-1 disease and their correlation with HIV-1 RNA levels in individuals on antiretroviral therapy

BackgroundCurrently CD4+ T lymphocyte counts and HIV-1 RNA levels are being utilized to predict outcome of human immunodeficiency virus (HIV) disease. Recently, the role of immune activation in HIV disease progression and response to treatment is being investigated. This study focused on the expression of CD38 and HLA-DR on lymphocyte subsets in various groups of HIV-infected individuals and to determine their association with HIV-1 disease progression. MethodsNinety-eight cases of patients with HIV/AIDS in different disease stages and twenty-four healthy HIV-negative individuals were included in the cross-sectional study. Their immune function and abnormal immune activation markers (CD38 & HLA-DR) were detected using a flowcytometer, and HIV-1 RNA levels in individuals receiving antiretroviral drugs were estimated. ResultsThe immune activation marker levels were significantly different between patients with different disease stages (P < 0.001). A significant negative correlation was observed between peripheral blood CD4+ T cell counts and immune activation markers. Also, a significant positive correlation was observed between HIV-1 RNA levels and CD38+CD8+ T lymphocyte. ConclusionImmune activation markers (CD38 & HLA-DR) increase with disease progression. CD38+ on CD8+ T lymphocyte correlates well with HIV1 RNA levels in individuals failing on antiretroviral therapy.

Restoring Cytokine Balance in HIV-Positive Individuals with Low CD4 T Cell Counts

HIV infects and destroys CD4+ T cells leading to a compromised immune system. In a double-blinded study, a group of HIV-infected individuals with CD4+ T cell counts below 350 cells/mm3 were given either an empty liposomal supplement or a liposomal glutathione (L-GSH) supplement to take over a 3-month period. Baseline measurements in HIV-positive subjects show a significant decrease in levels of interleukin (IL)-12, IL-2, and interferon (IFN)-γ, along with a substantial increase in the levels of IL-6, IL-10, transforming growth factor (TGF)-β, and free radicals, compared to healthy individuals. Supplementation of HIV-positive subjects with L-GSH for 3 months resulted in a notable increase in the levels of IL-12, IL-2, and IFN-γ, with a concomitant decrease in the levels of IL-6, IL-10, and free radicals, and stabilization in the levels of TGF-β, IL-1, and IL-17, compared to their placebo counterparts. Levels of free radicals in CD4+ T cells stabilized, while GSH levels increased in the treatment group. Those in the placebo group showed no significant difference throughout the study. In summary, supplementation with L-GSH in HIV-infected individuals with CD4+ T cell counts below 350 cells/mm3 can help restore redox homeostasis and cytokine balance, therefore aiding the immune system to control opportunistic infections.

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection.

To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. AHI (n = 33) and CHI (n = 34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow-up on cART in a subset of these individuals [6 months in AHI participants (n = 24), 1 year in CHI participants (n = 10)]. Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/l; P = 0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/l; P = 0.003). In untreated CHI, YKL-40 correlated with neopterin (r = 0.51, P = 0.0025), chemokine (CXC-motif) ligand-10 (r = 0.44, P = 0.011), and neurofilament light chain (r = 0.56, P = 0.0008) in CSF. This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.

Transmission clustering among newly diagnosed HIV patients in Chicago, 2008 to 2011: using phylogenetics to expand knowledge of regional HIV transmission patterns.

HIV transmission cluster analyses can inform HIV prevention efforts. We describe the first such assessment for transmission clustering among HIV patients in Chicago. We performed transmission cluster analyses using HIV pol sequences from newly diagnosed patients presenting to Chicago's largest HIV clinic between 2008 and 2011. We compared sequences through progressive pairwise alignment, using neighbor joining to construct an unrooted phylogenetic tree. We defined clusters as >2 sequences among which each sequence had at least 1 partner within a genetic distance of ≤1.5%. We used multivariable regression to examine factors associated with clustering and used geospatial analysis to assess geographic proximity of phylogenetically clustered patients. We compared sequences from 920 patients, median age of 35 years, 75% male, 67% black, 23% Hispanic, and 8% had a rapid plasma reagin titer ≥1:16 concurrent with their HIV diagnosis. We had HIV transmission risk data for 54%; 43% identified as men who have sex with men (MSM). Phylogenetic analysis demonstrated 123 patients (13%) grouped into 26 clusters, the largest having 20 members. In multivariable regression, age <25, black race, MSM status, male gender, higher HIV viral load, and rapid plasma reagin ≥1:16 associated with clustering. We did not observe geographic grouping of genetically clustered patients. Our results demonstrate high rates of HIV transmission clustering, without local geographic foci, among young black MSM in Chicago. Applied prospectively, phylogenetic analyses could guide prevention efforts and help break the cycle of transmission.

