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BackgroundIt is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.MethodsNon-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.FindingsParticipants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Introdução: Estima-se que 1/4 da população mundial esteja infectada com Mycobacterium tuberculosis, com maior risco de doença concentrado nos primeiros anos após a infecção primária, porém o período de latência pode durar anos. Tanto a infecção pelo HIV como o envelhecimento são fatores de risco para tuberculose ativa(Tb). No entanto, existe uma lacuna na compreensão do risco de Tb na população de pessoas idosas que vivem com HIV(PIVHA). Objetivo: Avaliar a prevalência de infecção latente por tuberculose(ILTB) em PIVHA e fatores associados. Método: Estudo incluiu PIVHA (≥ 50 anos) em terapia antirretroviral em quatro centros de 3 cidades brasileiras. Exames laboratoriais, incluindo IGRA (Interferon-gama release assay) para ILTB foram realizados. Aqueles com história documentada de tuberculose ativa/tratada ou com resultado de IGRA ausente/inconclusivo foram excluídos. ILTB foi definida por IGRA positivo no baseline ou IGRA ou PPD(prova tuberculínica) previamente positivo. As razões de prevalência de ILTB foram avaliadas por modelos de regressão de Poisson modificados não ajustados e multivariados, considerando covariáveis como idade, sexo ao nascer, raça, anos de diagnóstico de HIV, cidade de residência, escolaridade, renda, insegurança alimentar, uso atual de álcool/substâncias/tabaco e contagem de células TCD4 no baseline. Resultados: Excluidos 158 participantes por histórico de Tb ativa e 72 por resultados testes de ILTB ausentes/inconclusivos. 473 PIVHA foram incluídos na análise. Idade média de 62 anos; 293 (62%) sexo masculino ao nascer; 129 (29%) pardos e 101 (21%) negros. A mediana de anos de diagnóstico de HIV foi de 23; mediana do número de residentes no domicílio foi 2; 110 (23%) relataram renda familiar mensal < 1 salário mínimo; 95 (20%) tinham < 8 anos de escolaridade; e a mediana da contagem de células TCD4 foi de 752 células/μL. A prevalência de ILTB foi de 169/473 (36%), variando entre as cidades (44% Rio de Janeiro, 38% São Paulo e 23% Salvador). Na análise multivariada, contagem de células TCD4 (< 500 vs. ≥ 900 aPR:0,64 [IC95% 0,45-0,93]) e renda (< 1 vs 1-3 salários mínimos aPR:1,53 [IC95% 1,09-3.14]) foram associados ao risco de ILTB. Conclusão: Encontramos elevada prevalência de ILTB em PIVHA, particularmente associada à contagem de células TCD4 e baixa renda. Estes dados evidenciam a urgência de iniciativas para aumentar o acesso a testes de diagnóstico de ILTB e ao seu tratamento para reduzir o risco de doença e morte por tuberculose nesta população.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Abstract Environmental factors favoring myopia development are still being studied and there is accumulating evidence for a significant role of nearwork. Recently, reading standard black-on-white text was found to activate the retinal OFF pathway and induce choroidal thinning, which is associated with myopia onset. Contrarily, reading white-on-black text led to thicker choroids, being protective against myopia. Respective effects on retinal processing are yet unknown. Here, we exploratively assessed the impact of contrast polarity on the retinal activity and possible interactions with eccentricity and refractive error. We recorded pattern electroretinograms in myopic and emmetropic adults while presenting a dead leaves stimulus (DLS), overlaid by masks of different size in ring or circle shape, either filled with uniform gray or text of inverted or standard contrast. In myopes, retinal responses for DLS with standard and inverted contrast were larger when the perifovea was stimulated (6–12 deg), however, including the fovea resulted in smaller amplitudes for inverted contrast than in emmetropes. The retina of emmetropes was more sensitive to inverted contrast than to standard and gray within 12 deg, but most sensitive for gray in the perifovea. This demonstrates that the refractive error influences the sensitivity to text contrast polarity, with a special role of the peripheral retina, which is in line with previous studies about blur sensitivity. Defining whether the differences derive from retinal processing or anatomical features of a myopic eye requires further investigation. Our approach might be a first step to explain how nearwork promotes the eye’s elongation.

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity.

