Pretreatment HIV-1 Resistance in Argentina: Results from the Second Surveillance Study Following World Health Organization Guidelines (2019).

More than 62,000 individuals are currently on antiretroviral treatment within the public health system in Argentina. In 2019, more than 50% of people on ART received non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this context, the second nationwide HIV-1 pretreatment drug resistance surveillance study was carried out between April and December 2019 to assess the prevalence of HIV-1 drug resistance in Argentina using the World Health Organization guidelines. This was a nationwide cross-sectional study enrolling consecutive 18-year-old and older individuals starting ARVs at 19 ART-dispensing centers. This allowed us to estimate a point prevalence rate of resistance-associated mutations (RAMs) with a confidence interval (CI) of 5% (for the total population and for those without antiretroviral exposure). Four-hundred forty-seven individuals were included in the study. The prevalence of mutations associated with resistance was detected in 27.7% (95% CI 25.6-34.9%) of the population. For NNRTI, it was 19.6% (95% CI 16.3-24.5%), for integrase strand transfer inhibitor (INSTI) 6.1% (95% CI 6.1-11.9%), for nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) 3% (95% CI 1.9-5.9%), and for protease inhibitors 1.5% (95% CI 0.7-3.6%). Naive individuals had variants of resistance to NRTIs in 16.8% (95% CI 12.8-21.4) and 5.7% (95% CI 2.9-15.9) to INSTI. For experienced individuals, the prevalence of variants associated with resistance was 30.38% (95% CI 20.8-42.2) for NRTIs and 7.7% (95% CI 2.9-15.9) for INSTI. This study shows an increase in the frequency of nonpolymorphic RAMs associated with resistance to NNRTI. This study generates the framework of evidence that supports the use of schemes based on high genetic barrier integrase inhibitors as the first line of treatment and the need for the use of resistance test before prescribing schemes based on NNRTI. We report for the first time the presence of a natural polymorphism associated with the most prevalent recombinant viral form in Argentina and the presence of a mutation linked to first-line integrase inhibitors such as raltegravir.

Epidemiological, clinical and virological characteristics of patients with monkeypox. A retrospective study.

INTRODUCTION: The outbreak of monkeypox occurred in 2022 and led to a fast spread of the disease worldwide. The goal of this study is to describe the epidemiological, clinical, virological and evolving characteristics of the disorder. METHODS: We conducted a retrospective, observational and analytical study between July and October, 2022, in a Dermatology Unit. RESULTS: 124 subjects were included. Mean age was 31.5 years, 123 (99.2%) were men and 75 (60.5%) were HIV positive. The main transmission route was sexual and the incubation period was 7 days. The onset of the rash were the genitalia and perianal region in 74.2% of cases, and median time elapsed until the last scab fell off was 16 days. All patients developed a vesicular rash and 86.3% of them had systemic symptoms. Disease was moderate in 68.5% of patients and complications occurred most often when systemic symptoms and/or disseminated skin disease were present. Proctitis was the most frequent complication (59.4%) and its greater incidence was seen in the population with HIV. No significant difference was observed in real-time PCR cycle threshold values with regards to type of sample or duration of disease. Survival rate was 99.2% and other concomitant sexually transmitted infections were detected in 33.8% of patients. DISCUSSION: It is important to suspect the disease in subjects with high-risk sexual practices and a consistent clinical presentation. Swab samples of lesions as well as of scabs have proven useful for the diagnosis.

Introducción: El brote de viruela símica 2022 se extendió rápidamente por todo el mundo. El objetivo del presente trabajo es describir las características epidemiológicas, clínicas, evolutivas y virológicas. Métodos: Estudio retrospectivo, observacional y analítico entre julio-octubre del 2022 en pacientes atendidos en una Unidad de Dermatología. Resultados: Se incluyeron 124 individuos. La mediana de edad fue de 31.5 años, siendo 123 (99.2%) hombres y 70 (60.5%) HIV positivos. La vía principal de contagio fue la transmisión sexual y el período de incubación de 7 días. Las lesiones se iniciaron en la región genital y perianal en el 74.2% de los casos y el tiempo hasta la caída de la última costra presentó una mediana de 16 días. Todos desarrollaron exantema vesiculoso, el 86.3% de los individuos presentó síntomas sistémicos. La enfermedad fue moderada en el 68.5% de los pacientes y las complicaciones se observaron con mayor frecuencia en aquellos con síntomas sistémicos y/o enfermedad diseminada. Proctitis fue la complicación más destacada (59.4%) y su mayor incidencia se observó en la población con HIV. No hubo diferencias significativas en los valores de Ct de la qPCR al evaluar tipo de muestra procesada o tiempo de evolución de la enfermedad. La sobrevida fue del 99.2% y en el 33.8% de los pacientes se detectaron otras infecciones concomitantes de transmisión sexual. Discusión: Se debe sospechar la enfermedad en individuos con cuadro compatible y prácticas sexuales de riesgo. Las muestras de hisopado de lesiones y de costra resultaron útiles para el diagnóstico.

Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS. / Criptococosis meníngea e infección por SARS-CoV-2 en personas con VIH/SIDA

INTRODUCTION: Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. OBJECTIVES: To analyze the clinical characteristics and evolution of people living with HIV/AIDS and coinfection with cryptococcus and COVID-19 (group A) or without it (group B). MATERIALS AND METHODS: This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. RESULTS: We studied 65 people living with HIV/AIDS and with cryptococcosis infection diagnosed from April 2020 to May 2021. Fifteen patients with HIV/AIDS suffered from cryptococcosis and COVID-19, and out of these, 14 presented meningitis (group A), while 28 suffered from meningeal cryptococcosis, but did not have COVID-19 (group B). CONCLUSIONS: No statistically significant differences were observed between the two groups (A and B) considering: intracranial hypertension, presence of Cryptococcus antigens in cerebrospinal fluid, sensorium deterioration or mortality. The detection of Cryptococcus antigens in serum by lateral flow assay was highly effective to rapidly diagnose cryptococcosis in patients with HIV/AIDS who also developed COVID-19. Patients of both groups consulted for cryptoccocosis sometime after, in comparison with the pre-pandemic cases related to this infection.

Introducción: Las infecciones fúngicas en pacientes con COVID-19 fue uno de los temas más debatidos durante la pandemia. Objetivo: Analizar las características clínicas y la evolución de personas con VIH/SIDA que presentaron la asociación de criptococosis meníngea y COVID-19 (grupo A), y compararlas con aquellas personas con VIH/SIDA que padecieron criptococosis meníngea, pero sin infección de COVID-19 (grupo B). Materiales y métodos: Se realizó un estudio analítico y retrospectivo en el que se revisaron las historias clínicas de pacientes que padecieron criptococosis meníngea entre abril de 2020 y mayo de 2021. Resultados: Se estudiaron 65 pacientes con HIV/SIDA y con criptococosis, diagnosticados entre abril de 2020 y mayo de 2021 (63 habían desarrollado sida y 2 eran negativos para VIH). De estos, 15 de los pacientes con sida padecían criptococosis y COVID-19, y 14 presentaban meningitis (grupo A), mientras que 28 pacientes padecieron criptococosis meníngea, pero no tuvieron COVID-19 (grupo B). Conclusiones: No se observaron diferencias estadísticamente significativas, entre los dos grupos, respecto a la hipertensión intracraneal, la presencia de antígenos de criptoccoco en líquido cefalorraquídeo, el deterioro del sensorio o la mortalidad. La detección de antígenos de Cryptococcus en suero por ensayo de flujo lateral fue efectiva para diagnosticar rápidamente criptococosis en personas con VIH/sida y con infección de COVID-19. Se observó que los pacientes de ambos grupos consultaron tarde por criptococosis en comparación con los casos prepandémicos de esta infección.

Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS / Criptococosis meníngea e infección por SARS-CoV-2 en personas con VIH/SIDA

Introduction. Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. Objectives. To analyze the clinical characteristics and evolution of people living with HIV/ AIDS and coinfection with cryptococcus and COVID-19 (group A) or without it (group B). Materials and methods. This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. Results. We studied 65 people living with HIV/AIDS and with cryptococcosis infection diagnosed from April 2020 to May 2021. Fifteen patients with HIV/AIDS suffered from cryptococcosis and COVID-19, and out of these, 14 presented meningitis (group A), while 28 suffered from meningeal cryptococcosis, but did not have COVID-19 (group B). Conclusions. No statistically significant differences were observed between the two groups (A and B) considering: intracranial hypertension, presence of Cryptococcus antigens in cerebrospinal fluid, sensorium deterioration or mortality. The detection of Cryptococcus antigens in serum by lateral flow assay was highly effective to rapidly diagnose cryptococcosis in patients with HIV/AIDS who also developed COVID-19. Patients of both groups consulted for cryptoccocosis sometime after, in comparison with the pre-pandemic cases related to this infection.

