HTLV infection in HCV-antibody positive patients in Spain.

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis (TSP) or adult T-cell leukemia (ATL) at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers. The presence of anti-HTLV antibodies was examined in 3,838 consecutive individuals with reactive HCV serology attended during the last three years at 13 hospitals distributed across the Spanish geography. Overall 71% were male and the median age was 41-years old. Foreigners represented 9% of the study population. A total of 50 individuals (1.3%) were seroreactive for HTLV, being 30 confirmed as HTLV-2 and two as HTLV-1 (0.12%). The remaining 18 had indeterminate Western blot patterns. Most individuals with HTLV-2 and HTLV indeterminate serology were HIV-positive, former injection drug users and native Spaniards. In contrast, the two HTLV-1 infections were found in men coming from Brazil and the Dominican Republic, respectively. In summary, the overall prevalence of HTLV infection in individuals living in Spain seropositive for HCV is 1.3%, more than 10-fold greater than in general outclinics in Spain. However, immigrants from HTLV-1 endemic regions and former injection drug users with HTLV-2 infection are by far the major contributory groups in HCV patients. Therefore, testing for HTLV in newly diagnosed HCV individuals would not contribute much to improve late HTLV diagnosis in Spain.

HIV-2 and HTLV-1 infections in Spain, a non-endemic region.

The annual workshop of the Spanish HIV­2/HTLV Study Group was held at the Instituto de Salud Carlos III in Madrid on December 11, 2013. Nearly 100 experts and researchers in retroviruses other than HIV­1, the classical AIDS agent, convened for a one­day meeting devoted to updating knowledge on the epidemiology of HIV­2 and HTLV-1 infections and discussing new diagnostic and therapeutic strategies, with special attention to non­endemic regions such as Spain. The Group was funded 25 years ago and since then has been responsible for the national registry of cases, recording all relevant information for each subject and inviting them to enroll in a prospective cohort and biobank. Up to the end of 2013, a total of 297 individuals with HIV­2 infection were reported in Spain. All but 10 carry HIV­2 subtype A, with the rest being infected with subtype B. Overall, 71% came from sub­Saharan Africa. During the last decade, the incidence of new HIV­2 infections in Spain has remained fairly stable with around 20 cases per year. At the time of diagnosis, plasma HIV­2 RNA was undetectable in 61% of individuals and values in viremic subjects tended to be low (2.8 logs on average). To date, only 26% of HIV­2 individuals have been treated with antiretrovirals. The CD4 counts, however, only increased above 200 cells/mm³ in 42% of them. On the other hand, 74% of non­treated HIV­2 individuals have > 500 CD4+ T­cells/mm³. As in HIV­1 infection, X4 tropism in HIV­2 is associated with lower CD4 counts. A total of 253 individuals with HTLV-1 infection were reported in Spain by the end of 2013. Overall, 58% came from Latin America. HTLV-1­associated myelopathy was diagnosed in 29 patients and adult T­cell leukemia/lymphoma in 18. The highest incidence occurred in 2013, with 34 new HTLV-1 diagnoses, largely as result of expanding HTLV screening in blood banks. Attempts to reduce HTLV-1 proviral load in symptomatic or asymptomatic patients with elevated HTLV-1 DNA using antiretrovirals have produced poor results, although integrase inhibitors could be more successful. Although no cases of HTLV­3 or ­4 have been identified so far in Spain, 769 individuals have been diagnosed with HTLV­2 infection. Up to 85% of the latest cases are coinfected with HIV­1 and are former intravenous drug users.

Molecular epidemiology and clinical features of human T cell lymphotropic virus type 1 infection in Spain.

