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.

Colorimetric RT-LAMP Detection of Multiple SARS-CoV-2 Variants and Lineages of Concern Direct from Nasopharyngeal Swab Samples without RNA Isolation.

Since, during the Coronavirus disease 19 (COVID-19) pandemic, a large part of the human population has become infected, a rapid and simple diagnostic method has been necessary to detect its causative agent, the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), and control its spread. Thus, in the present study, we developed a colorimetric reverse transcription-loop-mediated isothermal amplification (RT-LAMP) kit that allows the detection of SARS-CoV-2 from nasopharyngeal swab samples without the need for RNA extraction. The kit utilizes three sets of LAMP primers targeting two regions of ORF1ab and one region in the E gene. The results are based on the colorimetric change of hydroxynaphthol blue, which allows visual interpretation without needing an expensive instrument. The kit demonstrated sensitivity to detect between 50 and 100 copies of the viral genome per reaction. The kit was authorized by the National Administration of Drugs, Food and Technology (ANMAT) of Argentina after validation using samples previously analyzed by the gold standard RT-qPCR. The results showed a sensitivity of 90.6% and specificity of 100%, consistent with conventional RT-qPCR. In silico analysis confirmed the recognition of SARS-CoV-2 variants of concern (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427, and B.1.429), and lineages of the Omicron variant (B.1.1.529) with 100% homology. This rapid, simple, and sensitive RT-LAMP method paves the way for a large screening strategy to be carried out at locations lacking sophisticated instrumental and trained staff, as it particularly happens in regional hospitals and medical centers from rural areas.

[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.

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.

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.

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.

Implementación del test rápido para VIH en la ciudad autónoma de Buenos Aires una estrategia para facilitar el acceso al diagnostico oportuno / Implementation of Rapid Test for HIV in Buenos Aires City: A Strategy to Facilitate Access to Timely Diagnosis

INTRODUCCIÓN: El diagnóstico oportuno de la infección por VIH es una estrategia clave en el control de la epidemia. El uso de las pruebas rápidas facilita el acceso al diagnóstico en el primer nivel de atención y en espacios por fuera del sistema de salud. MÉTODOS: Se describió el proceso de implementación del test rápido para VIH en la Ciudad Autónoma de Buenos Aires (CABA), analizando indicadores epidemiológicos para evaluar el impacto sanitario. RESULTADOS: Desde el inicio de esta estrategia en 2012 y hasta 2018, el test rápido se implementó en 36 centros de la ciudad, tanto en el sistema de salud como en organizaciones de la sociedad civil. En 2014 se inició una campaña de promoción con testeos mensuales en el espacio público de distintos barrios. El número de personas sometidas a la prueba se duplicó en los centros de testeo y aumentó progresivamente en los laboratorios de los hospitales públicos, con un descenso en la proporción de diagnósticos en estadios sintomáticos. CONCLUSIONES: La implementación de la prueba rápida para el diagnóstico de VIH en CABA muestra un modelo exitoso de oferta de prestación en los puntos de atención, que facilita el acceso al tamizaje y que puede extenderse para el diagnóstico y tratamiento de otras infecciones de transmisión sexual.

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

[HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area]. / Resistencia de HIV-1 a drogas antirretrovirales en gestantes del área Metropolitana de Buenos Aires.

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Resistencia de HIV-1 a drogas antirretrovirales en gestantes del área metropolitana de Buenos Aires / HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area

Se determinó la frecuencia de mutaciones asociadas a resistencia de HIV-1 a antirretrovirales en embarazadas del área metropolitana de Buenos Aires, 2008-2014. Se incluyeron 136 mujeres con carga viral ≥ 500 copias/ml: 77 (56.6%) eran naïve; las otras 59 (43.4%) eran expuestas, ya sea con tratamiento en curso (n: 24) o previo (n: 35). Se realizó análisis de resistencia genotípica basal en plasma de pacientes naïve y con experiencia de tratamiento antirretroviral. Las mutaciones se identificaron según las listas de la Organización Mundial de la Salud y la International Antiviral Society, respectivamente. Se comparó la frecuencia de mutaciones detectadas en los subperíodos 2008-2011 vs. 2012-2014. Un total de 37 (27.2%) mujeres presentaron ≥ 1 mutación asociada a resistencia: 25/94 (26.5%) en 2008-2011 y 12/42 (28.5%) en 2012-2014 (p > 0.05). Entre las naïve, 15 (19.5%) tenían ≥ 1 mutación: 10/49 (20.4%) en el subperíodo 2008-2011 y 5/28 (17.8%) en 2012-2014 (p > 0.05). Las mutaciones encontradas en pacientes naïve estuvieron asociadas a inhibidores no nucleosídicos de la transcriptasa reversa, y, como en estudios anteriores, K103N fue la más frecuente a lo largo de todo el período. Entre las pacientes expuestas, 22/59 (37.3%) presentaron ≥ 1 mutación asociada a resistencia. Este estudio demuestra una alta frecuencia de mutaciones asociadas a resistencia que se mantuvo estable a lo largo del período. Los niveles detectados sugieren una mayor circulación en nuestro medio de cepas de HIV-1 resistentes a antirretrovirales con respecto a los niveles previamente observados en Argentina.

