Progression Of HIV Infection Research Articles

Clinical significance of B7-H3 expression in circulating CD4+CD25high T cells, CD14+ monocytes, and plasma for the progression of HIV infection

BackgroundB7-H3 is an important immune checkpoint molecule that plays a negative role in immune regulation. This study was aimed to explore B7-H3 expression in HIV-infected patients and its clinical significance.MethodsTo explore the expression and clinical significance of B7-H3 in HIV-infected patients, we investigated the B7-H3 expression pattern and the correlation of B7-H3 expression with clinical parameters of HIV-infected patients with different levels of CD4+ T cells. To assess the role of B7-H3 in regulating the function of T cells in HIV infection, we performed a proliferation assay and T cell function test in vitro.ResultsB7-H3 expression in HIV-infected patients was significantly higher than that in healthy controls. mB7-H3 expression on CD4+CD25high T cells and CD14+ monocytes increased with disease progression. mB7-H3 expression on CD4+CD25high T cells and monocytes was negatively correlated with lymphocyte count, CD4+T cell count, and positively correlated with HIV viral load in HIV-infected patients. when the number of CD4+ T cells in HIV-infected patients was ≥ 200/µL, sB7-H3 and mB7-H3 expression levels on CD4+CD25high T cells and monocytes were negatively correlated with lymphocyte count, CD4+T cell count. sB7-H3 and mB7-H3 expression on monocytes were positively correlated with HIV viral load. B7-H3 inhibited the proliferation of lymphocytes and the secretion of IFN-γ in vitro, especially the ability of CD8+ T cells to secrete IFN-γ.ConclusionsB7-H3 played an important negative regulatory role in anti-HIV infection immunity. It could be used as a potential biomarker for the progression of HIV infection and a novel target for the treatment of HIV infection.

Functional exhaustion of CD4<sup>+</sup>T cells in HIV/HCV coinfected HAART-treated patients

Infection with hepatitis C virus (HCV) is common among HIV-positive patients, with up to 50% of them being coinfected in Russia. While highly active antiretroviral therapy (HAART) suppresses HIV replication and restores the immune system of HIV-infected subjects, HCV coinfection interferes with CD4+T cell regeneration and increases the risk of patients’ morbidity and mortality. During HAART, HIVinfection progression and the immune system restoration efficiency largely depend on immune activation and CD4+T cell exhaustion. This study determined the level of activation, exhaustion, and cytokine production in CD4+T cells obtained from the peripheral blood of HAART-treated HIV/HCV coinfected and HIV monoinfected subjects. The study comprised 11 HIV/HCV coinfected individuals and 10 HIV monoinfected patients receiving HAART for more than two years, with a control group of 10 volunteers without the signs of HIV or HCV infections. Compared with healthy controls, HIV/HCV coinfected patients had an increased frequency of activated CD38+HLA-DR+ CD4+T lymphocytes (p < 0.05), a higher level of CD4+T cell exhaustion determined according to the TIGIT expression density per cell (p < 0.05), and a greater proportion of interferon-gamma (IFNγ)-producing CD4+T lymphocytes following activation (p < 0.05). The frequency of IFNγ-producing CD4+T cells in the donors’ blood positively correlated with the proportion of activated CD4+T cells (R = 0.514, p < 0.01). Despite having a large number of IFNγ-producing CD4+T lymphocytes, the HIV/HCV coinfected patients’ average production of IFNγ by CD4+T cells was significantly lower than that in healthy controls (p < 0.05). The IFNγ production in CD4+T lymphocytes did not depend on activation (p > 0.05). However, a negative correlation was established between the IFNγ production and the level of CD4+T cell exhaustion (R = -0.400, p < 0.05). The letter was also found to inversely correlate with the CD4+T cell counts in the donors’ peripheral blood (R = -0.598, p < 0.01). These data suggest that HCV coinfection leads to pronounced functional exhaustion of CD4+T cells and may aggravate the course of HIVinfection in patients receiving HAART.