Introducción. Las infecciones fúngicas en pacientes con COVID-19 fue uno de los temas más debatidos durante la pandemia. Objetivo. Analizar las características clínicas y la evolución de personas con VIH/SIDA que presentaron la asociación de criptococosis meníngea y COVID-19 (grupo A), y compararlas con aquellas personas con VIH/SIDA que padecieron criptococosis meníngea, pero sin infección de COVID-19 (grupo B). Materiales y métodos. Se realizó un estudio analítico y retrospectivo en el que se revisaron las historias clínicas de pacientes que padecieron criptococosis meníngea entre abril de 2020 y mayo de 2021. Resultados. Se estudiaron 65 pacientes con HIV/SIDA y con criptococosis, diagnosticados entre abril de 2020 y mayo de 2021 (63 habían desarrollado sida y 2 eran negativos para VIH). De estos, 15 de los pacientes con sida padecían criptococosis y COVID-19, y 14 presentaban meningitis (grupo A), mientras que 28 pacientes padecieron criptococosis meníngea, pero no tuvieron COVID-19 (grupo B). Conclusiones. No se observaron diferencias estadísticamente significativas, entre los dos grupos, respecto a la hipertensión intracraneal, la presencia de antígenos de criptoccoco en líquido cefalorraquídeo, el deterioro del sensorio o la mortalidad. La detección de antígenos de Cryptococcus en suero por ensayo de flujo lateral fue efectiva para diagnosticar rápidamente criptococosis en personas con VIH/sida y con infección de COVID-19. Se observó que los pacientes de ambos grupos consultaron tarde por criptococosis en comparación con los casos prepandémicos de esta infección.

Molecular and biological characterization of hepatitis B virus subgenotype F1b clusters: Unraveling its role in hepatocarcinogenesis.

Hepatitis B virus (HBV) subgenotype F1b infection has been associated with the early occurrence of hepatocellular carcinoma in chronically infected patients from Alaska and Peru. In Argentina, however, despite the high prevalence of subgenotype F1b infection, this relationship has not been described. To unravel the observed differences in the progression of the infection, an in-depth molecular and biological characterization of the subgenotype F1b was performed. Phylogenetic analysis of subgenotype F1b full-length genomes revealed the existence of two highly supported clusters. One of the clusters, designated as gtF1b Basal included sequences mostly from Alaska, Peru and Chile, while the other, called gtF1b Cosmopolitan, contained samples mainly from Argentina and Chile. The clusters were characterized by a differential signature pattern of eight nucleotides distributed throughout the genome. In vitro characterization of representative clones from each cluster revealed major differences in viral RNA levels, virion secretion, antigen expression levels, as well as in the localization of the antigens. Interestingly, a differential regulation in the expression of genes associated with tumorigenesis was also identified. In conclusion, this study provides new insights into the molecular and biological characteristics of the subgenotype F1b clusters and contributes to unravel the different clinical outcomes of subgenotype F1b chronic infections.

[Skin manifestations in patients with COVID-19. A prospective study]. / Manifestaciones cutáneas en pacientes con COVID-19. Estudio prospectivo.

As of March 2020, skin lesions associated with COVID-19 have been described. The objectives of the study were to characterize the skin lesions in these patients, analyze their temporal relationship, association with the severity of the disease, extracutaneous symptoms and laboratory parameters. A prospective, observational, analytical and cross-sectional study was conducted in hospitalized patients diagnosed with COVID-19. Dermatoses were classified as primary and secondary. Forty-five patients were included, 44.4% with primary dermatoses and 53.3% with secondary lesions. The mean age was 46 years (SD: 17), with a male predominance (68.9%). The primary lesions appeared after a median of 5 days (IQR: 3-10) from the onset of COVID-19 symptoms and the secondary ones after 14.5 days (IQR: 7-20). The primary dermatoses found were maculopapular rash (65%), urticarial (20%, half with vesicular lesions), livedo reticular (10%) and purpura (5%). The most frequent secondary dermatoses were adverse drug reactions (37.1%) and infectious dermatoses (25.9%). Maculopapular rash was associated with moderate COVID-19 and pressure injuries with severe COVID-19 (p < 0.05). The finding of neutrophilia was higher among those with secondary infectious dermatoses (p < 0.05). No significant differences were found when evaluating other laboratory parameters. This work shows the skin manifestations in patients hospitalized with COVID-19 in our environment. The most prevalent pattern was the maculopapular rash that was associated with the moderate form of the disease. The appearance of lesions 2 weeks after the onset of COVID-19 symptoms was associated with secondary dermatoses.