Human T cell lymphotropic virus type 1 (HTLV-1) infection in Spain is rare and mainly affects immigrants from endemic regions and native Spaniards with a prior history of sexual intercourse with persons from endemic countries. Herein, we report the main clinical and virological features of cases reported in Spain. All individuals with HTLV-1 infection recorded at the national registry since 1989 were examined. Phylogenetic analysis was performed based on the long terminal repeat (LTR) region. A total of 229 HTLV-1 cases had been reported up to December 2012. The mean age was 41 years old and 61% were female. Their country of origin was Latin America in 59%, Africa in 15%, and Spain in 20%. Transmission had occurred following sexual contact in 41%, parenteral exposure in 12%, and vertically in 9%. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was diagnosed in 27 cases and adult T cell leukemia/lymphoma (ATLL) in 17 subjects. HTLV-1 subtype could be obtained for 45 patients; all but one belonged to the Cosmopolitan subtype a. One Nigerian pregnant woman harbored HTLV-1 subtype b. Within the Cosmopolitan subtype a, two individuals (from Bolivia and Peru, respectively) belonged to the Japanese subgroup B, another two (from Senegal and Mauritania) to the North African subgroup D, and 39 to the Transcontinental subgroup A. Of note, one divergent HTLV-1 strain from an Ethiopian branched off from all five known Cosmopolitan subtype 1a subgroups. Divergent HTLV-1 strains have been introduced and currently circulate in Spain. The relatively large proportion of symptomatic cases (19%) suggests that HTLV-1 infection is underdiagnosed in Spain.

Association between HLA alleles and HAM/TSP in individuals infected with HTLV-1.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develops in less than 5 % of HTLV-1 carriers. It is unclear which factors trigger the development of disease. The aim of this study was to explore the influence of HLA alleles on the development of HAM/TSP. A total of 40 HTLV-1-infected individuals belonging to the Spanish HTLV-1 cohort were examined. HTLV-1 proviral load was measured by real-time polymerase chain reaction. HLA class I (A, B, C) and class II (DRB1, DQB1) alleles were genotyped using the bead array technology. Median HTLV-1 proviral load in 12 HAM/TSP patients was greater than in 28 asymptomatic carriers (637 vs. 71 copies per 10(4) peripheral blood mononuclear cells; p = 0.006). Moreover, HAM/TSP was significantly associated with HLA-B 07 and HLA-DRB1 01:01 (p = 0.039). Interestingly, individuals with these HLA alleles had greater HTLV-1 proviral load than asymptomatic carriers (p = 0.036). In summary, HLA testing should be considered in asymptomatic HTLV-1 individuals and close monitoring of HTLV-1 proviral load along with periodic neurological evaluations should be prioritized in HLA-DRB1 01:01 and HLA-B 07 carriers.

Interleukin 28B rs12979860 (CT/TT) genotype is associated with milder hepatic damage in the natural evolution of HCV/HIV coinfection.

Hepatitis C virus (HCV)/human immunodefficiency virus (HIV) coinfection is a major health problem, affecting mostly to individuals with exposure to blood products, as hemophiliacs or intravenous drug users, or those exposed to high-risk sexual practices. Genotyping of interleukin 28B (IL-28B) rs12979860 polymorphism is a useful tool for guiding therapeutic decisions in this disease. On the contrary, there is not enough information on the pathogenic role of this polymorphism in the natural history of the disease. The objective of this study is to describe the relationships between the CT/TT genotype of this polymorphism with viral loads and also with a number of biomarkers of liver function in coinfected patients naïve for treatment for HCV. Seventy-five HCV/HIV coinfected patients were retrospectively recruited in our Hospital from 2010 to 2011. Logistic regression analysis adjusting by [Age], [Sex], [HCV viral genotype], [HCV viral load], [HIV viral load], and [CD4 T cells levels] revealed the IL-28B rs12979860 (CT/TT) genotype as a protective factor against alanine aminotransferase (ALT) levels (>100 IU/L), aspartate aminotransferase (AST) levels (>75 IU/L), and AST-to-platelet ratio index (APRI) score for liver fibrosis (>1.5) [OR, (95% CI), p]: ALT [0.026 (0.001-0.576) 0.021]; AST [0.001 (0.000-0.297) 0.019]; APRI [0.031 (0.002-0.41) 0.008]. Stepwise regression analysis considering the same adjusting variables showed the same results. In consequence, the IL-28B rs12979860 (CT/TT) genotype, which is a marker of poor response to HCV treatment, could be mediating on the contrary a certain protective effect against the hepatic damage caused by this virus in patients coinfected by HIV.

