Different Stages Of HIV Infection Research Articles

Features of Tat Protein in HIV-1 Sub-Subtype A6 Variants Circulating in the Moscow Region, Russia.

Tat, the trans-activator of transcription, is a multifunctional HIV-1 protein that can induce chronic inflammation and the development of somatic diseases in HIV-infected patients. Natural polymorphisms in Tat can impact the propagation of the inflammatory signal. Currently, Tat is considered an object for creating new therapeutic agents. Therefore, the identification of Tat protein features in various HIV-1 variants is a relevant task. The purpose of the study was to characterize the genetic variations of Tat-A6 in virus variants circulating in the Moscow Region. The authors analyzed 252 clinical samples from people living with HIV (PLWH) with different stages of HIV infection. Nested PCR for two fragments (tat1, tat2) with subsequent sequencing, subtyping, and statistical analysis was conducted. The authors received 252 sequences for tat1 and 189 for tat2. HIV-1 sub-subtype A6 was identified in 250 samples. The received results indicated the features of Tat1-A6 in variants of viruses circulating in the Moscow Region. In PLWH with different stages of HIV infection, C31S in Tat1-A6 was detected with different occurrence rates. It was demonstrated that Tat2-A6, instead of a functional significant 78RGD80 motif, had a 78QRD80 motif. Herewith, G79R in Tat2-A6 was defined as characteristic amino acid substitution for sub-subtype A6. Tat2-A6 in variants of viruses circulating in the Moscow Region demonstrated high conservatism.

Changing roles of CD3 + CD8 low T cells in combating HIV-1 infection.

Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low ) or high levels (CD8 high ) on HIV-1 replication inhibition after HIV-1 invasion into individual. Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 + CD8 low T cells and their counterpart CD3 + CD8 high T cells at different stages of HIV-1 infection. Compared with healthy donors, CD3 + CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 + CD8 low T cells gradually decreased. Simultaneously, CD3 + CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 + CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 - HLA-DR + CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 + CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 + CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 + CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 + CD8 low T cells, but comparable amounts of CD3 + CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 + CD8 low T cells than CD3 + CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Our findings suggest that CD3 + CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 + CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 + CD8 high T cells.

Aspects of HIV-associated cardiovascular pathology against the background of antiretroviral therapy

BACKGROUND: The detection of cardiovascular pathology in patients at various stages of HIV infection is highly relevant. Given the data presented in the scientific medical literature on the negative impact of this infection on the cardiovascular system (CVS), a higher level of mortality in this group of patients from cardiovascular diseases has recently increased several times.
 AIM: to identify cardiovascular pathology in patients at different stages of HIV infection (3 and 4), to determine the relationship with antiretroviral therapy (ART) regimens to improve the quality of medical care and disease prognosis.
 MATERIALS AND METHODS: We examined 60 patients (outpatient and inpatient) with HIV infection at different stages of the disease from June 2020 to December 2021. Retrospectively, an analysis was performed of electronic medical records of persons registered and observed at the MHC AIDS DZM (supervisor MD, prof. A.I. Mazus) based on the State Budgetary Healthcare Institution ICB No. 2 DZM. The following were analyzed: age, gender, medical history (terms of the disease, comorbidities), results of an objective examination, routine laboratory blood tests, and ART regimens. Cardiovascular pathology was identified by performing special instrumental diagnostics ECG, Echo-KG, and Doppler ultrasound of the brachiocephalic arteries followed by a consultation with a cardiologist in case of abnormalities. Categorical data were described with indications of absolute values and extensive indicators. Quantitative indicators were assessed for compliance with the normal distribution using the Shapiro-Wilk test and the Kolmogorov-Smirnov test. Statistical processing was performed using Microsoft Excel and StatTech v. 1.2.0. Differences were considered statistically significant at p 0.05.
 RESULTS: Based on the data presented, it can be noted that the observed group of HIV-infected patients was of middle age (41.38.5 years), and men accounted for 78%. Cardiovascular pathology was detected in 38 (63%), and stage 4 HIV infection was 71%. Among the pathologies of the heart, infective endocarditis (IE) with damage to the tricuspid valve (58%) was most often diagnosed, and most of them (77%) had stage 4 HIV infection. An analysis of the intake of ART showed that in patients who did not receive it for the entire period of the disease, such pathology was detected in 68.4% of cases; among patients with late initiation of ART or lack of adherence in 58% of cases; in those who received ART in a timely and regular manner, cardiovascular pathology was diagnosed five times less often in 11.8%, which indicates an obstructive effect of ART on the development of cardiovascular pathology in HIV infection. The statistical significance of the development of IE in the group of patients with intravenous use of PAS was revealed, which suggests the influence of drug addiction on the occurrence of heart pathology.
 CONCLUSION: The data obtained from this study may have specific practical significance, suggesting criteria for examining patients with HIV infection to identify cardiovascular pathology, which will affect the quality of medical care and the prognosis of the disease.