Desde marzo 2020 se describieron lesiones cutáneas asociadas a COVID-19. Los objetivos del estudio fueron caracterizar las lesiones cutáneas en estos pacientes, analizar su relación temporal, asociación con la gravedad de la enfermedad, los síntomas extracutáneos y parámetros de laboratorio. Es un estudio prospectivo, observacional, analítico y de corte transversal, en internados con diagnóstico de COVID-19. Se catalogaron las dermatosis en primarias y secundarias. Se incluyeron 45 pacientes, 44.4% con dermatosis primarias y 53.3% con lesiones secundarias. La edad media fue de 46 años (DS: 17), con predominio del sexo masculino (68.9%). Las lesiones primarias aparecieron luego de una mediana de 5 días (RIC: 3-10) del inicio de los síntomas de COVID-19 y las secundarias luego de 14.5 días (RIC: 7-20). Las dermatosis primarias fueron: exantema maculopapuloso (65%), urticariforme (20%, la mitad con lesiones vesiculosas), livedo reticular (10%) y púrpura (5%). Las dermatosis secundarias más frecuentes fueron reacciones adversas a fármacos (37.1%) y dermatosis infecciosas (25.9%). El exantema maculopapuloso se asoció a COVID-19 moderado y las lesiones por presión a COVID-19 grave (p < 0.05). El hallazgo de neutrofilia fue mayor entre aquellos con dermatosis infecciosas secundarias (p < 0.05). No se encontraron diferencias significativas al evaluar otros parámetros de laboratorio, ni síntomas extracutáneos. Este trabajo muestra las manifestaciones cutáneas en internados con COVID-19. El patrón más prevalente fue el exantema maculopapuloso que se asoció con la forma moderada de la enfermedad. La aparición de lesiones luego de las 2 semanas del inicio de los síntomas de COVID-19 se asoció a dermatosis secundarias.

Making Visible HTLV Infection in a Non-endemic Area of Argentina.

In Argentina, the human T-cell lymphotropic virus type 1 (HTLV-1) infection has been documented mainly among blood banks with a prevalence of ~0.02-0.046% for Buenos Aires city, 0.8% for the northeast, and 1% for the northwest; both areas are considered endemic for HTLV-2 and 1, respectively. Policies and specific guidelines for testing blood donors for HTLV are included since 2005. Screening for antibodies is performed at blood banks and confirmatory testing is performed at reference laboratories. There are no specific recommendations for the assistance of communities and individuals affected, nor referral to specialized clinics on the HTLV infection. In 2016, as a strategy of intervention, we opened a specialized clinical attendance in a referral infectious diseases public hospital for the comprehensive approach to patients with HTLV, offering follow-up and counseling for patients and their families for the early diagnosis of HTLV-1/2 and related diseases. During the study, 124 patients with presumptive HTLV positive diagnosis from blood bank, symptomatic patients (SPs), relatives, and descendants visited the unit. A total of 46 patients were HTLV positive (38 HTLV-1 and 8 HTLV-2). There were nine SPs (2 adult T-cell leukemia/lymphoma [ATL] and 7 HTLV-1-associated myelopathy/tropical spastic paraparesis [HAM/TSP]). All patients with HTLV-1 and-2 were offered to study their relatives. Two out of 37 (5.4%) descendants tested were positive for HTLV-1. Sexual partners were studied; among 6 out of 11 couples (54.5%) were found positive (5 HTLV-1 and 1 HTLV-2). Other relatives, such as mothers (1/2) and siblings (1/6), were positive for HTLV-1. According to the place of birth among HTLV-1 carriers, 58% were born in an endemic area or in countries where HTLV infection is considered endemic while for HTLV-2 carriers, 12.5% were born in an endemic area of Argentina. The proviral load (pVL) was measured in all, patients with HTLV-1 being higher in symptomatic compared with asymptomatic carriers. In addition, two pregnant women were early diagnosed during their puerperium and breastmilk replacement by formula was indicated. Inhibition of lactation was also indicated. Our study provides tools for a multidisciplinary approach to the infection and reinforces the importance of having specialized clinical units in neglected diseases, such as HTLV for counseling, clinical and laboratory follow-up, and providing useful information for patients for self-care and that of their families.

Manifestaciones cutáneas en pacientes con COVID-19. Estudio prospectivo / Skin manifestations in patients with COVID-19. A prospective study