Fabrication of DNA/2-thiobarbituric acid-osmium tetroxide/pencil graphite electrode and its application for the electrochemical determination of trace amounts of efavirenz

Efavirenz (EFA) is an antiviral drug that reduces the progression of HIV infection by reducing the virus's proliferation in the blood. This study used a pencil graphite electrode modified with deoxyribonucleic acid/2-thiobarbituric acid-osmium tetroxide (DNA/TBA-OsO4/PGE) to measure traces of the drug. The electrode surface was modified in two stages by the electrodeposition of thiobarbituric acid-osmium tetroxide and DNA, respectively. Electrode surface characterization was revealed by high-resolution scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Analytical figures of merit, such as the linear range over the concentration range of 1 × 10−12 to 1 × 10−5 M and the detection limit of 1.4 × 10−13 M, demonstrated that the modified DNA/TBA-OsO4/PGE is superior to the other proposed electrodes for the determination of EFA. Additionally, the modified electrode was used to measure EFA in blood, urine and water samples.

Cytomegalovirus viremia and advanced HIV disease: is there an argument for anti-CMV treatment?

ABSTRACT Introduction The role of cytomegalovirus (CMV) infection as a co-factor in HIV disease has been a topic of considerable interest since the beginning of the HIV pandemic. CMV is believed to function both as a co-factor in the progression of HIV infection, and as a contributor to enhanced disease for other opportunistic infections. Areas covered In this special article, we review several recent studies that have enhanced our understanding of the role that CMV infection plays in the natural history of other HIV-related opportunistic infections. We review the clinical evidence that demonstrates how CMV viremia has emerged as an independent risk factor for the progression of infections such as those caused by C. neoformans and M. tuberculosis. We outline the biological underpinnings of the various hypotheses by which CMV, as an immunomodulatory virus, may modify the natural history of HIV-related infections. Expert opinion Evidence suggests that active CMV replication, manifest as CMV viremia (DNAemia), may play a key role in driving progression of HIV-associated opportunistic infections. We propose that control of CMV replication, independent of the known benefit of HAART therapy on reducing CMV end-organ disease, could reduce the risk of disease and mortality attributable to opportunistic infections such as cryptococcosis and tuberculosis. This could be achieved by the targeted use of CMV antivirals. The advent of newer (and safer) orally bioavailable CMV antivirals has renewed interest in, and opportunities for, randomized controlled trials to evaluate CMV viremia as a modifiable risk factor in high-risk persons with HIV disease.

Identification of Molecular Mechanisms Involved in Viral Infection Progression Based on Text Mining: Case Study for HIV Infection.

Viruses cause various infections that may affect human lifestyle for durations ranging from several days to for many years. Although preventative and therapeutic remedies are available for many viruses, they may still have a profound impact on human life. The human immunodeficiency virus type 1 is the most common cause of HIV infection, which represents one of the most dangerous and complex diseases since it affects the immune system and causes its disruption, leading to secondary complications and negatively influencing health-related quality of life. While highly active antiretroviral therapy may decrease the viral load and the velocity of HIV infection progression, some individual peculiarities may affect viral load control or the progression of T-cell malfunction induced by HIV. Our study is aimed at the text-based identification of molecular mechanisms that may be involved in viral infection progression, using HIV as a case study. Specifically, we identified human proteins and genes which commonly occurred, overexpressed or underexpressed, in the collections of publications relevant to (i) HIV infection progression and (ii) acute and chronic stages of HIV infection. Then, we considered biological processes that are controlled by the identified protein and genes. We verified the impact of the identified molecules in the associated clinical study.

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.

Prevalence of, and factors associated with, alcohol use disorder among young adults (aged 15–24 years) living with HIV/AIDS in low-income and middle-income countries: protocol for a systematic review

IntroductionAlcohol use is a global driver of HIV infection and disease progression, mediated through risky behaviour and poor antiretroviral adherence. Most studies about the burden of alcohol use among people...

Biomarkers in a Cohort of HIV-Infected Patients Single- or Co-Infected with HTLV-1, HTLV-2, and/or HCV: A Cross-Sectional, Observational Study.