The altered metabolites contributed by dysbiosis of gut microbiota are associated with microbial translocation and immune activation during HIV infection.

The immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported. We conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples. The pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation. Metabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.

Alteraciones en la producción de citocinas en respuesta a Toxoplasma gondii aparecen desde las etapas tempranas en pacientes co-infectados con VIH-1.

Both HIV-1 and Toxoplasma gondii are able to invade central nervous system and affect its functionality. Advanced HIV-1 infection has been associated with defects in immune response to T. gondii, leading to reactivation of latent infections and the appearing of toxoplasmic encephalitis. This study evaluated changes in the immune response to T. gondii in different stages of HIV infection. Immune response to T. gondii was assessed studying cytokine production in response to parasite antigens in HIV-1-infected/T. gondii-non-infected (P1), HIV-1/T. gondii co-infected (P2), HIV-1-non-infected/T. gondii-non-infected (C1) and HIV-1-non-infected/T. gondii-infected (C2) individuals. Patients (P1 and P2) were divided in early/asymptomatic (P1A, P2A) or late/symptomatic (P1B/C, P2B/C) according to peripheral blood CD4+ T lympho-cyte counts (>350 or <350/μL, respectively). The HIV-1 infection, from early/asymptomatic stages, was associated with significant lower production of IL -2, TNF-α and IFN-γ in response to T. gondii, when P2 patients were compared with C2 controls. These early defects may impair anti-parasitic response in co-infect-ed patients, allowing to reactivation of parasitic latent infection, enhancing the risk of CNS damage and impairment of neurocognitive functions.

Analysis of the Characteristics of TIGIT-Expressing CD3-CD56+NK Cells in Controlling Different Stages of HIV-1 Infection.

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96−CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT−NK cells, while CD96+CD226− cells expanded. Reduced CD96−CD226+ cells and elevated CD96+CD226− cells among NK cells especially TIGIT−NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A−NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C−NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A−NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT−NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT−NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT−NK cells, except for TNF-α−CD107a+IFN-γ−NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

MAIT Cell Loss and Reconstitution in HIV-1 Disease.

Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin-related metabolites presented by the evolutionarily conserved MHC class I-related (MR1) molecule. MAIT cells are abundant in circulation and mucosal tissues and are poised to mount rapid effector responses against diverse microbial organisms. Despite the absence of virally encoded riboflavin-related metabolite antigens, MAIT cells can respond to viral infections in an MR1-independent and cytokine-dependent manner. In chronic HIV-1 infection, MAIT cells are persistently depleted and functionally exhausted. Long-term effective combination antiretroviral therapy can only partially rescue MAIT cell numbers and dysfunction. Our understanding of the mechanisms underlying MAIT cell loss in HIV-1 infection is still incomplete, and to date, few effective strategies to recover their loss in humans are available. Here, we review current knowledge concerning the mechanisms of MAIT cell responses and loss in different stages of HIV-1 infection and how we may potentially develop strategies to restore these cells in the clinical setting. We further discuss novel strategies that may aid future investigations into MAIT cell immunobiology in HIV-1 infection, including the potential use of three-dimensional organoid models to dissect the mechanisms of MAIT cell depletion and to explore interventions that may restore their numbers and functionality.

Childrens intestinal microbiocenosis at different stages of HIV infection

Childrens intestinal microbiocenosis at different stages of HIV infection

Introducing pre-exposure prophylaxis to prevent HIV acquisition among men who have sex with men in Sweden: insights from a mathematical pair formation model

ObjectivesSince 2017, the Public Health Agency of Sweden recommends that pre-exposure prophylaxis (PrEP) for HIV should be offered to high-risk individuals, in particular to men who have sex with men...

Higher Baseline ADCC Responses in Chronic Nonprogressive HIV Infection Are Associated with Reduced HIV Burden in Later Course of Disease.