Resumen Desde marzo 2020 se describieron lesiones cutáneas asociadas a COVID-19. Los objetivos del estudio fueron caracterizar las lesiones cutáneas en estos pacientes, analizar su relación temporal, asociación con la gravedad de la enfermedad, los síntomas extracutáneos y parámetros de laboratorio. Es un estudio prospectivo, observacional, analítico y de corte transversal, en internados con diagnóstico de COVID-19. Se catalogaron las dermatosis en primarias y secundarias. Se incluyeron 45 pacientes, 44.4% con dermatosis primarias y 53.3% con lesiones secundarias. La edad media fue de 46 años (DS: 17), con predominio del sexo masculino (68.9%). Las lesiones primarias aparecieron luego de una mediana de 5 días (RIC: 3-10) del inicio de los síntomas de COVID-19 y las secundarias luego de 14.5 días (RIC: 7-20). Las dermatosis primarias fueron: exantema maculopapuloso (65%), urticariforme (20%, la mitad con lesiones vesiculosas), livedo reticular (10%) y púrpura (5%). Las dermatosis secundarias más frecuentes fueron reacciones adversas a fármacos (37.1%) y dermatosis infecciosas (25.9%). El exantema maculopapuloso se asoció a COVID-19 moderado y las lesiones por presión a COVID-19 grave (p < 0.05). El hallazgo de neutrofilia fue mayor entre aquellos con dermatosis infecciosas secundarias (p < 0.05). No se encontraron diferencias significativas al evaluar otros parámetros de laboratorio, ni síntomas extracutáneos. Este trabajo muestra las manifestaciones cutáneas en internados con COVID-19. El patrón más prevalente fue el exantema maculopapuloso que se asoció con la forma moderada de la enfermedad. La aparición de lesiones luego de las 2 semanas del inicio de los síntomas de COVID-19 se asoció a dermatosis secundarias.

Abstract As of March 2020, skin lesions associated with COVID-19 have been described. The objectives of the study were to char acterize the skin lesions in these patients, analyze their temporal relationship, association with the severity of the disease, extracutaneous symptoms and laboratory parameters. A prospective, observational, analytical and cross-sectional study was conducted in hospitalized patients diagnosed with COVID-19. Dermatoses were clas sified as primary and secondary. Forty-five patients were included, 44.4% with primary dermatoses and 53.3% with secondary lesions. The mean age was 46 years (SD: 17), with a male predominance (68.9%). The primary lesions appeared after a median of 5 days (IQR: 3-10) from the onset of COVID-19 symptoms and the secondary ones after 14.5 days (IQR: 7-20). The primary dermatoses found were maculopapular rash (65%), urticarial (20%, half with vesicular lesions), livedo reticular (10%) and purpura (5%). The most frequent secondary dermatoses were adverse drug reactions (37.1%) and infectious dermatoses (25.9%). Maculopapular rash was associated with moderate COVID-19 and pressure injuries with severe COVID-19 (p < 0.05). The finding of neutrophilia was higher among those with secondary infectious dermatoses (p < 0.05). No significant differences were found when evaluating other laboratory parameters. This work shows the skin manifestations in patients hospitalized with COVID-19 in our environment. The most prevalent pattern was the maculopapular rash that was associated with the moderate form of the disease. The appearance of lesions 2 weeks after the onset of COVID-19 symptoms was associated with secondary dermatoses.

Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials.

BACKGROUND: Shortages of component two of Sputnik V vaccine (rAd5) are delaying the possibility of achieving full immunisation. The immunogenic response associated with the use of alternative schemes to complete the scheme was not explored. METHODS: We did two non-inferiority randomized clinical trials with outcomes measures blinded to investigators on adults aged 21-65 years, vaccinated with a single dose of rAd26 ≥ 30 days before screening and no history of SARS-CoV-2. Participants were assigned (1:1:1:1:1) to receive either rAd5; ChAdOx1; rAd26; mRNA-1273 or BBIBP-CorV. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-spike IgG concentration at 28 days after the second dose, when comparing rAd26/rAd5 with rAd26/ChAdOx1, rAd26/rAd26, rAd26/mRNAmRNA-1273 and rAd26/BBIBP-CorV. Serum neutralizing capacity was evaluated using wild type SARS-CoV-2 reference strain 2019 B.1. The safety outcome was 28-day rate of serious adverse. The primary analysis included all participants who received ≥ 1 dose. The studies were registered with NCT04962906 and NCT05027672. Both trials were conducted in Buenos Aires, Argentina. FINDINGS: Between July 6 and August 3, 2021, 540 individuals (age 56·7 [SD 7·3]; 243 (45%) women) were randomly assigned to received rAd5 (n=150); ChAdOx1 (n=150); rAd26 (N=87); mRNAmRNA-1273 (n=87) or BBIBP-CorV (n=65). 524 participants completed the study. As compared with rAd26/rAd5 (1·00), the GMR (95%CI) at day 28 was 0·65 (0·51-0·84) among those who received ChAdOx1; 0·47 (0·34-0·66) in rAd5; 3·53 (2·68-4·65) in mRNA-1273 and 0·23 (0·16-0·33) in BBIBP-CorV. The geometric mean (IU/ml) from baseline to day 28 within each group increased significantly with ChAdOx1 (4·08 (3·07-5·43)); rAd26 (2·69 (1·76-4·11)); mRNA-1273 (21·98 (15·45-31·08)) but not in BBIBP-CorV (1·22 (0·80-1·87)). INTERPRETATION: Except for mRNA-1273 which proved superior, in all other alternatives non-inferiority was rejected. Antibody concentration increased in all non-replicating viral vector and RNA platforms. FUNDING: The trials were supported (including funding, material support in the form of vaccines and testing supplies) by the Buenos Aires City Government.

