Alexandre Naime Barbosa

Antiretroviral therapy (ART) has transformed HIV from a life-limiting infection into a manageable chronic condition, shifting attention toward the emerging challenges faced by the growing population of adults aged 50 years or older living with HIV. This observational cohort study tracked 1,018 individuals treated in the medical system in Brazil, a middle-income country, to better understand the effectiveness of traditional and simplified ART regimens in older adults living with HIV (OALH), a frequently underrepresented group in clinical studies. Older adults, those aged 50 and above, living with HIV achieved significantly higher rates of undetectable viral load (89.4 vs 83.2%, P500 copies/mL (2.5 vs 10.1%; P<0.0001) than younger adults aged 18-49, and demonstrated superior immune recovery through significantly greater CD4+ T-cell counts (P=0.0012). The multivariate analysis found that improved clinical outcomes (undetectable viral load) were most highly correlated with the simplified treatment regime and more years of treatment duration. These findings highlight the value of simplified ART regimens and sustained treatment duration, which were observed to be more frequent in OALH.

Rhodococcus equi, a versatile and adapted opportunistic in nature bacterium, infects animals and humans. This soil-borne microorganism widely occurs in farms. Its dissemination occurs by feces from domestic animals (particularly horses, cattle, and pigs). In the last decades, bacterial virulence has been strongly attributed to plasmid-encoded virulence-associated proteins (VAPs). To date, three virulence plasmid types have been recognized: pVAPA, pVAPB, and pVAPN, which are considered host- or livestock-adapted. The pVAPA type is related to equine isolates (horse-type), the pVAPB type is associated with pig isolates (porcine-type), whereas the pVAPN type occurs in domestic ruminants (bovine and caprine) (ruminant-type). Nonetheless, pathogenic R. equi possessing the three virulent plasmid types can infect humans. Inhaling aerosol particles from the environment of equids represents the first route traditionally considered for the transmission of R. equi to humans, although an epidemiological lack of transmission remains in human infections because some patients with rhodococcosis have no history of contact with livestock or their environment on farms. However, all pVAPs types have been found in humans infected by R. equi (predominantly living with HIV), which could be presumably transmitted to patients by the ingestion of contaminated undercooked or raw meat from slaughtered pigs, cattle and, occasionally, horses, representing a probably route of the transmission of the pathogen from livestock-to-humans that could partially explain infections in humans without a history of contact with cattle, pigs, horses, or their farm environments.

Objective: Nucleoside/nucleotide reverse transcriptase inhibitors, particularly tenofovir, can cause long-term side effects such as decreased bone mineral density and estimated glomerular filtration rate. A strategy to mitigate these effects is the simplification of antiretroviral therapy, which involves withdrawing one of the nucleoside/nucleotide reverse transcriptase inhibitors from the therapeutic scheme. While clinical trials and real-world studies have demonstrated that the simplified therapy maintains undetectable viral loads, its impact on bone mineral density and kidney function remains unclear owing to the lack of real-world evidence. Methods: This retrospective cohort study compared 152 patients who underwent antiretroviral therapy simplification (primarily due to osteopenia, osteoporosis, or decreased estimated glomerular filtration rate) with 306 patients who maintained triple therapy, between April 2013 and September 2022. The simplified regimens included lamivudine plus dolutegravir or ritonavir-boosted darunavir. The groups were analyzed based on their demographic characteristics using Student’s t-test in the case of symmetric data. Therapeutic success (undetectable viral load at the end of follow-up) was assessed using Kaplan Meier survival analysis . The estimated glomerular filtration rate variation before and after simplification was analyzed using the Mann-Whitney test . Pre-and post-simplification bone mineral density values were evaluated using the chi-square test for trends and assessed in the simplified therapy group. A significance level of 5% (α = 0.05) was adopted for all tests. Results: Simplified antiretroviral therapy was non-inferior to triple therapy in maintaining undetectable viral load. Patients receiving simplified regimens showed a positive variation in estimated glomerular filtration rate. A small subset of patients also exhibited improvements in bone mineral density after antiretroviral therapy simplification. Conclusions: These findings suggest that simplified therapy is as effective as triple therapy and has the additional benefit of reducing tenofovir-related adverse events.

O interesse pelo estudo das zoonoses, enfermidades comuns aos humanos e aos animais e relacionados à saúde única, aumentou acentuadamente nos últimos anos, exigindo maior integração, conhecimento e relacionamento entre profissionais da área da saúde. A toxoplasmose e a doença de Chagas (DC) têm elevada importância para a saúde pública, especialmente para as pessoas vivendo com HIV/Aids (PVHA), pois a imunossupressão pode agravar a doença. O estudo teve como objetivo determinar a prevalência destas zoonoses em PVHA atendidos no Serviço de Ambulatório Especializado de Infectologia “Domingos Alves Meira” (SAEI-DAM), da Faculdade de Medicina de Botucatu, Unesp, e sua associação com fatores de risco relacionados a ambos. Pesquisou-se anticorpos para Toxoplasma gondii e Trypanosoma cruzi em 236 amostras de soro de PVHA, 154 (65%) resultaram positivas para T. gondii e 4 (1,69%) para T. cruzi. Vinte e um pacientes (8,89%) apresentaram neurotoxoplasmose e seis (2,54%) toxoplasmose ocular. A elevada soroprevalência para toxoplasmose pode ser por consequência da estreita interação com os animais de estimação, principalmente gatos, entre outros fatores, concluindo que o risco de toxoplasmose clínica é alto na população estudada pela possibilidade da reativação em pacientes imunocomprometidos, agravado pela desinformação sobre as formas de infecção e uso irregular da TARV constatada na pesquisa. Diante dos resultados, acredita-se que o acesso à informação, especialmente naqueles procedentes da zona rural, seja uma medida de grande efetividade na prevenção da exposição à toxoplasmose, já que a maior soropositividade esteve associada aos indivíduos com menor escolaridade e a hábitos alimentares associados à procedência dos produtos de origem animal (carne e leite) e ingestão de água de torneira. Campanhas educativas que promovam o desenvolvimento de atitudes e estilo de vida podem proporcionar redução na morbimortalidade nesta população de risco.

