Bystander Effects and Profibrotic Interactions in Hepatic Stellate Cells during HIV and HCV Coinfection.

This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells' susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-ß, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.

Sarcopenia Related to Human Immunodeficiency Virus: Protective Effects of Exercise.

We discuss recent evidence supporting the hypothesis that sarcopenia is an emerging health concern among people with human immunodeficiency virus (HIV) because of increasing life expectancy and HIV- and treatment-related comorbidities. We also hypothesize that combined exercise at higher intensity has a key role in managing sarcopenia in this population because it directly (increases muscle strength and stimulates hypertrophy) and indirectly (prevents mitochondrial dysfunction, oxidative stress, and persistent inflammation) counteracts sarcopenia hallmarks.

Hemostasis in elderly patients with human immunodeficiency virus (HIV) infection-Cross-sectional study.

INTRODUCTION: Aging and chronic HIV infection are clinical conditions that share the states of inflammation and hypercoagulability. The life expectancy of the world population has increased in the last decades, bringing as complications the occurrence of diseases that undergoing metabolic, bone, cardiological, vascular and neurological alterations. HIV-infected patients experience these changes early and are living longer due to the success of antiretroviral therapy. The objectives of this study was to evaluate some changes in the plasma hemostatic profile of 115 HIV-reactive elderly individuals over 60 years old in the chronic phase of infection, and compare with 88 healthy uninfected elderly individuals. Plasma determinations of D-dimers, Fibrinogen, von Willebrand Factor, Antithrombin, Prothrombin Time, Activated Partial Thromboplastin Time, and platelet count were performed. In the HIV-reactive group, these variables were analyzed according to viral load, protease inhibitor use and CD4+ T lymphocyte values. After adjusted values for age and sex, the results showed higher levels of Antithrombin (103%; 88%, p = 0.0001) and Prothrombin Time activities (92.4%; 88.2%, p = 0.019) in the HIV group compared to the control group. We observed higher values of Fibrinogen in protease inhibitor users in both the male (p = 0.043) and female (p = 0.004) groups, and in the female HIV group with detected viral load (p = 0.015). The male HIV group with a CD4+ count> 400 cells / mm3 presented higher von Willebrand Factor values (p = 0.036). D-Dimers had higher values in the older age groups (p = 0.003; p = 0.042, respectively). CONCLUSION: Our results suggest that the elderly with chronic HIV infection with few comorbidities had a better hemostatic profile than negative control group, reflecting the success of treatment. Protease inhibitor use and age punctually altered this profile.

Case Report: Hemophagocytic Lymphohistiocytosis Caused by Disseminated Histoplasmosis in a Venezuelan Patient with HIV and Epstein-Barr Virus Reactivation Who Traveled to Japan.

We describe a Venezuelan visitor to Japan who was diagnosed with hemophagocytic lymphohistiocytosis (HLH). The patient was also diagnosed with human immunodeficiency virus (HIV) and Epstein-Barr virus infection by the Western blot and polymerase chain reaction (PCR) tests, respectively. The cause of HLH was considered to be these two infections at first; however, the patient did not recover with antiretroviral/anti-herpes virus therapy. Thereafter, diagnosis of disseminated histoplasmosis was confirmed with an antigen detection test, culture, and PCR test of blood, urine, and bone marrow, and the patient improved gradually after the initiation of liposomal amphotericin B. This case highlights the importance of ruling out endemic mycosis as a cause of HLH even if other probable causes exist in patients from endemic areas.

Fostemsavir: a new CD4 attachment inhibitor.

PURPOSE OF REVIEW: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. RECENT FINDINGS: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds. A phase 3 study showed a reduction in plasma viral RNA of 1.21-1.73 log10 copies/ml from baseline after 8 days of functional monotherapy; at 48 weeks, up to 82% of patients treated with FTR and an optimized background ARV regimen achieved virological suppression below 50 copies/ml. SUMMARY: FTR is an investigational HIV drug with a novel mechanism of action that demonstrates virologic activity in HIV-infected treatment-experienced individuals.

Growth scaling for the early dynamics of HIV/AIDS epidemics in Brazil and the influence of socio-demographic factors.

