Registro argentino de COVID-19 en VIH (Estudio COVIDARE): características clínicas, epidemiológicas y factores asociados a hospitalización / Argentine Registry of COVID-19 in HIV (COVIDARE Study): clinical and epidemiological characteristics and factors associated with hospitalization

INTRODUCCIÓN: Existe controversia con respecto a los factores que determinan un mayor riesgo de gravedad y complicaciones por COVID-19 en personas que viven con VIH (PVVIH). Asimismo, hay datos limitados sobre el impacto de la vacunación contra SARS-CoV-2 en la hospitalización en esta población. OBJETIVOS: Describir las características clínicas y evolutivas de COVID-19 en PVVIH; Evaluar factores de riesgo para hospitalización; Evaluar el impacto de la vacunación en la hospitalización. Pacientes y MÉTODOS: Estudio observacional, prospectivo, multicéntrico (septiembre de 2020 a junio de 2022). Se registraron variables clínicas, inmunovirológicas, tratamiento antirretroviral (TARV), vacunación contra SARS-CoV-2 y hospitalización en PVVIH con COVID-19. Se realizaron análisis uni y multivariados examinando factores asociados a hospitalización utilizando dos modelos: primer modelo (sin vacunación) y segundo modelo (vacunación, mínimo una dosis). RESULTADOS: Se incluyeron 1.201 PVVIH. La mediana de edad fue 45 años. El 65,3% fueron hombres; el 38,7% presentó comorbilidades. Recibía TARV el 92,8% y presentó carga viral (CV) indetectable el 83,1%. La mediana de linfocitos T CD4+ fue de 600 céls/mm3. El 95,7% presentó síntomas. Las tasas de hospitalización, ingreso a UCI, requerimiento de oxígeno y muerte fueron 17,8%, 2,8%, 10,7% y 1,39%, respectivamente. De acuerdo con el análisis multivariado para el primer modelo, la edad > 60 años y las comorbilidades se asociaron a mayor riesgo de hospitalización, mientras que el sexo femenino y un recuento de linfocitos T CD4+ > 500 céls/mm3 tuvieron un efecto protector. En el segundo modelo sólo las comorbilidades se relacionaron con un mayor riesgo de hospitalización mientras que la vacunación y células CD4+ > 500 céls/mm3 la redujeron. CONCLUSIONES: En PVVIH las comorbilidades se asociaron con mayor tasa de hospitalización, mientras que tener linfocitos T CD4+ elevados y estar vacunado tuvieron un efecto protector. El TARV y la CV no tuvieron impacto en modelo alguno mientras que la edad y el sexo solo influyeron cuando no se consideró la vacunación.

BACKGROUND: There is controversy regarding the factors that determine a greater risk of severity and complications from COVID-19 in people living with HIV (PLHIV). Likewise, there are limited data on the impact of SARS-CoV-2 vaccination on hospitalization in this population. AIMS: To describe clinical characteristics and outcome of COVID-19 in PLHIV; To assess risk factors for hospitalization; To evaluate the impact of vaccination on hospitalization. METHODS: Multicenter, prospective, observational study (September 2020 to June 2022). Clinical and immunovirological variables, antiretroviral treatment (ART), SARS-CoV-2 vaccination, and hospitalization in PLHIV with COVID-19 were recorded. Univariate and multivariate analyzes were performed examining factors associated with hospitalization using two models: first model (without vaccination) and second model (vaccination, minimum one dose). RESULTS: 1,201 PLHIV were included. The median age was 45 years. 65.3% were men; 38.7% presented comorbidities. 92.8% received ART and 83.1% presented undetectable viral load (VL). The median CD4+ T-cell count was 600/mm3. 95.7% presented symptoms. The rates of hospitalization, ICU admission, oxygen requirement, and death were 17.8 %, 2.8%, 10.7% and 1.39%, respectively. According to the multivariate analysis for the first model, age > 60 years and comorbidities were associated with a higher risk of hospitalization, while female sex and CD4+ > 500/mm3 had a protective effect. In the second model, only the comorbidities were associated with a higher risk of hospitalization, while vaccination and CD4+ > 500/mm3 reduced it. CONCLUSIONS: in PLHIV, comorbidities were associated with a higher hospitalization rate, while having elevated CD4+ T-cell counts and being vaccinated had a protective effect. ART and VL had no impact in any model, while age and sex only had an influence when vaccination was not considered.

Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV.