Biological Characterization of Hepatitis B virus Genotypes: Their Role in Viral Replication and Antigen Expression.

Hepatitis B virus (HBV) inter-host evolution has resulted in genomic diversification reflected in the existence of nine genotypes (A-I) and numerous subgenotypes. There is growing evidence that genotypes influence HBV natural history, clinical outcomes, and treatment response. However, the biological characteristics underlying these differences have not yet been established. By transfecting HuH-7 cells with unit-length constructs of genotypes A2, B2, C1, D1, and F1b, we identified major differences in HBV replicative capacity and antigen expression across genotypes. Genotypes B2 and F1b showed a 2-fold increase in cccDNA levels compared to the other genotypes (p<0.005). Genotype A2 expressed the lowest pgRNA levels, with a 70-fold decrease in relation to the other genotypes (p<0.0001), while genotype B2 showed the lowest Precore RNA levels, with a 100-fold reduction compared to genotype A2 (p<0.0001). The highest intracellular HBV DNA levels were observed for genotype B2 and the lowest for genotypes A2 and C1 (p<0.0001). Regarding antigen expression, genotype F1b secreted the highest HBsAg levels and genotype D1 the lowest (p<0.0001), while genotypes A2 and B2 showed the highest intracellular HBsAg levels (p<0.0001). Interestingly, genotype C1 secreted the highest HBeAg levels, while genotype A2 showed the highest intracellular levels (p<0.0001). Finally, the analysis of the intra/extracellular antigen ratios revealed that most genotypes retained intracellularly 5-20% of the antigens, except the genotype A2 that retained 50% of the total expressed antigens. In conclusion, this study provides new insights into the biological characteristics of HBV genotypes, being the first study to comparatively analyze European (A and D) and Asian (B and C) genotypes with the Latin American (F) genotype. The differences in HBV replication and antigen expression might contribute to understand the differential role of genotypes in pathogenesis.

Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: Association with the genetic ancestry of the population.

BACKGROUND: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations. OBJECTIVES: The aims of this study were to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina, and to establish potential associations with pathogenic conditions and the genetic ancestry of the population. STUDY DESIGN: A total of 101 HIV-1 infected subjects, 93 Kaposi's Sarcoma (KS) patients and 411 blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). HHV-8 DNA was detected by ORF-26 PCR in whole blood, saliva and FFPE tissues. Then, ORF-26 and ORF-K1 were analyzed for subtype assignment. Mitochondrial DNA and Y chromosome haplogroups, as well as autosomal ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences. RESULTS: HHV-8 was detected in 50.7%, 59.2% and 8% of samples from HIV-1 infected subjects, KS patients and blood donors, respectively. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. The prevalence of subtype J was more commonly observed among KS patients when compared to the other groups. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p = 0.004), whereas subtype J was related to non-Native American haplogroups (p < 0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina. CONCLUSIONS: These results give evidence of the geographic circulation of HHV-8 in Argentina, suggest the association of ORF-26 subtype J with KS development and provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina.

Exantema asociado a COVID-19 / COVID-19 skin rash

A partir de marzo de 2020 se han empezado a describir lesiones cutáneas asociadas a COVID-19 que fueron agrupadas en patrones y se relacionaron con la severidad y la temporalidad de la enfermedad. Se presenta el caso de un paciente con COVID-19 leve y lesiones cutáneas que pueden atribuirse a la infección. Se realiza una revisión de las manifestaciones cutáneas asociadas a COVID-19 y la interpretación de los diagnósticos diferenciales que se pensaron en el paciente

Since March 2020, skin lesions associated with COVID-19 have begun to be described. These were grouped into patterns, and were related to the severity and temporality of the disease. A patient with mild COVID-19 and skin lesions that can be attributed to the infection is presented. A review of the cutaneous manifestations associated with COVID-19 and the interpretation of the differential diagnoses that were thought of in the patient is carried out.

Relevance of HTLV-1 proviral load in asymptomatic and symptomatic patients living in endemic and non-endemic areas of Argentina.