The early dynamics of an infectious disease outbreak can be affected by various factors including the transmission mode of the disease and host-specific factors. While recent works have highlighted the presence of sub-exponential growth patterns during the early phase of epidemics, empirical studies examining the contribution of different factors to early epidemic growth dynamics are lacking. Here we aim to characterize and explain the early incidence growth patterns of local HIV/AIDS epidemics in Brazil as a function of socio-demographic factors. For this purpose, we accessed annual AIDS incidence series and state-level socio-demographic variables from publicly available databases. To characterize the early growth dynamics of the HIV/AIDS epidemic, we employed the generalized-growth model to estimate with quantified uncertainty the scaling of growth parameter (p) which captures growth patterns ranging from constant incidence (p=0) to sub-exponential (0 < p < 1) and exponential growth dynamics (p=1) at three spatial scales: national, regional, and state levels. We evaluated the relationship between socio-demographic variables and epidemic growth patterns across 27 Brazilian states using mixed-effect regression analyses. We found wide variation in the early dynamics of the AIDS epidemic in Brazil, displaying sub-exponential growth patterns with the p parameter estimated substantially below 1.0. The mean p was estimated to be 0.81 at the national level, with a range of 0.72-0.85 at the regional level, and a range of 0.28-0.96 at the state level. Our findings support the notion that socio-demographic factors contribute to shaping the early growth dynamics of the epidemic at the local level. Gini index and socio-demographic index were negatively associated with the parameter p, whereas urbanicity was positively associated with p. The results could have theoretical significance in understanding differences in growth scaling across different sexually transmitted disease systems, and have public health implications to guide control.

HIV-associated opsoclonus-myoclonus-ataxia syndrome: early infection, immune reconstitution syndrome or secondary to other diseases? Case report and literature review.

Opsoclonus-myoclonus-ataxia (OMA) syndrome is a debilitating autoimmune neurological disorder. Post-infectious opsoclonus-myoclonus-ataxia syndrome has been described with varying bacterial, spirochetal, and viral infections including several patients with HIV. However, specific immunopathological mechanisms that may lead to opsoclonus-myoclonus in HIV-positive patients are unknown.We report a case of HIV-associated opsoclonus-myoclonus and early HIV infection. A review of published literature shows opsoclonus-myoclonus can occur during early infection, in immune reconstitution syndrome or in association with other infections, especially tuberculosis.

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi.

The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV), the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.

Knee extension and flexion strength asymmetry in Human Immunodeficiency Virus positive subjects: a cross-sectional study.

BACKGROUND: Human Immunodeficiency Virus positive subjects present impairment in muscle function, neural activation, balance, and gait. In other populations, all of these factors have been associated with muscle strength asymmetry. OBJECTIVE: To investigate the existence of muscle strength asymmetry between dominant and non-dominant lower limbs and to determine the hamstrings-to-quadriceps strength ratio in Human Immunodeficiency Virus positive subjects. METHODS: In this cross-sectional study, 48 subjects were included (22 men and 26 women; mean age 44.6 years), all of them under highly active antiretroviral therapy. They performed isokinetic strength efforts at speeds of 60°/s and 180°/s for knee extension and flexion in concentric-concentric mode. RESULTS: Peak torque was higher (p<0.01) at 60°/s for quadriceps (193, SD=57 vs. 173, SD=55% body mass) and hamstrings (97, SD=36 vs. 90, SD=37% body mass) in dominant compared to non-dominant. Similarly, peak torque was higher at 180°/s (quadriceps 128, SD=44 vs. 112, SD=42; hamstrings 64, SD=24 vs. 57, SD=26% body mass) in dominant. Average power was also higher for all muscle groups and speeds, comparing dominant with non-dominant. The hamstrings-to-quadriceps ratio at 60°/s was 0.50 for dominant and 0.52 for non-dominant, and at 180°/s, it was 0.51 for both limbs, with no significant difference between them. The percentage of subjects with strength asymmetry ranged from 46 to 58%, depending upon muscle group and speed analyzed. CONCLUSION: Human Immunodeficiency Virus positive subjects present muscle strength asymmetry between lower limbs, assessed through isokinetic dynamometry.

The emergence and evolution of the research fronts in HIV/AIDS research.

In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", "HIV-1" and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics. Thirteen research fronts were identified in this sub-network. The biggest and oldest front is related to the clinical knowledge on the disease in the patient. Nine of the fronts are related to the study of specific molecular structures and mechanisms and two of these fronts are related to the development of drugs. The rest of the fronts are related to the study of the disease at the cellular level. Interestingly, the emergence of these fronts occurred in successive "waves" over the time which suggest a transition in the paradigmatic focus. The emergence and evolution of the biomedical fronts in HIV/AIDS research is explained not just by the partition of the problem in elements and interactions leading to increasingly specialized communities, but also by changes in the technological context of this health problem and the dramatic changes in the epidemiological reality of HIV/AIDS that occurred between 1993 and 1995.