Decreased whole blood RNA expression of cathelicidin in HIV-infected heroin users in Bandung, Indonesia.

The antimicrobial peptide cathelicidin is critical in killing pathogens by innate immune cells, including Mycobacterium tuberculosis and Candida albicans. These pathogens often cause infections in opioid users, a risk that is greatly increased with concurrent human immunodeficiency virus (HIV) infection. Therefore, we examined the association between opioid use and cathelicidin in HIV-infected subjects from Bandung, Indonesia. The following three groups of HIV-infected individuals were included: (i) Active drug users: used heroin in the last 30 days; (ii) Methadone clients: received methadone maintenance therapy in the last 30 days; and (iii) never used opioids or did not use opioids in the year preceding inclusion. In addition to interviews, blood samples were taken to examine the RNA expression of cathelicidin. We found that the RNA expression of cathelicidin was significantly decreased (p=0.007) in heroin users, compared with controls. Opioids are associated with immunosuppression, and cathelicidin could be an important factor in this association. However, more research is needed to examine the direct effects of decreased cathelicidin levels.

HIV infection duration, social support and the level of trauma symptoms in a sample of HIV-positive Polish individuals

The aim of this study was to investigate the relationship between the average HIV infection duration and the level of quantitatively rated post-traumatic stress disorder (PTSD) symptoms and social support dimensions in a sample of 562 Polish HIV+ adults. Possible moderating effects of social support on the relationship between the average HIV infection duration and the level of PTSD symptoms were also analysed. The results of this study suggest that the average HIV infection duration may intensify PTSD symptoms and deteriorate the perceived availability of social support in HIV+ individuals. However, a positive relationship between HIV infection duration and the level of trauma symptoms was observed only in the group of HIV+ individuals with low perceived available social support, but not in the group of HIV-infected individuals with high perceived available social support. This research provided some new insight into the psychological and social aspects of living with HIV. In particular, our results suggest that although HIV infection duration may intensify trauma symptoms and deteriorate social support, perceived available social support may act as a buffer against HIV-related trauma symptoms.

QTc interval prolongation in HIV-infected patients: a case–control study by 24-hour Holter ECG recording

BackgroundAim of the study was to assess QTc interval by a 24-hour ECG recording in a group of HIV-infected individuals with a basal prolonged QTc. The risk factors associated with QTc prolongation and the indices of cardiovascular autonomic control were also evaluated.MethodsA case–control study was performed using as cases 32 HIV-infected patients with prolonged (>440 msec) QTc interval as assessed by Holter ECG, and as controls 64 HIV-infected subjects with normal QTc interval. Autonomic function was evaluated by heart rate variability analysis during 24-hour recording.ResultsDuration of HIV disease was significantly longer among cases than among controls (p=0.04). Waist/hip ratio was also higher among cases than among controls (p=0.05). Frequency domain analysis showed the absence of physiologic decrease of low frequency (LF) in the night period in both cases and controls. The LF night in cases showed a statistically significant reduction when compared with controls (p=0.007).ConclusionsIn our study group, QTc interval prolongation was associated with a longer duration of HIV infection and with a greater waist/hip ratio. HIV patients with QTc interval prolongation and with a longer duration of HIV infection were more likely to have an impairment of parasympathetic and sympathetic cardiac component.