Objective: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. Methods: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. Results: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = -0.21 (95% CI, -0.34 to -0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. Conclusions: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

The coronavirus disease 2019 (COVID-19) pandemic has had a direct impact on health care systems worldwide. By February 1, 2023, more than 753 million people had been infected with the virus, and more than 6.8 million deaths had occurred¹ 1. World Health Organization. Report of the WHO global situation. [cited on Feb 22, 2023] Available from: Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports https://www.who.int/emergencies/diseases... . These death rates are related to the spread of the virus and are currently more common in places where vaccination rates are low. The worldwide incidence still fluctuates, with over 5 million cases per week. Failure to control viral transmission facilitates the occurrence of new mutations and immune escape, which may determine the persistence of the disease for a much longer period than expected¹ 1. World Health Organization. Report of the WHO global situation. [cited on Feb 22, 2023] Available from: Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports https://www.who.int/emergencies/diseases... .

Background: In the absence of direct therapy for COVID-19, extracorporeal blood treatment (EBT) could represent an option for cytokine removal. Objective: This study aimed to describe and compare cytokine removal during intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT) in COVID-19 patients with Acute Kidney Injury (AKI). Methods: It was a cohort study that studied patients with COVID-19-related AKI according to KDIGO criteria and admitted at Intensive Care Unit (ICU). Blood samples were collected at the start and end of both IHD using high flux (HF) membranes (10 patients) and continuous venovenous haemodiafiltration (CVVHDF:10 patients) in two sessions for measuring 13 different plasma interleukins and calculating the cytokine removal rate. Results: There was no difference between the two groups regarding mechanical ventilation, vasoactive drug, age or prognostic scores. Patients treated by CRRT presented higher levels of IL-2 and IL-8 than patients treated by IHD at dialysis start. Cytokine removal ranged from 9% to 78%. Patients treated by CRRT presented higher cytokine removal for IL-2, IL-6 IL-8, IP-10 and TNF. The removal rates of IL-4, IL-10, IL-17A, IFN, MCP-1 and TGF-B1 were similar in two groups. After one session of CVVHDF (24 h), IL-2 and IL-1β levels did not vary significantly, whereas IL-4, IL-6, IL-8, IL-10, IL-17A, TNF, IFN, IP-10, MCP-1, IL-12p70 and TGF-B1 decreased by 33.8– 76%, and this decrease was maintained over the next 24 h. In IHD groups, IL-2, IL-6, TNF, IP-10 and IL-1β levels did not decrease significantly whereas IL-4, IL-8, IL-10, IL-17A, IFN, MCP-1, IL-12p70 and TGF-B1 decreased by 21.8– 72%; however, cytokine levels returned to their initial values after 24 h. Conclusion: Cytokine removal is lower in IHD using HF membranes than in CVVHDF, and in IHD the removal is transient and selective, which can be associated with mortality during cytokines storm-related COVID-19.

Objective: To answer questions related to the use of anticoagulants in the treatment of COVID-19 patients. Methods: This was a systematic review and meta-analysis of phase 3 randomized controlled trials comparing the use of anticoagulants in non-hospitalized and hospitalized COVID-19 patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to January 22, 2022. The risk of bias was assessed by the Cochrane risk-of-bias tool, and the quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation system. Results: A total of 401 studies were initially selected. Of those, 9 met the inclusion criteria and were therefore analyzed (a total of 6,004 patients being analyzed). In non-hospitalized COVID-19 patients, no significant difference was found between post-discharge prophylactic anticoagulation and no intervention regarding venous thromboembolism or bleeding at 30 days. In hospitalized COVID-19 patients, full anticoagulation resulted in a slight reduction in thrombotic events at 30 days (risk difference, -0.03; 95% CI, -0.06 to -0.00; p = 0.04; I2 = 78%), the quality of evidence being moderate. However, no significant difference was found between full anticoagulation and no intervention regarding the risk of major bleeding, the quality of evidence being very low. No significant difference was found between intermediate- and standard-dose prophylactic anticoagulation (risk difference, -0.01; 95% CI, -0.07 to 0.06; p = 0.81; I2 = 0%), the quality of evidence being very low. Conclusions: Therapeutic anticoagulation appears to have no effect on mortality in COVID-19 patients, resulting in a slight reduction in venous thromboembolism in hospitalized patients.