Viral infection is associated with an increased proinflammatory response in chronic obstructive pulmonary disease.

The development of new diagnostic methods based on molecular biology has led to evidence of the important role of respiratory viruses in chronic obstructive pulmonary disease (COPD) exacerbations. Cytokines and chemokines are recognized as key actors in the pathogenesis of COPD. The objective of this study was to evaluate the association between viral infection and host cytokine responses in 57 COPD patients hospitalized with an acute exacerbation. Seventeen cytokines were profiled using a Luminex-Biorad multiplex assay in plasma samples collected in the first 24 h following hospital admission. Stepwise linear regression analysis was performed, taking into account the influence of seven potential confounding factors in the results. Twenty-four out of 57 showed radiological signs of community-acquired pneumonia (CAP) at hospital admission, 25 patients required admission to the intensive care unit (ICU), 20 had a bacterial infection, and 20 showed a detectable respiratory virus in pharyngeal swabs. Regression analysis showed that viral infection correlated with higher levels of interleukin-6 (IL-6) (log value of the coefficient of regression B, p=0.47, 0.044), and monocyte chemoattractant protein-1 (MCP-1) (p=0.43, 0.019), and increased admission to the ICU. Viral infection also correlated with higher levels of interferon-γ (IFN-γ) (p=0.70, 0.026), which, in turn, was inversely associated with the severity of illness. Finally, viral infection was independently associated with higher levels of tumor necrosis factor-α (TNF-α) (p=0.40, 0.002). Thus our study demonstrates that in patients with COPD exacerbations, viral infection is directly associated with higher systemic levels of cytokines central to the development of the antiviral response, which are also known to contribute to inflammation-mediated tissue damage. These results reveal a potential specific role of viral infection in the pathogenesis of COPD exacerbations.

Prevalence of HTLV-1/2 infections in Spain: A cross-sectional hospital-based survey.

The presence of antibodies to human T-lymphotropic virus (HTLV) types 1 and 2 was examined in 5742 sera belonging to consecutive adult outpatients attended during June 2008 at 13 different hospitals across Spain. Overall, 58.8% were female. Foreigners represented 8% of the study population. Seven individuals were seropositive for HTLV-2 (overall prevalence 0.12%). No cases of HTLV-1 infection were found. All HTLV-2(+) subjects were Spanish natives, of whom six were coinfected with HIV-1 and five with hepatitis C virus (HCV). Moreover, all but one of the HTLV-2(+) subjects had been intravenous drug users. In summary, this cross-sectional survey suggests that the rate of HTLV infection in Spain is low, and is mostly represented by HTLV-2. Infected individuals are generally Spanish natives with a prior history of intravenous drug use and are coinfected with HIV-1 and/or HCV.

Seroprevalence of HTLV-1/2 infection among native and immigrant pregnant women in Spain.