Physical Activity, HIV, And Cardiovascular Disease Risk

The life expectancy for people living with HIV/AIDS (PLWHA) has increased due predominantly to advances in antiretroviral therapy (ART). However, these drugs in conjunction with the HIV infection and poor lifestyle choices have increased the prevalence of metabolic and anthropomorphic abnormalities that accelerates the progression of atherosclerosis and increases the risk of cardiovascular disease (CVD). PURPOSE: The purpose of this study was to determine the effects of moderate physical activity on CVD risk factors in a group of HIV-infected individuals. METHODS: 114 individuals were randomized to a physical activity group (PA) or non-exercise control group (CON). PA participated in a 6-week program consisting of two weekly 30 minute bouts of moderate intensity physical activity and 30 minute bouts of resistance training. CON attended the research center for the equivalent amount of time and were allowed to read or watch television. A graded exercise stress test and blood analysis was performed before and after the physical activity program for each participant. Repeated measures ANOVA was used to compare variables within groups, with between group analysis using ANOVA/Tukey post-hoc analysis. RESULTS: Baseline aerobic capacity across groups was approximately 25% below age and gender predicted levels. PA participants showed a 21% increase in aerobic capacity. Baseline blood analysis placed the average triglyceride level in the borderline high range. PA showed a significant reduction in triglycerides (155±70 to 110±30 mg/dl) with no change in the CON participants. CONCLUSION: The results indicate that even moderate doses of physical activity can increase aerobic capacity and reduce serum triglyceride levels. These findings suggest that physical activity can significantly affect important risk factors for CVD in people living with HIV/AIDS.

Dietary adequacy of HIV infected individuals in north India - A cross-sectional analysis

Background & objectives:Dietary inadequacy is common in developing countries and so is in immune-deficient HIV infected individuals. Hence, an assessment of dietary patterns was done among a group of HIV infected individuals and compared with recommended dietary allowances.Methods:One hundred consecutive HIV infected individuals were interviewed from the Immunodeficiency Clinic of a tertiary care center at Chandigarh. Dietary intake was assessed by 24 h recall method. Mean carbohydrate, protein and fat intakes were evaluated. Mean difference in the calorie intake from recommended dietary intake was then calculated. Mean absolute CD4 cell count was calculated and correlated with BMI and mean calorie intake.Results:Mean weight and BMI of the individuals participated in the study was 58.6 ± 11.7 (range, 34 - 94) kg and 21.5 ± 3.7 (range, 13.6 - 36.7) kg/m2, respectively. Mean total calories intake was 1713 ± 292.8 (860 - 2525) calories/day and mean difference in the calories taken from the standard values was 249.5 ± 190.7 (10.6 - 967.5) calories/day. There was no significant correlation between CD4 cell count and total calories taken.Interpretation & conclusions:In HIV-infected individuals the energy intake was significantly lower than the recommended average intake. Hence, efforts should be taken to ensure that HIV-infected individuals have access to high-quality, nutritious food choices that promote optimal dietary patterns.

Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection

Increased levels of activated T cells are a hallmark of the chronic stage of human immunodeficiency virus (HIV) infection and are highly correlated with HIV disease progression. We evaluated chloroquine (CQ) as a potential therapy to reduce immune activation during HIV infection. We found that the frequency of CD38(+) HLA-DR(+) CD8 T cells, as well as Ki-67 expression in CD8 and CD4 T cells, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.

Are women a different group of HIV-infected individuals?

Are women a different group of HIV-infected individuals?

Effect of HIV duration on ambulatory blood pressure in HIV-infected individuals with high office blood pressure

Objective. There is a scarcity of data on ambulatory blood pressure (ABP) in HIV-infected individuals. The aim of the study was to identify possible predictors of ABP in HIV-infected individuals. Methods. From a cohort of 542 HIV-infected patients, ABP monitoring was undertaken in 77 patients with high office blood pressure (BP) readings and without antihypertensive treatment. Results. 24-h and daytime ABPs were associated with HIV duration (r=0.24–0.33, p=0.004–0.033), but not with duration of combined antiretroviral therapy. In multivariate linear regression analyses with the different ABPs as dependent variables, HIV duration (unstandardized β=0.41–0.89, p=0.008–0.045) and log-transformed urinary albumin excretion (p=0.003–0.043) were predictors of all 24-h and daytime ABPs. Multiple logistic regression analysis revealed HIV duration (OR=1.14/year (95% CI 1.03–1.26)) as predictor of hypertension defined according to daytime ABP. Nocturnal hypertension was observed in 81%, white coat hypertension was present in 26%. Conclusions. HIV duration was an independent predictor of ABP and hypertension in a selected group of HIV-infected individuals. Nocturnal hypertension was prevalent, and white coat hypertension was present in one fourth of the patients.

Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study

IL-21 is a relatively newly discovered immune-enhancing cytokine that plays an essential role in controlling chronic viral infections. It is produced mainly by CD4(+) T cells, which are also the main targets of HIV-1 and are often depleted in HIV-infected individuals. Therefore, we sought to determine the dynamics of IL-21 production and its potential consequences for the survival of CD4(+) T cells and frequencies of HIV-specific CTL. For this purpose, we conducted a series of cross-sectional and longitudinal studies on different groups of HIV-infected patients and show in this study that the cytokine production is compromised early in the course of the infection. The serum cytokine concentrations correlate with CD4(+) T cell counts in the infected persons. Among different groups of HIV-infected individuals, only elite controllers maintain normal production of the cytokine. Highly active antiretroviral therapy only partially restores the production of this cytokine. Interestingly, HIV infection of human CD4(+) T cells inhibits cytokine production by decreasing the expression of c-Maf in virus-infected cells, not in uninfected bystander cells. We also show that the frequencies of IL-21-producing HIV-specific, but not human CMV-specific, Ag-experienced CD4(+) T cells are decreased in HIV-infected viremic patients. Furthermore, we demonstrate in this study that recombinant human IL-21 prevents enhanced spontaneous ex vivo death of CD4(+) T cells from HIV-infected patients. Together, our results suggest that serum IL-21 concentrations may serve as a useful biomarker for monitoring HIV disease progression and the cytokine may be considered for immunotherapy in HIV-infected patients.

Common problems with antiretroviral therapy among three Swedish groups of HIV infected individuals

The main objective of this study was to identify and compare the common problems and difficulties associated with combination antiretroviral therapy (CART) as experienced by three major groups of HIV infected individuals (homo- or bisexuals, former injecting drug users and origins of Sub-Saharan Africa) in Sweden. Based on the results from in-depth interviews with 15 representatives from the three major groups, a questionnaire was designed for use in a problem detection study (PDS). The study was conducted with 195 HIV-positive patients residing in the major cities of Sweden. The overall response rate was 79%. The problems identified in all three groups were negative attitudes from the public, worries about disease progression or therapy failure, medication or drug-related problems and problems in connection to pharmacy visits. A specific problem in the homo- or bisexual group was drug-related problems such as adverse effects, drug interactions and pill burden. For former injecting drug users, the specific problem was disease-related conflicts with relatives and the problem of coping with the social and psychological burden caused by the HIV infection. The African group termed the risk of exposing their medication at the pharmacy as a specific problem, as this could reveal their HIV status. Our findings regarding problems with CART in three patient groups in Sweden may be of use to tailor pharmacy care to HIV infected individuals. General strategies to improve adherence need to be complemented with approaches that will address the specific needs for the different patient groups affected by HIV. Further studies on group-specific interventions that promote concordance and adherence to CART will be necessary to minimize therapy failure and viral resistance.

Role of antiretroviral treatment in prolonging QTc interval in HIV-positive patients

The aims of our study were to assess the prevalence of QTc prolongation in a group of HIV-infected individuals and to evaluate the associated risk factors. All the 650 HIV-infected patients followed up at our outpatient clinic underwent ECG recording. A "nested" case-control study was performed using as cases 64 HIV-infected patients with QTc > 0.44 s and as controls (1:4) 256 HIV-positive subjects matched by gender and age with QTc interval < or = 0.44 s. A prolonged QTc interval was found in 9.8% of HIV-positive individuals (64/650). In the nested case-control study, an increased risk of having a prolonged QTc interval was observed among patients taking nelfinavir, efavirenz, methadone, cotrimoxazole or an excessive amount of alcohol. When a zidovudine (AZT)-containing backbone was associated with nelfinavir-based or efavirenz-based antiretroviral therapy, the risk of having a prolonged QTc interval was about three times higher than in patients taking nelfinavir or efavirenz without AZT. Several drugs administered to HIV-infected patients may cause a QTc interval prolongation increasing the risk of serious arrhythmias. An ECG follow-up for the assessment of QTc seems to be advisable for HIV-infected patients receiving drugs with a QTc prolonging potential.