Zika Virus Infection Associated With Congenital Birth Defects in a HIV-infected Pregnant Woman.

We describe a case of Zika virus infection acquired during the first trimester in a HIV-infected pregnant woman that led to multiple fetal malformations and fetal demise in Rio de Janeiro, Brazil.

Anal canal squamous carcinoma / Carcinoma epidermóide do canal anal

ABSTRACT Background: Anal canal carcinoma is a rare neoplasm, representing 2% of the digestive tumors, and the most common is squamous cell carcinoma, with an increasing incidence. Objective: The study aims to elucidate the pathogenesis of an increasingly prevalent disease, as well as to update treatment and prognosis. Methods: A literature search in Pubmed database, including articles from 2005 to 2015 and cross-research articles with the initial research. Results: Several studies prove the role of HPV as a major risk factor in the development of squamous cell carcinoma of anal canal, as well as a greater prevalence of this neoplasia in HIV-positive people and in those who practice receptive anal intercourse. In the last two decades chemoradiotherapy remains the treatment of choice, and abdominoperineal resection is reserved for those cases of treatment failure or recurrence. Evidence advances in order to adapt the treatment to each patient, taking into account individual prognostic factors and biological tumor characteristics. Conclusions: Squamous cell carcinoma of the anal canal is a neoplasm associated with HPV; therefore, screening and vaccination programs of male individuals, by way of prevention, should be started. Many studies are needed in order to achieve development in the treatment as well as in the evaluation of the biological characteristics of the tumor.

RESUMO Introdução: O carcinoma do canal anal é uma neoplasia rara, representando 2% dos tumores digestivos, sendo o epidermóide o mais comum com uma incidência crescente. Objetivo: Este estudo pretende elucidar sobre a etiopatogenia desta patologia cada vez mais prevalente, assim como atualizar sobre o tratamento e prognóstico. Métodos: Pesquisa bibliográfica na base de dados Pubmed, incluindo artigos de 2005 a 2015, assim como artigos de pesquisa cruzada com os artigos iniciais. Resultados: Diversos estudos provam o papel do HPV como um fator de risco major no desenvolvimento de carcinoma epidermóide do canal, assim como uma maior prevalência desta neoplasia na população HIV positiva e nos que praticam sexo anal recetivo. O tratamento continua a ser desde há duas décadas a quimioradioterapia, reservando a resseção abdominoperineal para casos de falência do tratamento ou recorrência. A evidência avança no sentido de adequar o tratamento a cada doente, tendo em conta fatores prognósticos individuais e as características biológicas do tumor. Conclusões: O carcinoma epidermóide do canal anal é uma neoplasia associada ao HPV, logo deveria iniciar-se programas de rastreio e vacinar o sexo masculino como prevenção. Muitos estudos são necessários para evoluir no tratamento, assim como na avaliação das características biológicas do tumor.

Human platelets antigens influence the viral load of platelets after the interaction of the platelets with HCV and HIV in vitro.

INTRODUCTION: In this study, we evaluated hepatitis C virus (HCV) and human immunodeficiency virus (HIV) - platelet interactions in vitro as well as human platelets antigen (HPA) polymorphisms. METHODS: Platelets were obtained from 100 healthy HPA-genotyped volunteer donors and incubated with HIV or HCV. The viral load after in vitro exposure was detected. RESULTS: The viral load in the platelets after exposure to the virus was higher in the HIV exposure than in the HCV exposure. CONCLUSIONS: HIV-platelet ligation could be more efficient than HCV-platelet interaction. Further, the HPA-1b allele seems to influence the interaction of platelets with HCV.

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome.

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.

Particular activation phenotype of T cells expressing HLA-DR but not CD38 in GALT from HIV-controllers is associated with immune regulation and delayed progression to AIDS.