HTLV-1=2 antenatal screening is not mandatory in European countries. The rapid increase in immigrants coming from areas endemic for HTLV-1 infection has compelled a review of this policy in Spain. From February 2006 to December 2007, a cross-sectional study was carried out in all pregnant women attended at 10 different Spanish hospitals. An enzyme immunoassay (EIA) was used to test serum HTLV-1=2 antibodies; reactive samples were further confirmed by Western blot and=or polymerase chain reaction. A total of 20,518 pregnant women were examined, of whom 18,266 (89%) were native Spaniards. Overall, 946 (4.6%) of the immigrants came from HTLV-1 endemic areas (mainly Central and South America and sub-Saharan Africa). Four samples were EIA seroreactive for HTLV-1=2, two of them in women infected with HTLV-1 coming from endemic areas. The other two women were infected with HTLV-2; one was an immigrant from Bolivia and another was a native Spaniard who admitted prior injection drug use and was HIV-1 positive. The overall HTLV-1=2 seroprevalence was 0.19 per 1000 (95% CI: 0.05-0.49=1000). For HTLV-1, the seroprevalence was 2.11 per 1000 (95% CI: 0.26-7.62=1000) in pregnant women from endemic areas. The seroprevalence of HTLV-1=2 infection is below 0.02% among pregnant women in Spain, and therefore universal screening for HTLV-1=2 infection in antenatal clinics is not warranted. However, HTLV-1=2 screening could be considered in pregnant women coming from endemic areas, in whom the rate of infection is nearly 1000-fold higher than in native Spaniards and are the only group infected with the more pathogenic HTLV-1.

[Microbiological diagnosis of HIV infection]. / Diagnóstico microbiológico de la infección por el VIH.

Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

[Genotypic resistence in patients infected with HIV and its correlation with therapy]. / Resistencias genotípicas en pacientes con infección por el virus de la inmunodeficiencia humana. Correlación con las pautas terapéuticas empleadas en su tratamiento.

BACKGROUND AND OBJECTIVE: Our goal was to establish the different therapeutic regimens used in our clinical setting, and to determine the prevalence of genotypic resistances in patients under antiretroviral therapy, analyzing the relationship between the appearance of mutations and treatments along with other HIV related variables. MATERIAL AND METHOD: 191 samples from the same number of patients who were on antiretroviral therapy and virological failure were analyzed. Samples were processed by means of the genotypic technique LiPA in order to study the presence of mutations in the reverse transcriptase (RT) and the protease (P) genes. Prescribed therapeutic regimens and epidemiological variables relevant in HIV infection were also analyzed. RESULTS: Overall resistance prevalence was 72.32%. By LiPA, RT mutations were detected in 71.43% of patients, being M184V, T215Y and L41M the most frequent ones. Moreover, P mutations were detected in 59.38% of cases, being V82A, L90M and I84V the most frequent ones. 61.02% of the patients presented one or more mutations against the reverse transcriptase inhibitors included in their treatment. With regard to protease inhibitors, this fact was documented in 28.81% of cases, and in 23.73% of patients receiving both reverse transcriptase inhibitors and protease inhibitors. CONCLUSIONS: Although the analysis of the mutation patterns by LiPA has known limitations, the prevalence of resistances in our study was different from that reported by other authors, being lower in the P gene and higher in the RT one. Of note, a high proportion of patients showed mutations against the drugs included in their prescribed treatment.

[HIV-2 and HTLV-I/II infections in Spain]. / Infecciones por VIH-2 y HTLV-I/II en España.

Up to December 2002, a total of 56, 566 and 109 cases of human T-lymphotropic virus type 1 (HTLV-I), HTLV-II and human immunodeficiency virus type 2 (HIV-2) infection, respectively, were identified in Spain. Most HTLV-I- and HIV-2-infected subjects were immigrants from endemic areas or Spaniards who had traveled to, or had sexual contacts with natives from, these areas. In contrast, HTLV-II infection was mainly limited to Spanish intravenous drug users (IDU) who were frequently coinfected with HIV-1. Among HTLV-I-infected patients, 12 developed subacute myelopathy and 4 adult T-cell leukemia. As for the HIV-2-positive subjects, only 20 (18.3%) developed AIDS. There was no evidence of an increase in the incidence of HIV-2 and HTLV-I infections over time. In contrast, HTLV-II infection has spread in recent years among the HIV-1-positive IDU population in prisons, with a rate of 18% in some regions of Spain. Nevertheless, the prevalence of HTLV-II infection in HIV-1-positive IDU outpatients is still low (4.7%).