The importance of anti-HIV antibodies mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in protective immunity against HIV is recognized recently. The purpose of this study was to measure the functional ADCC response at different stages of HIV infection in a well-defined HIV+ cohort, including 20 recently infected individuals, 30 with long-term slow-progressive, 24 with short-term slow-progressive and 32 with progressive HIV infection using a rapid fluorometric ADCC assay. The antibodies mediating ADCC were found in all disease stages. These antibodies were detectable at as early as 25 days after the estimated date of infection, however, did not influence the viral load set point probably indicating no major influence on the early course of the disease. However, the frequency and magnitude of functional ADCC responses were associated with higher CD4+T cell count and lower viral load and were significantly lower in progressors compared with other groups. The usefulness of the ADCC responses in longer viral control was assessed in a subset of participants with slowly progressing HIV infection. In these individuals, the ADCC responses observed at the visit 1 were found to be increased over time and were associated with lower plasma viral load estimated 4 to 15 years later in the disease course. Overall, the study findings confirm the role of ADCC antibodies in reducing the viral burden and also indicate the probable role of sustained functional ADCC responses in reducing the viral burden during the later period of HIV infection.

Immunological Changes in Monocyte Subsets and Their Association With Foxp3+ Regulatory T Cells in HIV-1-Infected Individuals With Syphilis: A Brief Research Report

The incidence of syphilis has increased dramatically in men who have sex with men (MSM), especially those with HIV-1 infection. Treponema pallidum and HIV-1 are bidirectionally synergistic, accelerating disease progression reciprocally in co-infected individuals. We have shown that monocytes have different effects on T helper cells at different stages of HIV-1 infection. However, the immunological changes in the three monocyte subsets and in regulatory T cells (Tregs), and the associations between these cell types during syphilis infection among HIV-1-infected MSM remain unclear. Herein, we used cell staining methods to explore changes in monocyte subsets and Tregs and any associations between these cells. We found that the frequency of classical monocytes was higher in the rapid plasma reagin (RPR+) group than in the healthy controls (HCs) and the chronic HIV-1 infection (CHI) plus RPR+ (CHI&RPR+) group. The frequencies of Foxp3+CD25+CD45RA+ and Foxp3+Helios+CD45RA+ Tregs were significantly higher in the RPR+, CHI, and CHI&RPR+ groups than in HCs, whereas the frequency of CD45RA+ Tregs was lower in the CHI&RPR+ group than in CHI group. The frequencies of Foxp3+CD25+CD45RO+ and Foxp3+Helios+CD45RO+ Tregs were lower in the RPR+, CHI, and CHI&RPR+ groups than in HCs. The frequency of intermediate monocytes was inversely correlated with the frequency of CD45RA+ Tregs and positively correlated with the frequency of CD45RO+ Tregs. These results demonstrate for the first time that intermediate monocytes control the differentiation of Treg subsets in Treponema pallidum/HIV-1 co-infections. These findings provide new insights into an immunological mechanism involving monocytes/Tregs in HIV-infected individuals with syphilis.

HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS: DIAGNOSIS, DETECTION OF CAUSES AND THERAPY EFFICIENCY

The lecture intended for general practitioners represents collated information on the most important mechanisms of brain damage under HIV infection, the rate of neurocognitive disorders and their role in disability of patients, classification of these disorders. The capabilities and importance of diagnosis and an in-depth work-up of patients for establishing complete clinical diagnosis and order of effective treatment are presented in the lecture. Much attention is given to immunosuppression influence, brain cell elements involvement and forming of reservoir of HIV infection in pathogenesis of neurocognitive diseases. The lecture describes special aspects of radiology examinations including magnetic resonance imaging, magnetic resonance spectroscopy for assessment of metabolism and tissue perfusion using some chemical markers. Approaches to prevention, diagnosis and treatment are provided taking into account the stage of a disease. An algorithm of detection of causes and diagnosis of cognitive disorders is stated in the lecture and the role of different diagnostic approaches at different stages of HIV infection including HIV-associated diseases is shown.

HIV DNA: a clinical marker of HIV reservoirs.

A number studies are currently underway to develop new drugs aimed at reducing the HIV reservoir or achieving ART-free control of HIV infection. Many markers of HIV reservoirs have been proposed, each one having a different meaning. Total HIV DNA dynamics during the course of HIV infection and its predictive value are now well known. This marker allowed to estimate the size of HIV reservoir at different stages of HIV infection in blood, cell subsets and tissues. Therefore, the purpose of this review is timely and relevant, with the objective to discuss how total HIV DNA might be helpful in the clinical settings. Among the markers, it appears that HIV DNA is the most well studied, and recent articles confirmed that this marker is easy to use and is precise, specific, practical, robust and reproducible. All these characteristics correspond to what is expected from a helpful clinical marker. HIV DNA level could be considered as a global marker, and it is usually included in current clinical studies to describe the persistence and dynamics of the HIV reservoir, mainly in treated patients. HIV DNA might be helpful in designing clinical trials and personalized medication for HIV patients in the future.