Comparison CCR5del32 Mutation in the CCR5 Gene Frequencies in Russians, Tuvinians, and in Groups of HIV-Infected Individuals

The 32-bp deletion (CCR5del32 mutation) in the CCR5 (chemokine (C-C motif) receptor 5) gene, encoding CCR5 chemokine receptor, is one of the factors determining natural resistance to human immunodeficiency virus (HIV-1) infection. In the present study, the samples of Russians (n = 107), Tuvinians (n = 50), and HIV-infected individuals were examined for the presence of CCR5del32 mutation in the CCR5 gene. The CCR5del32 allele frequency in Russians and Tuvinians constituted 7.84 and 2%, respectively. Among HIV-1 infected individuals, two groups, of macrophage-tropic HIV-1 strain- and T-cell-tropic HIV-1 strain-infected were distinguished. The CCR5del32 allele frequency in the first group (6.45%) was lower than in the second one (8.73%). Statistical treatment of the HIV-1 infected individuals typing data showed that the difference in the CCR5del32 allele frequencies between the groups of sexually (macrophage-tropic) and parenterally (T-cell-tropic) infected individuals observed was within the limit of random deviation.

Effect of octreotide on small intestinal motility in HIV-infected patients with chronic refractory diarrhea.

Octreotide has been used to treat HIV-associated diarrhea. We aimed to assess the effect of octreotide on small intestinal motility in a group of HIV infected individuals with chronic diarrhea. Small intestinal motility was measured continuously for 48 hr by ambulatory strain gauge manometry in 12 HIV seropositive subjects with chronic diarrhea. During the second 24-hr period, intravenous octreotide was administered (100 microg every 8 hr). Postprandial and nocturnal fasting motility data were compared before and during administration of octreotide. Octreotide was associated with increased numbers of migrating motor complexes (MMCs) (7.25 vs 4.92, P = 0.03), and a relative decrease in the duration of phase II (22% vs 49.8, P = 0.03) during nocturnal fasting activity. Postprandial activity was absent in half of the subjects and the duration significantly reduced in the remainder. In conclusion, octreotide has a significant effect on small intestinal motility in HIV-infected individuals with diarrhea, which may influence intestinal transit.

Preventive therapy for tuberculosis in HIV-infected persons: analysis of policy options based on tuberculin status and CD4+ cell count. Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA).

Background To facilitate decisions about the possible implementation of isoniazid preventive therapy (IPT) for human immunodeficiency virus (HIV)–infected persons on a large scale, the benefits and associated costs of various policy options of IPT should be evaluated. Methods Variable values based mainly on a prospective cohort study performed in Italy were used in an epidemiological model to assess the effects of the administration of IPT to the following groups of HIV-infected individuals: (1) tuberculin positive; (2) anergic, with various levels of immunosuppression; and (3) all HIV-infected individuals. The calculations of the costs associated with each policy option were based on the situation within the Italian national health care system. Outcome measures were average cohort survival times, total quality-adjusted life years lived in the cohort, total economic costs, and marginal costs per marginal quality-adjusted life year saved for each policy option. Results Median life expectancy gains from IPT were 104 to 149 days for tuberculin-positive individuals and 19 to 27 days for anergic patients. The largest gains were achieved for individuals with the lowest levels of immunosuppression. For tuberculin-positive individuals, savings from a reduced number of active tuberculosis cases were greater than the costs of the intervention, even for low patient compliance levels. Preventive therapy for anergic persons can result in cost reductions at levels of tuberculosis infection of 15% or higher for a compliance level of at least 95%. For infection levels of less than 10%, cost-effectiveness ratios are unfavorable. Conclusions Isoniazid preventive therapy administered to tuberculin-positive, HIV-infected patients increases life expectancies and reduces medical costs. Its extension to anergic patients may be justifiable on economic grounds in populations with a high prevalence of tuberculosis infection.