HIV, HTLV-1/-2, and HCV share routes of transmission, and such virus co-infections could account for worse outcomes of associated diseases. Measuring cytokines/chemokines, CD4 and CD8 T cells, and HIV viral load (VL) in HIV single-infected and co-infected individuals has prognostic value. We analyzed such biomarkers in 129 blood samples of HIV-infected individuals matched for age and sex and divided into six groups (G1 (69 HIV); G2 (9 HIV/HTLV-1); G3 (6 HIV/HTLV-2); G4 (11 HIV/HCV); G5 (19 HIV/HCV/HTLV-1); and G6 (15 HIV/HCV/HTLV-2)). Eight cytokines/chemokines from fifteen analytes could be compared. The highest levels of Th1 and pro-inflammatory cytokines were detected in G2 (IFN-γ) and G6 (IL-6 and IL1-β) and of chemokines in G1 (MIG, IP10, RANTES), G4 (MCP1), and G6 (MIP1-β). The highest CD4 cells number and the lowest HIV VL were identified in G3 and the opposite results in G2. Positive correlations between CD4 and CD8 cells counts and IL-6 levels were detected in G2 and G5 and of HIV VL and RANTES in G4. Negative correlations were detected between CD8 and IFN-γ in G4 and HIV VL and RANTES in G6. Despite the small number of the cohort analyzed, and although the cross-sectional study design does not allow firm conclusions, the homogeneity of the characteristics of HIV/HTLV-co-infected individuals regarding age, time and route of HIV acquisition, and criteria for introducing ART enable us to suggest a negative impact of HTLV-1 and a possible protective role of HTLV-2 in HIV infection progression in such patients.

FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation.

ObjectivesBesides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3+ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3+ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied.MethodsSubsets of FoxP3+ CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21).ResultsAcute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3+ CD8 T-cells, while early ART normalized only the frequencies of total FoxP3+ CD8 T-cells. We observed an increase in FoxP3+ CD8 T-cell immune activation (HLADR+/CD38+), senescence (CD57+/CD28-), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3+ CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3+ CD8 T-cells and CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3+ CD8 T-cell characteristics in uninfected individuals.ConclusionsAlthough early ART normalized total FoxP3+ CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cell, which may contribute to immune dysfunction.

Material Security Scale as a Measurement of Poverty among Key Populations At-Risk for HIV/AIDS in Malaysia: An Implication for People Who Use Drugs and Transgender People during the COVID-19 Pandemic.

The HIV epidemic is fueled by poverty; yet, methods to measure poverty remain scarce among populations at risk for HIV infection and disease progression to AIDS in Malaysia. Between August and November 2020, using data from a cross-sectional study of people who use drugs, (PWUD), transgender people, sex workers and men who have sex with men, this study examined the reliability and validity of a material security scale as a measurement of poverty. Additionally, we assessed factors associated with material security scores. We performed confirmatory factor analysis (CFA) for 268 study participants included in the analysis. A revised nine-item three-factor structure of the material security scale demonstrated an excellent fit in CFA. The revised material security score displayed good reliability, with Cronbach’s alpha of 0.843, 0.826 and 0.818 for housing, economic resources and basic needs factors, respectively. In a subsequent analysis, PWUD and transgender people were less likely to present good material security scores during the pandemic, compared to their counterparts. The revised nine-item scale is a useful tool to assess poverty among key populations at-risk for HIV/AIDS with the potential to be extrapolated in similar income settings.

Practical aspects of human immunodeficiency virus multiresistance in modern clinical practice

The article presents an analysis of a special clinical case: a male patient with perinatal HIV infection and the development of HIV multi-resistance to antiretroviral drugs. Multiple corrections of treatment regimens were carried out based on the results of determining HIV resistance to the antiretroviral drugs used. The treatment regimen included antiretroviral drugs with fundamentally new mechanisms of action for HIV, not registered in the Russian Federation. However, to date, in the patient with more than twenty years of experience in antiretroviral therapy, it has not been possible to achieve immunological and virological efficacy of treatment. There continues to be a persistent decrease in the indicators of the immune status and an increase in the viral load of HIV in the blood, the appearance of clinical symptoms of opportunistic diseases indicating the progression of HIV infection and an unfavorable vital prognosis, despite the use of various combinations of antiretroviral drugs. This observation demonstrates the difficulties in choosing an effective antiretroviral therapy, taking into account the established sensitivity of HIV to antiretroviral drugs and the possibility of their progredient administration. It is certainly necessary to analyze all ART regimens with the results of HIV resistance to antiretroviral drugs using to improve the effectiveness of therapy is in each case.

Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2

Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1, HIV-2 or dually HIV-1/HIV-2 infected individuals. In this study the gene encoding Interferon alpha-inducible protein 27 (IFI27) was found to be the most differentially expressed. Detailed expression analysis revealed significantly higher IFI27 expression in HIV infected individuals compared with seronegative individuals, irrespectively of HIV type. Moreover, IFI27 expression was higher in HIV-1 than in HIV-2 infected individuals. Multiple linear regression analysis, adjusting for age and sex, showed also that plasma viral load was the strongest predictor of IFI27 expression, followed by CD4% and HIV type. In line with this, IFI27 expression was found to be higher in HIV-2 viremic, compared with HIV-2 aviremic individuals. Still, HIV-2 aviremic individuals displayed elevated IFI27 expression compared with seronegative individuals. Furthermore, in HIV-2 infected individuals, IFI27 expression was also correlated with plasma markers previously linked to inflammation and disease progression in HIV infection. Taken together, our findings suggest that sustained elevation of type I interferon signaling, here reflected by elevated IFI27 expression in the chronic infection phase, is a key pathogenic feature of both HIV-1 and HIV-2.

Альбумінурія та ВІЛ-інфекція в педіатричних пацієнтів

HIV infection increases the risk of developing chronic kidney disease (CKD). Diagnosis at an early stage of HIV associated kidney disease in children is of particular importance, given its prevalence. Determination of the concentration of albumin and creatinine in a single portion of urine, followed by the calculation of the albumin/creatinine ratio (ACR) is used for early diagnosis and assessment of the progression of CKD. Purpose - to study the frequency and risk factors of albuminuria in children with HIV infection, depending on the stage of the disease, immunosuppression, and viral load. Materials and methods. 73 children with HIV infection were examined. Albumin was analyzed in the morning urine sample twice (during the first and third months of observation) using a Beckman Coulter AU 480 series analyzer. Albuminuria was assessed by ACR. The criterion for a moderately elevated level of albuminuria was considered as ACR ≥3 mg/mmol in both measurements and was interpreted as the presence of microalbuminuria (MAU). Results. A steady increase in ACR was noted in 19 (26.0%) patients. The influence of the stage of HIV-infection on the level of albuminuria has not been established. Non-significant immunosuppression (IS) sharply reduced the chances of MAU - OR=0.019 (CI: 0.002-0.159), the presence of a very severe stage of IS significantly increased them - OR=18.89 (CI: 4.33-82.32). There was a pronounced inverse correlation between the ACR and the CD4+ count, both absolute (ρ=-0.51; p<0.001) and relative (ρ=-0.53; p<0.001). It was found that against the background of viral load, the average ACR was twice as high, and the percentage of MAU was nine times higher. In the case of normal viral overload, the chances of moderately elevated albuminuria were significantly reduced - OR=0.048 (CI: 0.012-0.194). The highest rates of ACR were observed in children with a viral load of more than 100,000 copies of RNA/ml, among these patients, MAU was stated in ¾ of cases. A high viral load increased the risks of MAU by one and a half orders of magnitude - OR=15.30 (CI: 3.51-66.68). Elevated ACR was recorded 3.6 times more often in children with progressive HIV-infection than in other patients (OR=14.13; CI: 1.47-136.12; p<0.02). Conclusions. More than a quarter of children with HIV-infection have moderately elevated albuminuria. Renal dysfunction in children with HIV infection has been most closely associated with very severe immunosuppression, RNA HIV viral load >100,000 copies/ml, and progressive course of HIV-infection, as evidenced by albuminuria studies. The study was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was adopted by the Local Ethics Committee of the institution specified in the work. The informed consent of the parents or guardians of the children was obtained for the study. The authors declare no conflict of interest. Key words: HIV infection, children, albuminuria, risk factors.