High CXCL10/IP-10 levels are a hallmark in the clinical evolution of the HIV infection

The aim of this study was to investigate the modulation of plasma CXCL10, CCL20, CCL22, CCL2, CCL17 and CCL24 levels in HIV-positive patients grouped according to extreme phenotypes of progression to AIDS, and at different stages of HIV infection. HIV-positive individuals with extreme phenotypes of AIDS progression (n=58) at different clinical stages (chronic individuals, both pre-HAART and under-HAART) and HIV-negative controls (n=20) were evaluated. Additionally, HIV-positive individuals that initiated HAART with >350CD4+T-cells/mm3 were compared with those who initiated treatment with <350CD4+T-cells/mm3. Plasma levels of six chemokines were quantified by a Luminex assay. Higher CXCL10 levels were observed in individuals immediately before their CD4+T-cell levels were indicative for HAART (pre-HAART), independently of their progressor status, i.e. slow (SPs) or rapid progressors (RPs). SPs pre-HAART showed higher CXCL10 levels compared to elite controllers and RPs under HAART (pc=0.009 and pc=0.007, respectively). CXCL10 levels were higher in SPs HAART CD4<350 (initiated HAART with <350 CD4+T-cells) when compared with SPs HAART CD4>350 (initiated HAART with >350 CD4+T-cells) (1096 vs. 360.33pg/mL, p=0.0101). Normalisation of CXCL10 levels seems to depend on the CD4+T-cell nadir at HAART initiation. CCL20 levels were higher in chronic SPs, SPs pre-HAART, SPs HAART and RPs HAART compared with the HIV-negative controls, indicating persistent CCL20 expression. In conclusion, our results indicate that CXCL10 levels are a hallmark in the clinical evolution of HIV infection. However, our results must be verified in a study evaluating a larger number of AIDS progressors.

Neurocognitive profile of patients with early stages of HIV infection

HIV-associated neurocognitive disorders (HAND) may include neurological disorders of various severities such as AIDS dementia complex (ADC) also known as HIV dementia and HIV-associated dementia (HAD), HIV encephalopathy, and Mild Neurocognitive Disorder (MND). As it seems HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. Despite of a group, evidences have described presence of cognitive alterations in HIV patients at different stages of HIV infection so far; little is known about the neurocognitive state of patients at very early stages of HIV infection. Here, we explored the neurocognitive profile of a group of cases of HIV patients at very early stages of HIV infection. We have analyzed of three groups of subjects, thus, we have studied a group of patients with early HIV infection, a healthy control group and a group of patients with mild cognitive impairment due to neurodegenerative causes. Our results suggested that cognitive processes are sensitive to very early neuropathological changes in HIV infection. Noteworthy, our results also showed that neurocognitive profile of HIV patients differs from those cognitive alterations in patients with mild cognitive disorders associated to primary neurodegeneration. Together, our results point out that HIV infection generates neural changes even at early stages of infection. Furthermore, our results highlight the importance of a deep neurocognitive exploration at very early stages of HIV infection as this approach allow improve the accompaniment, clinical attachment and interventions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Distribution and Activation of CD8+ T Cells in the Duodenal Mucosa before and after HIV Seroconversion.

CD8+ T cells in the intestinal mucosa influence the HIV-associated pathogenesis, but little is known about the dynamics of mucosal CD8+ T cell counts and activation of these cells during the course of infection. In this study, mucosal CD8+ T cells in the duodenum were studied at different stages of HIV infection, starting from the seronegative phase. In seronegative acute HIV infection, CD8+ T cell counts increased in the epithelium, but not in the lamina propria. Infiltration of the lamina propria by peripherally expanded CD8+ T cells was observed after seroconversion. Highest increase in the expression of perforin, the rate-limiting molecule for cytotoxic CD8+ T cell activity, was evident in the lamina propria of seronegative acutely HIV-infected patients. The number of perforin-expressing cells in the lamina propria of acutely HIV-infected patients was positively associated with biomarkers of enterocyte damage and microbial translocation. After seroconversion, perforin expression was downregulated in the lamina propria, but not in the epithelium. In conclusion, our findings demonstrate that intraepithelial and lamina propria CD8+ T cells exhibit different dynamics of numerical alteration and cytotoxic activity in HIV-infected patients. Moreover, our results suggest that perforin-dependent cytotoxic mechanisms by CD8+ T cells could impair the intestinal mucosal barrier already in the seronegative phase of acute HIV infection, thereby inducing microbial translocation as one of the earliest pathological events in HIV infection.

