Neutrophil Expression of T and B Immunomodulatory Molecules in HIV Infection.

Objective: Evaluate the expression of B and T cell immunomodulatory molecules in polymorphonuclear neutrophils (PMN) in HIV-infected patients. Methods: HIV load, bacterial translocation and neutrophils' expression of T [programmed death ligand, interleukin-10+, arginase 1+] and B [BAFF, APRIL] molecules were analyzed in different cohorts and time points: a control group of 25 healthy individuals and two groups of HIV-infected patients. Group 1 of patients included 35 untreated patients, studied at baseline and after antiretroviral therapy (ART). Group 2 was composed of 25 patients with undetectable viral load after a median of 101 months of ART prior to inclusion in the study. Results: Compared with the control group, group 1 patients showed increased bacterial translocation and their PMN had a significantly higher expression of T and B-cell immunomodulatory molecules, both at baseline and after 12 months of ART. Group 2 patients showed reduced bacterial translocation levels when compared with group 1 patients after 12 months of treatment. PMN expression of B-cell modulators was similar between group 2 patients and healthy controls, although the expression of T-cell modulators remained increased. Conclusion: In HIV-infected patients, the expression of B-cell stimulatory and T-cell suppressive molecules by neutrophils was increased at baseline and after a limited time of therapy. After a prolonged period of ART, only PMNs expression of T-cell immunosuppressive molecules remained elevated.

HIV antibodies level as a marker of HIV persistence: the role of hepatitis C virus coinfection.

Human immunodeficiency virus (HIV) antibodies have been proposed as a measure of the size of the HIV reservoir. The aim of our study is to quantify the anti-HIV antibodies level in a cohort of people living with HIV (PLWH), stratified based on the presence of continuous undetectable HIV viral load and the co-existence of hepatitis C virus infection. A sample of 229 HIV-monoinfected (n = 114) or HIV/HCV-coinfected [either with resolved HCV infection (n = 75) or active HCV coinfection (n = 40)] patients, followed up a median of 34 (IQR 20-44) months, was studied. Anti-HIV index was obtained as the 1:800 dilution of HIV antibodies. CD4+ T cell count, time with undetectable HIV viral load, annual increase of CD4+ T cell count, anti-HCV therapy, and diagnosis of cirrhosis were analyzed. Patients with a continued suppressed HIV viral load had significant lower anti-HIV index compared with those with virologic failure during the follow-up. Significant higher CD4+ T cell increase was observed in those with a lower anti-HIV index. HIV-monoinfected patients showed an anti-HIV index significantly lower than patients with HCV coinfection. Resolved HCV infection after interferon-based therapy, but not with direct acting antivirals, was associated with a lower anti-HIV index. HIV/HCV-coinfected patients showed higher HIV antibodies level when compared with HIV-monoinfected individuals. A decrease in anti-HIV index in HIV/HCV-coinfected patients was detected when a sustained virological HCV response was obtained after interferon-based therapy, in possible relation with the direct or indirect effect of interferon on PLWH CD4 T cells.

Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients.

This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIV-infected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load -10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin -IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals.

Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity.

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

[Use of an empirical antiretroviral treatment depends on the primary resistance rate of the human immunodeficiency virus]. / La práctica de un tratamiento antirretroviral empírico es dependiente del porcentaje de resistencias primarias del virus de la inmunodeficiencia humana.