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load ≥ 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina.

Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.

Transmitted drug resistance in women with intrapartum HIV-1 diagnosis: a pilot epidemiological survey in Buenos Aires, Argentina.

INTRODUCTION: Surveillance of primary resistance to antiretroviral drugs is particularly important in pregnant population, in which infection by drug-resistant HIV has not only implications for maternal treatment, but could also jeopardize the efficacy of neonatal prophylaxis. We aim to describe the prevalence of resistance associated mutations (RAMs) in pregnant women with intrapartum HIV diagnosis in a public hospital of Buenos Aires, Argentina. MATERIALS AND METHODS: Prospective pilot study (period from 2008 to October 2013). Plasma samples were tested for viral load by Versant HIV-1 RNA 3.0 (bDNA) and sequenced using HIV-1 TRUGENE™Genotyping Kit (Siemens). The prevalence of RAMs was analyzed according to World Health Organization (WHO) criteria. RESULTS: Of 231 HIV-infected pregnant women assisted, 6% (n=14) had intrapartum diagnosis of HIV infection. 12 patients (85.7%) had previous pregnancies, 10 (71.4%) had inadequate prenatal care and 3 (23.1%) seroconverted during pregnancy. Maternal characteristics (expressed medians and ranges) were: age 25.5 (16-35) years; gestational age at birth: 39 (30-42) weeks; CD4 count: 500 (132-925) cells/µL; viral load: 9418 (1800-55299) copies/mL. No one had hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection; four (33.3%) had syphilis. Eight patients (57.1%) had vaginal delivery and six emergency C-section (42.9%). In six cases (46.2%), membrane rupture was spontaneous; four patients (28.6%) failed to receive intrapartum zidovudine (ZDV) infusion. In 12 patients a genotypic resistance test was performed: two (16.7%) had WHO RAMs corresponding to K103N mutation in both cases, conferring high-level resistance to nevirapine (NVP) and efavirenz. Two newborns (14.3%) were preterm. All received neonatal prophylaxis: ZDV in 1 case and combined prophylaxis (ZDV/3TC/NVP) in the remaining 13 (92.9%). All newborns were formula-fed. Two (14.3%) had congenital syphilis, one of whom died. One newborn was HIV-infected (positive proviral DNA at 24 hours of life, wild-type HIV). CONCLUSIONS: This pilot study suggests that levels of transmitted resistance in this high-risk population of pregnant women could be moderate to high. We preliminarily observed high-level resistance to NVP: if this finding is confirmed with a larger sample, it could potentially jeopardize the utility of this drug in the combined neonatal prophylaxis recommended in the absence of maternal antiretroviral therapy.

Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina.

OBJECTIVE: Our objective was to estimate primary resistance in an urban setting in a developing country characterized by high antiretroviral (ARV) coverage over the diagnosed population and also by an important proportion of undiagnosed individuals, in order to determine whether any change in primary resistance occurred in the past five years. DESIGN: We carried out a multi-site resistance surveillance study according to WHO HIV resistance guidelines, using a weighted sampling technique based on annual HIV case reports per site. METHODS: Blood samples were collected from 197 drug-naive HIV-1-infected individuals diagnosed between March 2010 and August 2011 at 20 HIV voluntary counselling and testing centres in Buenos Aires. Clinical records of enrolled patients at the time of diagnosis were compiled. Viral load and CD4 counts were performed on all samples. The pol gene was sequenced and the resistance profile determined. Phylogenetic analysis was performed by neighbour-joining (NJ) trees and bootscanning analysis. RESULTS: We found that 12 (7.9%) of the 152 successfully sequenced samples harboured primary resistance mutations, of which K103N and G190A were the most prevalent. Non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance mutations were largely the most prevalent (5.9%), accounting for 75% of all primary resistance and exhibiting a significant increase (p=0.0072) in prevalence during the past 10 years as compared to our previous study performed in 1997-2000 and in 2003-2005. Nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor primary resistance were low and similar to the one previously reported. CONCLUSIONS: Levels of primary NNRTI resistance in Buenos Aires appear to be increasing in the context of a sustained ARV coverage and a high proportion of undiagnosed HIV-positive individuals.