Tenofovir has been hypothesized to be effective against COVID-19 and is available as two prodrugs, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both part of antiretroviral therapy (ART) regimens. People living with human immunodeficiency virus (PLWH) might be at higher risk for COVID-19 progression; however, information about the impact of tenofovir on COVID-19 clinical outcomes remains controversial. The COVIDARE is a prospective observational multicentric study in Argentina. PLWH with COVID-19 were enrolled from September 2020 to mid-June 2022. Patients were stratified according to baseline ART into those with tenofovir (TDF or TAF) and those without. Univariate and multivariate analyses were performed to evaluate the impact of tenofovir vs. non-tenofovir-containing regimens on major clinical outcomes. Of the 1155 subjects evaluated, 927 (80%) received tenofovir-based ART (79% TDF, 21% TAF) whilst the remaining population was under non-tenofovir regimens. The non-tenofovir group had older age and a higher prevalence of heart and kidney disease. Regarding the prevalence of symptomatic COVID-19, tomographic findings, hospitalization, and mortality, no differences were observed. The oxygen therapy requirement was higher in the non-tenofovir group. In the multivariate analyses, a first model with adjustment for viral load, CD4 T-cell count, and overall comorbidities showed that oxygen requirement was associated with non-tenofovir ART. In a second model with adjustment by chronic kidney disease, tenofovir exposure was not statistically significant.

[Assessment of the humoral immunity induced by Sputnik V COVID-19 vaccine (Gam-COVID-Vac) in healthcare workers]. / Evaluación de la respuesta de los anticuerpos IGG específicos contra SARS-CoV-2 en el personal de salud con el esquema completo de la vacuna Sputnik V (Gam-COVID-Vac).

Background: Vaccination for COVID-19 in healthcare workers (HCW) is essential to protect one of the populations most exposed to this disease. However, data on the humoral response rate to the vaccine and the factors associated with it in this population are limited. Therefore, we aimed to evaluate the antibody response against SARS-CoV-2 in HCWs with complete Sputnik V vaccine scheme and factors associated with an increased antibody response. Material and methods: Prospective study to evaluate the anti-SARS-CoV-2 humoral response in HCWs vaccinated with two doses of the Sputnik V vaccine (April-July 2021). The assessment of anti-Spike IgG antibodies in plasma was performed using the COVIDAR IgG enzyme-linked immunosorbent assay. A logistic regression was performed to identify independent factors associated with a positive IgG serology test and an elevated antibody response. Results: A total of 630 HCWs were enrolled. Median age (IQR): 47 years (35-56). Female sex: 462 (73.33%). Previous COVID-19: 158 (25%). The median interval time between vaccine doses was 3 (3-4) weeks. Positive serology was observed in 607 (96.35%) HCWs. In the multivariate analysis, a history of systemic reactogenicity was identified as an independent variable associated with a positive serology; and history of systemic reactogenicity, COVID-19, interval between doses ≥ 4 weeks and time to serology < 14 weeks were associated with an elevated antibody response. Conclusions: This study provides data on the humoral response to the Sputnik V vaccine in a real-life setting. These initial data can contribute to the development of future immunization strategies in HCWs.

Care pathways models and clinical outcomes in Disorders of consciousness.

OBJECTIVE: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients' clinical outcomes. MATERIALS AND METHODS: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by asking 90 patients' caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received. RESULTS: Seventy-three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diagnosis. In long-term care units, the diagnosis at admission and the number of caregivers available for each patient (median value = 3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non-Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. CONCLUSION: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and actions are needed to guarantee equity and standardization of the care process in all European countries.

Antiretroviral Therapy Containing Raltegravir to Prevent Mother-to-Child Transmission of HIV in Infected Pregnant Women.

We conducted a retrospective study in a general hospital in Buenos Aires, Argentina (2009-2015) aimed at evaluating outcomes in HIV-infected pregnant women (HIPW), who were prescribed raltegravir (RAL)-containing antiretroviral therapy (ART). A total of 239 HIPW were enrolled in our study; among them 31 received RAL (12.9%) at different clinical stages: i) intensification (INS): addition of RAL to current ART because of detectable antepartum viral load, 13 (41.9%); ii) late presenter (LP): standard ART + RAL as fourth drug, 15 (48.4%); iii) treatment of resistant-HIV: 3 (9.7%). Median gestational age at RAL initiation was 34 weeks and median exposure was 30 days. In INS-group, median viral load (VL) decrease was 1.48 log10. In LP-group, median VL decline was 2.15 log10. No clinical adverse events or maternal intolerance attributable to RAL were observed. Elective cesarean section was done in 51.7%; mild elevation of transaminases was observed in 35% of neonates. No vertical transmission was documented.

Severe hypokalemia due to a possible drug-drug interaction between vinblastine and antiretrovirals in a HIV-infected patient with Hodgkin's lymphoma.