HTLV-1 proviral load (pVL) in peripheral blood mononuclear cell (PBMCs) is proposed as a marker of disease progression but its role still remains controversial. The aim of this study was to evaluate the levels of HTLV-1 pVL in symptomatic patients and asymptomatic HTLV-1 carriers. In this cross-sectional study the pVL was measured by Real Time PCR in 102 asymptomatic carriers and 22 symptomatic patients (5ATLL, 15 TSP and 2 uveitis). We observed that the HTLV-1 pVL was significantly higher in symptomatic patients (median = 4.99 log10 HTLV-1 copies /106 PBMCs) compared to asymptomatic HTLV-1 carriers (median = 4.38 log10 HTLV-1 copies /106 PBMCs; p = 0.0030). A wide variation on the HTLV-1 pVL levels among asymptomatic HTLV-1 carriers was observed with some pVL as high as those observed in symptomatic patients. The asymptomatic HTLV-1 carriers were divided according to the place of birth and the highest levels of pVL were detected among patients from endemics areas from the North of Argentina. Our results reinforce the usefulness of the proviral load would be a prognostic marker of HTLV-1 disease progression. Moreover, host, viral or socio-environmental factors cannot be excluded as determinant of high proviral load.

Infección por HPV de alto riesgo y lesiones intraepiteliales anales en hombres HIV positivos que tienen sexo con hombres / High Risk GPV infection and anal Intraepithelial lesions in HIV positive men who have sex whit men

Introducción: El cáncer anal, asociado a la infección con virus de papiloma humano de alto riesgo (HPV-AR), es muy frecuente en hombres que tienen sexo con hombres (HSH) HIV+. Objetivo: Evaluar frecuencia de infección por HPV-AR, genotipos y lesiones asociadas, y factores asociados.Materiales y métodos: Estudio en HSH HIV+ (septiembre 2012-marzo 2014, Hospital Fernández). Se recogió información demográfica, de HIV, HPV y prácticas sexuales. Se realizó citología anal, detección de HPV-AR (HC2 High-Risk HPV DNA, Digene®) y genotipificación en las muestras HPV-AR+ (Inno Lipa®, Fujirebio). Los pacientes firmaron consentimiento informado. Se indicó tratamiento según resultados. Resultados: Completaron el estudio 57 pacientes. Mediana de edad: 40 años (rango intercuartil [RIC]: 29-45); de CD4: 444 cels/mm3 (RIC: 345-568); 77% recibían tratamiento antirretroviral, 68% con carga viral no detectable. Citologías: negativas (24%); lesión intraepitelial de bajo grado (54%); lesión intraepitelial de alto grado (20%); ASCUS (2%). El 80% fue HPV-AR+. Los pacientes con diagnóstico de HPV-AR (p=0,006) y de lesión intraepitelial tuvieron CD4 <500 cels/mm3 con más frecuencia (p=0,030). Los pacientes con HPV-AR tuvieron mayor frecuencia de carga viral detectable (p=0,020, prueba de Fisher). El porcentaje de pacientes con uso consistente de preservativo fue mayor entre los pacientes sin lesión citológica (p=0,026). Genotipos de alto riesgo más frecuentes: HPV-16 (51%), HPV-31 (44%) y HPV-51 (40%); de bajo riesgo: HPV-6 (47%) y HPV-44 (35%).Conclusiones: Se encontró elevada frecuencia de lesión citológica (76%) y de HPV-AR (80%). Es necesario establecer estrategias de prevención en esta población incluyendo tamizaje, vacunación y promoción de sexo seguro.Palabras clave: HIV, lesión intraepitelial anal, HPV, citología anal, tamizaje de cáncer anal, hombres que tienen sexo con hombre