Discovering Perturbation of Modular Structure in HIV Progression by Integrating Multiple Data Sources Through Non-Negative Matrix Factorization.

Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information, and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF). As the identified meta-modules inherit those information so, detecting perturbation of these, reflects the changes in expression pattern, in PPI structure and in functional similarity of genes during the infection progression. To integrate modules of different data sources into strong meta-modules, NMF based clustering is utilized here. Perturbation in meta-modular structure is identified by investigating the topological and intramodular properties and putting rank to those meta-modules using a rank aggregation algorithm. We have also analyzed the preservation structure of significant GO terms in which the human proteins of the meta-modules participate. Moreover, we have performed an analysis to show the change of coregulation pattern of identified transcription factors (TFs) over the HIV progression stages.

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection

The aim of this study was to compare cytokine expression on both gene and protein levels in acute and chronic phase of HIV type 1 (HIV-1) infection. Thirty four patients were enrolled for cytokine expression analysis on protein level in acute and chronic stage of HIV-1 infection. Using PCR array technology, expression of 84 cytokine genes was measured in 3 patients in acute and 3 patients in chronic stage of HIV-1 infection. Bead-based cytometry was used to quantify levels of Th1/Th2/Th9/Th17/Th22 cytokines. The results showed statistically significant increase of 13 cytokine gene expression (cd40lg, csf2, ifna5, il12b, il1b, il20, lta, osm, spp1, tgfa, tnfsf 11, 14 and 8) and downregulation of the il12a expression in chronic HIV type 1 infection. Concentrations of IL-10, IL-4 and TNF-α were increased in the acute HIV type 1 infection when compared to control group. During chronic HIV type 1 infection there was an increase of IL-10, TNF-α, IL-2, IL-6, IL-13 and IL-22 levels when compared to control group. Comparison of cytokine expression between two stages of infection showed a significant decrease in IL-9 concentration. This study showed changes in cytokine profiles on both gene and protein levels in different stages of HIV-infection.

Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection.

Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals.

Higher Type 1 Interferon Levels in Plasma of Asymptomatic HIV-2 than in HIV-1 Individuals

A number of cytokines are secreted during HIV infection that enhances both innate and adaptive immune responses. Interferon-α/β/γ, IL-12, IL-15 and IL-18 have been found to contribute to the development, maturation, differentiation and function of NK and other immune cells. The levels of IFN-α/β/γ, IL-12, IL-15 and IL-18 were compared in the plasma of 90 HIV-1 infected and 90 HIV-2 infected subjects by ELISA or Cytometric Beads Array assays. The HIV-infected subjects were stratified according to CD4+ T cell counts into three groups: >500, 200 - 500 and <200 cells/ul, with 30 subjects in each group. Cytokine levels were also determined in the plasma of 50 HIV uninfected blood bank donors. Among the cytokines tested, IFN-α was found to be significantly increased in HIV-2 infected compared to HIV-1 infected subjects at high CD4+ T cell counts (p = 0.001). The levels of IFN-β were seen to differ between the two infections in patients from the category of medium CD4+ T cell counts: this was significantly increased in HIV-2 infected patients (p < 0.001) as well as compared to uninfected controls (p = 0.001). The levels of IFN-γ were similar at all the CD4+ T cell categories except for an increase in HIV-2 infected patients at low CD4+ T cell counts (p = 0.02). The levels of these cytokines were similar in all HIV-1 subjects. Also, the level of IL-12p70 was similar between the two infections but significantly higher in HIV-2 at low compared to medium CD4+ T cells categories (p = 0.047). Similar to IFN-γ and IL-12p70, the levels of both IL-18 and IL-15 were found to be significantly higher in HIV-2 infected patients compared to HIV-1 at low CD4+ T cell counts (p < 0.05). These data show that there is variability in the levels of innate cytokines at different stages of HIV infection but the finding of increased IFN-α in HIV-2 infected asymptomatic subjects is consistent with the high innate NK responses previously noted at this stage of infection.