The spontaneous control of HIV replication in HIV-controllers underlines the importance of these subjects for exploring factors related to delayed progression. Several studies have revealed fewer immune alterations and effector mechanisms related to viral control, mainly in peripheral blood, in these individuals compared to normal progressors. However, immune characterization of gut-associated lymphoid tissue (GALT), the major target of infection, has not been thoroughly explored in these subjects. We evaluated the following parameters in GALT samples from 11 HIV-controllers and 15 HIV-progressors: (i) frequency and activation phenotype of T cells; (ii) expression of transcription factors associated with immune response profiles; and (iii) frequency of apoptotic cells. Interestingly, HIV-controllers exhibited a particular activation phenotype, with predominance of T cells expressing HLA-DR but not CD38 in GALT. This phenotype, previously associated with better control of infection, was correlated with low viral load and higher CD4(+) T cell count. Furthermore, a positive correlation of this activation phenotype with higher expression of Foxp3 and RORγT transcription factors suggested a key role for Treg and Th17 cells in the control of the immune activation and in the maintenance of gut mucosal integrity. Although we evaluated apoptosis by measuring expression of cleaved caspase-3 in GALT, we did not find differences between HIV-controllers and HIV-progressors. Taken together, our findings suggest that predominance of HLA-DR(+) T cells, along with lower immune activation and higher expression of transcription factors required for the development of Treg and Th17 cells, is associated with better viral control and delayed progression to AIDS.

Comportamiento de infecciones cérvico-vaginales y alteraciones citocolposcópicas en mujeres infectadas con VIH/sida / Behavior of cervical-vaginal infections taking into account colposcopy and changes in women infected with HIV/AIDS

Se realizó un estudio donde se estudiaron 33 pacientes, de sexo femenino portadoras de VIH/sida atendidas en las consultas de patología de cuello del Hospital Ginecobstétrico provincial Ana Betancourt de Mora y del Policlínico Principal de urgencias Ignacio Agramonte, Camagüey, en el período comprendido entre abril del 2011 y mayo de 2012. El 24,3 por ciento de las mujeres en estudio padecieron vaginosis bacteriana. Las citologías fueron negativas de células neoplásicas en el 96,97 por ciento, en cambio se encontró que el 9,09 por ciento de las féminas(AU)

An observational study is done in 33 patients of females with HIV / AIDS that were treated in neck pathology consultations at the Gynecobstetric provincial Hospital Ana Betancourt de Mora and the Main Polyclinic Ignacio Agramonte from April 2011 to May 2012. The 24,3 percent of women in the study suffered from bacterial vaginosis. The cytology was negative for neoplastic cells in the 96,97 percent ; however it was found that 9,09 per centet of females showed high-grade lesions in colposcopy and 6,06 percentt low grade lesions. 35, 2 percent of the women with positive microbiological diagnosis and those who had abnormal colposcopy showed lymphocyte numbers below 500 cell/mm³

Continuous neural identifier for uncertain nonlinear systems with time delays in the input signal.

Time-delay systems have been successfully used to represent the complexity of some dynamic systems. Time-delay is often used for modeling many real systems. Among others, biological and chemical plants have been described using time-delay terms with better results than those models that have not consider them. However, getting those models represented a challenge and sometimes the results were not so satisfactory. Non-parametric modeling offered an alternative to obtain suitable and usable models. Continuous neural networks (CNN) have been considered as a real alternative to provide models over uncertain non-parametric systems. This article introduces the design of a specific class of non-parametric model for uncertain time-delay system based on CNN considering the so-called delayed learning laws analysis. The convergence analysis as well as the learning laws were produced by means of a Lyapunov-Krasovskii functional. Three examples were developed to demonstrate the effectiveness of the modeling process forced by the identifier proposed in this study. The first example was a simple nonlinear model used as benchmark example. The second example regarded the human immunodeficiency virus dynamic behavior is used to show the performance of the suggested non-parametric identifier based on CNN for no fictitious neither academic models. Finally, a third example describing the evolution of hepatitis B virus served to test the identifier presented in this study and was also useful to provide evidence of its superior performance against a non-delayed identifier based on CNN.

Spontaneous control of HIV replication, but not HAART-induced viral suppression, is associated with lower activation of immune cells.

HIV replication control is important to reduce AIDS progression. We determined frequency and activation status of immune cells in spontaneous HIV controllers vs. individuals with highly active antiretroviral therapy (HAART)-controlled viral load. HIV controllers exhibited significantly higher frequency of CD4 T cells and myeloid dendritic cells compared with HAART-controlled viral load. Additionally, HIV controllers have a significantly lower percentage of cells expressing activation markers on CD4 and CD8 T cells, myeloid dendritic cells, and natural killer cells. These findings suggest that during HIV infection, conservation of a normal frequency and physiological range of immune activation is associated with spontaneous, but not HAART-induced, control of viral replication.