Ensemble clustering of longitudinal bivariate HIV biomarker profiles to group patients by patterns of disease progression

This paper describes an ensemble cluster analysis of bivariate profiles of HIV biomarkers, viral load and CD4 cell counts, which jointly measure disease progression. Data are from a prevalent cohort of HIV positive participants in a clinical trial of vitamin supplementation in Botswana. These individuals were HIV positive upon enrollment, but with unknown times of infection. To categorize groups of participants based on their patterns of progression of HIV infection using both biomarkers, we combine univariate shape-based cluster results for multiple biomarkers through the use of ensemble clustering methods. We first describe univariate clustering for each of the individual biomarker profiles, and make use of shape-respecting distances for clustering the longitudinal profile data. In our data, profiles are subject to either missing or irregular measurements as well as unobserved initiation times of the process of interest. Shape-respecting distances that can handle such data issues, preserve time-ordering, and identify similar profile shapes are useful in identifying patterns of disease progression from longitudinal biomarker data. However, their performance with regard to clustering differs by severity of the data issues mentioned above. We provide an empirical investigation of shape-respecting distances (Fréchet and dynamic time warping (DTW)) on benchmark shape data, and use DTW in cluster analysis of biomarker profile observations. These reveal a primary group of ‘typical progressors,’ as well as a smaller group that shows relatively rapid progression. We then refine the analysis using ensemble clustering for both markers to obtain a single classification. The information from joint evaluation of the two biomarkers combined with ensemble clustering reveals subgroups of patients not identifiable through univariate analyses; noteworthy subgroups are those that appear to represent recently and chronically infected subsets.

Evaluating the cost-effectiveness of a pre-exposure prophylaxis program for HIV prevention for men who have sex with men in Japan

Men who have sex with men (MSM) have been disproportionally affected by the HIV epidemic in many countries, including Japan. Although pre-exposure prophylaxis (PrEP) is a strong prevention tool, it is not yet approved in Japan. A Markov model was developed to describe HIV infection and disease progression in an MSM cohort (N = 1000) in Japan receiving a PrEP program. The model was used to evaluate the cost-effectiveness of a PrEP program. HIV/AIDS treatment, screening, hospitalization due to AIDS, and PrEP were considered as costs and quality-adjusted life-years (QALYs) gained as utilities. Cost-effectiveness was assessed by comparing the incremental cost-effectiveness ratio (ICER) over a 30-year period against the willingness to pay (WTP) threshold. One-way sensitivity and probabilistic sensitivity analyses were performed. With 50% PrEP coverage, the PrEP program became dominant against the program without PrEP, using a threshold of 5.0 million JPY/QALY (45,455 USD). The probabilistic sensitivity analysis revealed that the PrEP program was dominant or at least cost-effective in most cases of 10,000 simulations. Therefore, preparing cheaper PrEP pills, which results in PrEP being dominant or ICER being lower than the WTP threshold, is important to make the program cost-effective. Introduction of PrEP to an MSM cohort in Japan would be cost-effective over a 30-year time horizon.

Dynamical analysis and optimal control of an age-since infection HIV model at individuals and population levels

To study the impact of HIV infection at the individual level on the transmission of HIV/AIDS at the population level, in this paper, we formulate a multi-scale HIV model coupled with a two stages viral model (lymphoid tissue and blood) and an infection-age structured HIV epidemic model. Then we establish the well-posedness problem, derive the basic reproduction numbers and analyze the stability of equilibria for the coupled model. In order to investigate the effect of giving treatments to individuals on the disease, we further consider an optimal control problem subject to multiple drug treatments for the within-host model. For such control problem, we can obtain the optimal drug administration strategies to minimize the total number of transmissions from an infected individual over the course of infection. Some numerical simulations are presented to investigate the impact of the optimal control quantitatively on the viral load within the host and the between-host transmission dynamics. Our results suggest that controlling the progression of HIV infections at the individuals level is an effective measure to decrease the HIV transmission at the population level.