ntroduction: Anal cancer, associated with the infection with high risk Human Papillomavirus (HR-HPV), is very frequent among HIV+ men who have sex with men (MSM). Objective: To evaluate the frequency of HR-HPV infection, presence of HPV genotypes and HPV- associated lesions and associated factors.Methods: Study in HIV+ MSM (September 2012- March 2014, Hospital Fernández). Demographical, HIV, HPV and sexual behaviour information was collected. Cytology, HR-HPV detection (HC2 High-Risk HPV DNA, Digene ®) and genotyping was performed on samples positive for HR-HPV (Inno Lipa®, Fujirebio). All patients signed informed consent. Treatment was provided according to results.Results: Fifty-seven patients completed the study. Median age was 40 years old (interquartile range [IQR]: 29-45); median CD4 cell count: 444 cels/mm3 (IQR: 345-568); 77% were under ARV treatment, 68% with undetectable viral load. Cytology results: 24% negative, 54% low grade intraepithelial lesion, 20% high grade intraepithelial lesion, 2% ASCUS. Eighty percent were HR-HPV+. Patients with HR-HPV (p=0,006) and diagnosis of intraepithelial lesion had more frequent CD4 <500 cels/mm3 (p=0,030). Patients diagnosed with HR-HPV had a higher frequency of detectable viral load (p=0,020, prueba de Fisher). The percentage of patients with consistent condom use was higher among patients without cytological lesion (p=0,026).Most frequent high risk genotypes: HPV-16 (51%), HPV-31 (44%) and HPV-51 (40%); low risk genotypes HPV-6 (47%) and HPV-44 (35%).Conclusions: There was high frequency of cytological lesions (76%) and HR-HPV (80%). It is necessary to promote prevention strategies in this population including screening, vaccine and safe sex promotion

Identificación de citomegalovirus y varicela zoster virus en lesiones cutáneas en una paciente con sida Presentación de un caso y revisión de la bibliografía / CENTRAL NERVOUS SYSTEM INVOLVEMENT DUE TO HERPESVIRUS REACTIVATION IN AIDS PATIENTS

Las reactivaciones de las infecciones latentes por virus de la familia Herpes originan variadas y graves manifestaciones clínicas en los enfermos con sida. Las lesiones mucocutáneas son comunes en las infecciones por Herpes simple 1 y 2 y por varicela-zóster (VZV). En cambio, son infrecuentes en infecciones por citomegalovirus (CMV). La coexistencia de más de un patógeno en la misma lesión ha sido escasamente referida en la literatura. Presentamos una paciente con enfermedad VIH/sida avanzada que desarrolló lesiones cutáneas diseminadas, en una de las cuales se identificó por técnica de PCR el genoma de VZV y CMV. El diagnóstico precoz seguido del tratamiento antiherpético y la reconstitución inmunológica alcanzada con la TARGA pueden mejorar el pronóstico de esta clase de pacientes

The reactivation of latent infections due to Herpesviridae is associated with a serious compromise in HIV/AIDS patients. Mucocutaneous lesions are frequent in disseminated infections due to Herpes simple 1 and 2 and varicella-zoster virus (VZV). However, cutaneous involvement is rare in cytomegalovirus infections. The coexistence of VZV and CMV in the same lesion has been little reported in the literature. Here, we describe a female with advanced HIV/AIDS disease who developed disseminated cutaneous lesions, in one of yhem we detected VZV and CMV by PCR. Early diagnosis followed by specific antiherpetic therapy and the immune reconstitution associated with HAART can improve the prognosis of these kind of patients.

MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF ELEVEN CASES AND REVIEW OF THE LITERATURE / Meningoencefalite pelo vírus varicela-zoster em pacientes com AIDS. Relato de onze casos e revisão da literatura

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

As complicações neurológicas do vírus varicela-zoster (VVZ) são pouco frequentes e incluem vários quadros clínicos. A reativação do VVZ em pacientes com AIDS é geralmente associada com meningoencefalite aguda e grave. Nós relatamos os dados epidemiológicos, clínicos e virológicos de onze pacientes consecutivos com diagnóstico de HIV/AIDS e comprometimento do sistema nervoso central (SNC) devido ao VVZ. Todos os pacientes eram do sexo masculino e soropositivos para HIV. O principal fator de risco para a infecção pelo HIV foi o contato sexual sem proteção. A mediana da contagem de células CD4 T foi de 142 cel/µL. Todos apresentavam sinais e sintomas devido à meningoencefalite. Seis pacientes (54,5%) apresentaram pleiocitose; todos apresentaram hiperproteinorraquia com mediana de 2,1 g/dL. A reação em cadeia da polimerase de amostra do líquido cefalorraquidiano foi positiva para VVZ em todos eles. Todos os pacientes foram tratados com aciclovir por via intravenosa em doses de 30 mg/kg/dia durante 21 dias. A sobrevida global foi de 63% (sete de 11 pacientes). Os quatro pacientes mortos tiveram uma escassa resposta celular no LCR abaixo da mediana para este parâmetro. O VVZ deve ser incluído entre os patógenos oportunistas que podem comprometer o SNC com meningoencefalite difusa e grave em pacientes com doença avançada por HIV/SIDA.

Hepatitis B virus genotype distribution and genotype-specific BCP/preCore substitutions in acute and chronic infections in Argentina.

AIM: In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections). RESULTS: Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896. DISCUSSION: HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.

MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF ELEVEN CASES AND REVIEW OF THE LITERATURE.

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.