Atención integral de niños niñas y adolescentes con VIH / Comprehensive care of children and adolescents with HIV

Con el objetivo de mejorar el acceso a una atención integral de los niños, niñas y adolescentes con VIH, esta publicación ofrece un aporte para el trabajo de los equipos de salud comprometidos con la temática en Argentina. Si definirse estrictamente como una guía el contenido contempla las recomendaciones basadas en la evidencia y la experiencia de los principales referentes de cada área y reúne los aspecto biomédicos y socio culturales de la infección, asumiendo que se trata de una mirada indispensable para el abordaje integral de los procesos salud enfermedad. El volumen pretende ser una fuente de consulta que facilite la tarea de los pediatras y hebiatras no infectologos de adultos que frecuentemente realizan el seguimiento de adolescentes con HIV, ya que resulta necesario promover el acercamiento de las pediatrías generales a las especifidades del VIH, y de los infectologos de adultos a las necesidades en la adolescencia, para reducir los obstáculos en el circuito de atención. Fortalecer esta tarea es un escalón esencial para lograr la mejor atención de los niños, niñas y adolescentes con VIH en nuestro país, entendiendo que constituyen una población especialmente vulnerable que requiere políticas especificas para una mejor respuesta desde el sector de salud, La presente demuestra, también el resultado de una experiencia innovadora de trabajo compartido entre los organismos del estado, la sociedad científica y las agencias del Sistema de Naciones Unidas

Detection of HIV-1 dual infections in highly exposed treated patients.

BACKGROUND: Genetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B. OBJECTIVES: The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection STUDY DESIGN: Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed. RESULTS: Five dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains. CONCLUSIONS: Our results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.

Infecciones y otros problemas de salud en usuarios de pasta base de cocaina en un centro asistencial de Buenos Aires, Argentina / Infections and other health problems among coca paste users at a drug treatment center in Buenos Aires, Argentina

INTRODUCCIÓN: la pasta base de cocaína (PBC) es una forma fumable de cocaína de creciente utilización entre los jóvenes. OBJETIVO: describir el patrón de consumo de drogas, las seroprevalencias de VIH, hepatitis B (VHB), hepatitis C (VHC), sífilis y otrosproblemas de salud en usuarios de PBC en un centro asistencial de Argentina. MÉTODO: se incluyeron voluntarios mayores de 18 años, asistidos en el Centro Nacional de Reeducación Social (CENARESO)en el período 2006-2007, que consumieron PBC en los 6 meses anteriores a la entrevista y que nunca utilizaron drogas inyectables. Se aplicó un cuestionario estructurado, se tomó una muestra de sangre para serología de VIH, VHB, VHC y sífilis, y se analizó una sub-muestra de radiografías de tórax. RESULTADOS: más de la mitad de los 146 voluntarios manifestó haber fumado PBC varias veces por semana. Los participantes eran también consumidores frecuentes de cocaína en polvo (64%), cannabis (80,8%) y tranquilizantes (44,5%). Los principales problemas de salud auto-percibidos como consecuencia del consumo de PBC fueron las lesiones orales y la pérdida de peso. El 4,3% de los voluntarios resultó VIH-positivo. Las prevalencias de infección por sífilis, VHB y VHC fueron 2,7%, 5,5%, y 5,5%, respectivamente. El 16% estaba coinfectado con uno o más de los agentes estudiados. DISCUSIÓN: la prevalencia de infecciones, unida a otros problemas de salud de los usuarios de PBC, indica la necesidad de nuevas investigaciones a fin de diseñar intervenciones preventivas y terapéuticas apropiadas

INTRODUCTION: cocaine paste is a smokable form of cocaine increasingly used among young people. OBJECTIVE:to describe patterns of drugs, seroprevalences of HIV, hepatitis B (HBV), hepatitis C (HCV), syphilis and other health problems among coca paste users assisted at a drug treatment center in Argentina. METHOD: volunteers, eighteen-year-old and olderassisted at the National Center for Social Re-education (CENARESO)during 2006-2007, who had consumed coca paste over the past 6 months previous to the interview and had never injected drugs, were selected. A structured questionnaire wasused and blood was drawn to test HIV, HBV, HCV and syphilis. A sub-sample of thorax X-rays was analyzed. RESULTS: morethan half of the 146 volunteers had smoked coca paste severaltimes a week. The use of other drugs was frequently associated: sniffed cocaine 64%, cannabis 80,8%, and tranquilizers 44,5. Oral lesions and lost of weight were referred as health problems stemming from coca paste use. Out of the 146 volunteers, 4.3%resulted HIV-positive. Prevalences of infection for syphilis, HBV, and HCV were 2,7%, 5,5% and 5,5%, respectively. 16% wasco-infected with one or more infectious agents. DISCUSSION: the prevalence of infections detected, along with other clinical problems found among this coca paste users, show the need for further research, in order to design proper preventive and therapeutic interventions