A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir. In the subsequent ABVD cycles, no neutropenia or hypokalemia were observed. Vinblastine is metabolized by the hepatic P450 cytochrome isoenzyme CYP3A4, therefore, concomitant administration with protease inhibitors may increase plasma levels of vinblastine. Vinblastine is also a substrate and inhibitor of multidrug resistance-associated protein 2 (MRP2) transporter in the proximal renal tubule. Inhibition of this renal transporter could increase tenofovir renal toxicity. Our hypothesis is that the hypokalemia could be a result of a tenofovir-mediated tubular damage triggered by the increased vinblastine serum levels secondary to a CYP3A4 inhibition by ritonavir. To the best of our knowledge, this is the first report of severe hypokalemia and proximal tubular renal dysfunction as a result of a possible drug-drug interaction between vinblastine, tenofovir and ritonavir-boosted atazanavir.

Possible Drug-Herb Interaction between Herbal Supplement Containing Horsetail ( Equisetum arvense) and Antiretroviral Drugs.

The use of alternative medicines, including herbs, is common among HIV-positive patients, even in those on antiretroviral treatment. Equisetum arvense, known as "horsetail," is mainly used for its diuretic properties. There are limited data about the pharmacological properties of this compound and the potential drug-herb interactions. The authors report 2 cases in which a possible drug-herb interaction may have led to virological breakthrough in patients who were maintained on the same regimen for many years, including lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV) and emtricitabine (FTC)/tenofovir (TDF)/EFV, respectively. Therefore, a drug-herb interaction may be expected when these agents are taken concurrently. Until additional data are available, the authors advise clinicians to avoid this combination when possible.

Sensiblidad antimicrobiana de bacilos gramnegativos de infecciones intraabdominales de la comunidad en un hospital de la ciudad de Buenos Aires, Argentina / Antimicrobial susceptibility of Gram-negative bacilli of community acquired intra-abdominal infections in a hospital at Buenos Aires, Argentina

Introducción. Las infecciones intraabdominales complicadas (IIAC) adquiridas en la comunidad son una patología muy prevalente.Existen pocos datos disponibles en Argentina del nivel de resistencia antimicrobiana de bacilos gramnegativos aislados de IIAs adquiridas en la comunidad. Métodos. Estudio retrospectivo-prospectivo y observacional (marzo 2010 a febrero 2012). Se evaluó la sensiblidad antimicrobiana de bacilos gramnegativos aislados de IIAC de pacientes provenientes de la comunidad. Resultados. Se incluyeron 85 pacientes, de los cuales se aislaron 138 patógenos. Sexo masculino: 58%. Mediana de edad: 33. Se obtuvo aislamiento monomicrobiano en un 49% de los casos. Del total de aislamientos, se aislaron 90 (65%) bacilos gramnegativos y 48 (38%) cocos grampositivos. Las especies de bacilos gramnegativos más frecuentemente observadas fueron: Escherichia coli 76%, Klebsiella pneumoniae 8%, Pseudomona aeruginosa 7% y Enterobacter spp. 6%. E. coli y K. pneumoniae mostraron un elevado porcentaje de cepas resistentes a ciprofloxacino, 37% y 29%, respectivamente. Del mismo modo, la resistencia a ampicilina/sulbactam fue de 16% para E. coli. La frecuencia de bacilos gramnegativos multirresistentes fue de 38%. Conclusiones. Se observó un elevado nivel de resistencia a antimicrobianos en bacilos gramnegativos de IIAC de pacientes provenientes de la comunidad, principalmente a ciprofloxacino y ampicilina/sulbactam. Además se identificó una considerable proporción de bacilos gramnegativos multirresistentes (AU)

Introduction. Community acquired complicated intra-abdominal infections (cIAI) are a common condition. Few data are available about the level of antimicrobial resistance of Gram-negative bacteria isolated from community acquired cIAIs in Argentina. Methods. Retrospective-prospective observational study (March 2010 to February 2012). Gram-negative bacteria antimicrobial susceptibility of isolates from community acquired cIAIs were evaluated. Results. During this period, a total of 85 patients were included and 138 pathogens were collected. Male sex: 58%. Median age: 33. Monomicrobial cultures were obtained in 49% of the cases. Ninety (65%) corresponded to Gram-negative organisms, and 48 (38%) to Gram-positive cocci. Gram-negative organisms most frequently observed were: Escherichia coli 76%, Klebsiella pneumoniae 8%, Pseudomonas aeruginosa 7% and Enterobacter spp. 6%. E. coli and K. pneumoniae showed a high percentage of strains resistance to ciprofloxacin of 37% and 29%, respectively. Similarly, resistance to ampicillin/sulbactam was observed in a 16% of the E. coli isolates. The prevalence of multiresistant Gram-negative organisms was 38%. Conclusions. A high level of resistance to antimicrobials was observed in community acquired cIAIs, mainly to ciprofloxacin and ampicillin/sulbactam two of the most used antimicrobial for empirically treatment of cIAIs in our country. In addition a significant proportion of multiresistant Gram-negative organisms were identified (AU)