OBJECTIVE: The objective of this study was the analysis of the prevalence and type of primary resistance to antiretroviral drugs in patients diagnosed with HIV infection, and to determine the most appropriate empirical treatment to obtain a virological and immunological response. PATIENTS AND METHODS: An observational analysis of patients with a de novo diagnosis of HIV infection during the period 2008-2010. Clinical, immunological and virological characteristics, including genotype analysis of resistance to antiretrovirals, were considered as independent variables. The dependent variable was an undetectable HIV viral load after six months of treatment. Data are provided as median (interquartile range) and absolute number (percentage). RESULTS: Seventy-three patients with a de novo diagnosis of HIV infection were included [53 males (73%); 36 (30-46) years-old; prior use of intravenous drugs: 5 patients (7%); hepatitis C virus co-infection: 13 individuals (18%)]. Ten patients (14%) showed symptoms attributable to acute HIV infection. A CD4+ T cell count lower than 350 mm(3) was detected in a 37% (n=27) of all patients. The initiation of antiretroviral therapy followed the GESIDA recommendations (no therapy: 20 patients; tenofovir+emtricitabine+efavirenz: 28 patients; abacavir+lamivudine+efavirenz: 1 patient; tenofovir+emtricitabine+protease inhibitors: 5 patients; abacavir+lamivudine+protease inhibitors: 1 patient; 18 patients were lost in the follow-up). After starting antiretroviral therapy, the resistance analyses detected the existence of primary resistance to antiretrovirals in 12.7% (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in 9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%; there were no cases of resistance to protease inhibitors. Consequently, antiretroviral therapy was changed in 5 (14%) out of 35 patients, attaining an undetectable HIV viral load at 6 months in all of them. The primary resistance to antiretrovirals was not related with epidemiological, virological (including infection by non B subtype) or immunological variables. CONCLUSIONS: In the present study, a change in the epidemiological pattern of de novo diagnosis of HIV infection in our area has been observed. The existence of resistance mutations in more than 5% of the new cases is noteworthy. This finding must be considered in order to establish the rules of empirical treatment in our area.

[Erythrovirus B19 infection]. / Infección por Erythrovirus B19.

Erythrovirus B19 has been associated with an expanding range of clinical disorders since its identification as the etiological agent of erythema infectiosum, or fifth disease of childhood: acute arthropathy, dermatologic manifestations, chronic anemia in immunocompromised patients, and transient aplastic crisis in individuals with underlying chronic hemolytic disorders. Furthermore, exposure to and infection by B19 virus can lead to serious complications during pregnancy, which may result in fetal anemia, spontaneous abortion, and hydrops fetalis. Consequently, the B19 immune status of pregnant women should be routinely determined. Because many immunocompromised patients with chronic anemia will respond positively to intravenous immunoglobulin therapy, laboratory confirmation of B19 infection is required. Since Erythrovirus B19 cannot be routinely grown in vitro, diagnostic methods for detecting the presence of B19 by molecular techniques or by investigating the specific immune response should be considered in clinical microbiology laboratories.

Infección por Erythrovirus B19 / Erythrovirus B19 infection

Erythrovirus B19 se ha asociado con una gran variedad de manifestaciones clínicas diferentes desde que se descubriera como agente etiológico del eritema infeccioso o quinta enfermedad infantil: artropatía aguda, manifestaciones dermatológicas diversas, anemia crónica en inmunodeprimidos y crisis aplásica transitoria, en pacientes con anemias hemolíticas crónicas. Además, la exposición y la infección por B19 durante el embarazo pueden acarrear graves complicaciones para el feto, como anemia fetal, aborto espontáneo e hydrops fetalis. Por tanto, el estado inmunitario frente al B19 debería realizarse de forma sistemática en la embarazada. Muchos pacientes inmunodeprimidos con anemia crónica responden al tratamiento con inmunoglobulina por vía intravenosa; por ello, en estos casos es de gran importancia la confirmación de la infección por el virus. Puesto que es muy difícil su cultivo in vitro, consideramos que actualmente los laboratorios de microbiología clínica deberían realizar las técnicas serológicas y los nuevos métodos de detección de ADN viral disponibles para el diagnóstico de la infección por B19

Erythrovirus B19 has been associated with an expanding range of clinical disorders since its identification as the etiological agent of erythema infectiosum, or fifth disease of childhood: acute arthropathy, dermatologic manifestations, chronic anemia in immunocompromised patients, and transient aplastic crisis in individuals with underlying chronic hemolytic disorders. Furthermore, exposure to and infection by B19 virus can lead to serious complications during pregnancy, which may result in fetal anemia, spontaneous abortion, and hydrops fetalis. Consequently, the B19 immune status of pregnant women should be routinely determined. Because many immunocompromised patients with chronic anemia will respond positively to intravenous immunoglobulin therapy, laboratory confirmation of B19 infection is required. Since Erythrovirus B19 cannot be routinely grown in vitro, diagnostic methods for detecting the presence of B19 by molecular techniques or by investigating the specific immune response should be considered in clinical microbiology laboratories