IFI27 is a potential therapeutic target for HIV infection

Background Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health. Methods Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 and GPL10558 of GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA. Results We obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells. Conclusion The above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.

Opioids Regulate the Immune System: Focusing on Macrophages and Their Organelles.

Opioids are the most widely used analgesics and therefore have often been the focus of pharmacological research. Macrophages are the most plastic cells in the hematopoietic system. They show great functional diversity in various organism tissues and are an important consideration for the study of phagocytosis, cellular immunity, and molecular immunology. The expression of opioid receptors in macrophages indicates that opioid drugs act on macrophages and regulate their functions. This article reviewed the collection of research on effects of opioids on macrophage function. Studies show that opioids, both endogenous and exogenous, can affect the function of macrophages, effecting their proliferation, chemotaxis, transport, phagocytosis, expression of cytokines and chemokine receptors, synthesis and secretion of cytokines, polarization, and apoptosis. Many of these effects are closely associated with mitochondrial function and functions of other organelles in macrophages. Therefore, in depth research into effects of opioids on macrophage organelles may lead to some interesting new discoveries. In view of the important role of macrophages in HIV infection and tumor progression, this review also discusses effects of opioids on macrophages in these two pathological conditions.

People living with HIV/AIDS (PLHAs) Knowledge regarding progression of HIV infection

People living with HIV/AIDS (PLHAs) Knowledge regarding progression of HIV infection

The Difference Of PT, aPTT, Fibrinogen, D-Dimer Activities In HIV Patients With CD4 Count Of <200 uL And >200 uL

ABSTRACT
 Introduction: HIV is a developing disease that has been a global problem. The progress of HIV infection is characterized by decreased CD4 count. Hemostasis disorder is often found in patients with HIV, where the formed virus-antibody complex can activate the coagulation system, beginning from the activation of the Hageman factor (Factor XII) into the active form (Factor XIIa). This factor will activate the fibrinolysis process. Fibrin polymer is broken down into fragments X and Y. Fragment Y is further broken down into Fragment D and E, which is known as D-dimer.
 Objective: To determine the difference of PT, aPTT, Fibrinogen, and D-Dimer in HIV patients with a CD4 lymphocyte count of < 200/µL and > 200/µL in H. Adam Malik General Hospital Medan.
 Hypothesis: There is a difference of PT and aPTT activities in HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL and a difference of D-dimer and fibrinogen levels in HIV patients with a CD4 count of < 200/µL and > 200/µL in H. Adam Malik General Hospital Medan.
 Methods: This study was conducted in the Clinical Pathology Laboratory, Department of Internal Medicine, H. Adam Malik General Hospital. Samples were collected with a consecutive sampling method which included patients diagnosed with HIV in H. Adam Malik General Hospital Medan from September 2019 to July 2020 who fulfilled the inclusion and exclusion criteria. Thirty-eight patients were divided into two groups, i.e., HIV patients with a CD4 count of < 200/µL and HIV patients with a CD4 lymphocyte count of > 200/ µL.
 Results: Mann-Whitney test was used to assess the comparison of PT and aPTT values between HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL. The result was significant with a p-value = 0.002, which means that there is a significant difference in PT and aPTT values between HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL. An Independent T-test was used to assess the difference in fibrinogen level between HIV patients with a CD4 count of < 200/µL and > 200/µL, which resulted in p-value = 0.032. This means that there is a significant difference in fibrinogen levels between HIV patients with a CD4 count of < 200/µL and > 200/µL. Mann-Whitney test was used to determine the comparison in D-dimer level between HIV patients with a CD4 count of < 200/µL and > 200/µL, which showed a p-value = 0.002. This indicated a significant difference in D-dimer level between HIV patients with a CD4 count of < 200/µL and > 200/µL.
 Conclusion: The lower the CD4 lymphocyte count, the higher the activities of PT, aPTT, fibrinogen, and D-dimer in HIV patients.
 
 Keywords: HIV, PT, aPTT, D-Dimer, Fibrinogen, Hemostasis