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Summary Background Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0–52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31–1·83), men who have sex with men (1·42, 1·09–1·86), and those with four or more chronic comorbidities (1·46, 1·09–1·97). Age at least 75 years (5·2, 1·8–15·3), non-Spanish origin (2·1, 1·3–3·4), and neuropsychiatric (1·69, 1·07–2·69), autoimmune disease (1·92, 1·14–3·23), respiratory disease (1·84, 1·09–3·09), and metabolic disease (2·59, 1·59–4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding Fundacio "la Caixa". Translations For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.

Introduccion Existe poca informacion sobre bacteriemias en pacientes muy ancianos. El objetivo del trabajo fue describir las caracteristicas de estas en esta poblacion. Metodos Estudio prospectivo de las bacteriemias en pacientes mayores de 80 anos y comparacion con pacientes de 18-64 y de 65-79 anos. Resultados Se analizaron 146 bacteriemias en pacientes mayores de 80 anos. En el 66,4% hubo alguna comorbilidad y en el 6,8%, alguna causa de inmunodeficiencia. El 82,2% no tenia enfermedad de base o esta no fue fatal. El origen fue comunitario en 80 casos. Los principales focos fueron: primario (25,3%) y urinario (20,5%); y los aislamientos mas frecuentes: Escherichia coli (28,2%), Staphylococcus coagulasa negativos (14,7%) y Staphylococcus aureus (13,6%). Presentaron sepsis o shock septico el 55,5%, y fallecieron 31 en relacion con la bacteriemia. Los pacientes mayores de 80 anos tuvieron menos frecuencia de inmunodeficiencia y mayor proporcion de infecciones comunitarias y por gramnegativos. La mortalidad relacionada con la bacteriemia fue mayor en el grupo de mas edad y se asocio con la presencia de una enfermedad de base fatal o finalmente fatal, la bacteriemia por S. aureus y con el inicio de un tratamiento empirico inapropiado. Un indice de gravedad de Pitt mas bajo se mostro como una variable protectora. Conclusiones Los pacientes muy ancianos con bacteriemia tienden a presentar menos causas de inmunodeficiencia, mayor frecuencia de infecciones comunitarias y por germenes gramnegativos. Existe mayor riesgo de mortalidad relacionada, sobre todo en presencia de enfermedad de base, bacteriemia por S. aureus o tras un tratamiento empirico inapropiado.

The aim of this study was to analyse factors associated with progression to AIDS/death in severely immunosuppressed HIV-infected patients receiving ART.This study included naive patients from the PISCIS Cohort with CD4200 cells/mm(3) at enrolment and who initiated ART consisting of two nucleoside analogues plus either a PI or an NNRTI between 1998 and 2011. The PISCIS Cohort is a multicentre, observational study of HIV-infected individuals aged18 years followed at 14 participating hospitals in Catalonia and the Balearic Islands (Spain). Clinical and laboratory parameters were assessed every 3-4 months during follow-up. Cox regression models were used to assess the effect of CD4 and viral load on the risk of progression to AIDS/death, adjusting for baseline variables and confounders.2295 patients were included and, after 5 years, 69.9% reached CD4 ≥200 cells/mm(3), 64.4% had an undetectable viral load and 482 (21%) progressed to AIDS/death. The lowest rate of disease progression was found in patients who reached both immunological and viral responses during follow-up, regardless of their baseline situation (1.9% in baseline CD4100 cells/mm(3) and viral load5 log copies/mL; 2.3% in baseline CD4 ≤100 cells/mm(3) and/or viral load5 log copies/mL). Achieving a CD4 count ≥200 cells/mm(3) was the main predictor of decreased progression to AIDS/death. In those not reaching this CD4 threshold, virological response reduced disease progression by half.Even in the worse baseline scenario of CD4 ≤100 cells/mm(3) and high baseline viral loads, positive virological and immunological responses were associated with dramatic decreases in progression.

The combination of indinavir, a protease inhibitor, and reverse-transcriptase inhibitors is widely used in the treatment of HIV-1 infection. However, precipitation of indinavir crystals in the renal tubular lumen due to the drug's aqueous insolubility may result in characteristic symptoms of flank pain or classic renal colic. An in vitro study has shown that addition of escin to synthetic urine containing indinavir delayed the crystallization time of indinavir.This study examined the efficacy and tolerability of the addition of escin to highly active antiretroviral therapy containing indinavir to delay the crystallization time of indinavir in urine.This was a multicenter, randomized, open-label, controlled, 4-period crossover trial in which each period lasted 4 weeks. HIV-1-infected adults receiving treatment with indinavir plus 2 nucleoside analogue reverse-transcriptase inhibitors in whom plasma viral loads had been undetectable (HIV-1 RNA200 copies/mL) for at least 6 months were randomly assigned to 1 of 2 groups based on the timing of the initiation of escin. Group I received escin during the second and third treatment periods, and group II received escin during the first and fourth treatment periods. The primary end point was the in vitro crystallization time of indinavir in 24-hour urine specimens, determined at the end of each 4-week period. Tolerability was assessed based on the number of patients with a rebound in plasma viral load and on the numbers of clinically and biologically relevant adverse events (including those requiring discontinuation of treatment). Clinical and laboratory evaluations were performed throughout each 4-week period.Fifty HIV-1-infected patients were enrolled, 47 were randomized to treatment (40 [85.1%] men, 7 [14.9%] women; median [interquartile range] age, 36 [34-45] years), and 30 completed the study. Urine pH and plasma and urine indinavir concentrations were unaffected by the addition of escin to antiretroviral treatment. The mean time to the onset of crystallization was 14.7 minutes with escin (95% Cl, 11.8-17.5) and 9.9 minutes without it (95% Cl, 6.7-13.1). Therefore, the addition of escin increased the mean crystallization time by 5.5 minutes (95% Cl, 1.5-9.5; P = 0.008), representing the overall capacity of study treatment to inhibit indinavir crystallization in the urine. Three of 47 patients had mild gastrointestinal symptoms associated with escin treatment. No episodes of nephrolithiasis were recorded during the study or after the completion of study treatment.The results of this prospective clinical trial of the effect of escin on indinavir crystallization time support the possibility that indinavir-associated nephrolithiasis may be prevented by means other than overhydration. Further research is needed in greater numbers of patients over longer follow-up times.