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count 3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

ABSTRACT COVID-19 has challenged the scientific community in the search for biological markers and information that can contribute to the early management of the severe disease. Given the global scale of COVID-19, including reports of reinfection even in the presence of effective vaccines; consequently, the eradication of SARS-CoV-2 is far from happening. This study aimed to characterize the neutralizing antibody (Nab) geometric mean titers (GMTs) in hospitalized patients with COVID-19 and to evaluate the association with length of stay, comorbidities, and patient outcome. Among the 103 participants, 84 (81.5%) had some previous conditions associated with worsening health and 34 (33%) died. We found that neutralization potency varied greatly across individuals and was significantly higher in patients discharged before 14 days than in patients who stayed longer in the hospital. During the study period, 15 people living with HIV (PLWH) were hospitalized, and no significant difference in clinical characteristics or anti-SARS-CoV-2 Nabs was observed. However, PLWH with severe COVID-19 were younger [42, interquartile range (IQR) = 17.5] than other hospitalized COVID-19 patients (59, IQR = 22, P < 0.01). A high anti-HIV-1 antibody GMT of 583.9 (95% confidence interval: 344–990) was detected, demonstrating maintenance of anti-HIV-1 Nab production among PLWH coinfected with SARS-CoV-2. Therefore, these results indicate that neutralizing antibodies are not the only immunological response capable of controlling disease progression, but a high neutralizing response was associated with a shorter length of stay, suggesting the benefit of early-stage immunotherapy treatment of COVID-19. Nevertheless, these data highlight the importance of more Nab screening studies to predict faster recovery. IMPORTANCE The study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches.

Background: Cisgender men were mostly affected during the 2022 mpox multinational outbreak, with few cases reported in women. This study compares the characteristics of individuals diagnosed with mpox infection according to gender in Rio de Janeiro. Methods: We obtained surveillance data of mpox cases notified to Rio de Janeiro State Health Department (June 12 to December 15, 2022). We compared women (cisgender or transgender) to men (cisgender or transgender) using chi-squared, Fisher's exact, and Mood's median tests. Results: A total of 1306 mpox cases were reported; 1188 (91.0%) men (99.8% cisgender, 0.2% transgender), 108 (8.3%) women (87.0% cisgender, 13.0% transgender), and 10 (0.8%) non-binary persons. Compared to men, women were more frequently older (40+years: 34.3% vs. 25.1%; p

Introdução/Objetivo: A América Latina tem observado um aumento alarmante nas novas infecções pelo HIV entre jovens gays e outros homens que fazem sexo com homens (HSH). No Brasil, houve um aumento expressivo no número de casos de HIV entre pessoas do sexo masculino até 30 anos, mas dados específicos sobre jovens HSH ainda são escassos. Neste trabalho, objetivamos estimar a prevalência de infecções por HIV e outras infecções sexualmente transmissíveis (ISTs) em jovens HSH do Rio de Janeiro. Métodos: Conectad@s é um estudo com amostragem por respondent-driven sampling (RDS), que recrutou jovens HSH de 18-24 anos entre novembro/2021 e outubro/2022. Os participantes realizaram testagem para HIV, sífilis, clamídia e gonorreia (urina, retal e orofaringe), e responderam questionários estruturados sobre aspectos comportamentais e de saúde. Foram avaliados os fatores associados a novas infecções pelo HIV utilizando teste qui-quadrado e de Fisher. Resultados: Foram recrutados 409 jovens HSH, dos quais 370 (90,5%) eram homens cis, 9 (2,2%) homens trans e 30 (7,3%) pessoas não-binárias/queer, com idade média de 21 anos (intervalo interquartil: 20-23). Ao todo, 70,3% (n = 291) se autodeclararam Pretos, Pardos ou Indígenas, e 60,4% (n = 247) tinham ensino médio completo. A prevalência de HIV foi 9,8% (n = 40/409). Dentre os indivíduos vivendo com HIV, 50,0% (n = 20) eram novos diagnósticos. No geral, 54 (13,2%) e 47 (11,5%) indivíduos, respectivamente, testaram positivo para clamídia e gonorreia em pelo menos um dos três locais de coleta. Comparados aos participantes HIV-negativos, os recém-diagnosticados com HIV mais frequentemente reportaram raça/cor Preta/Parda/Indígena (90,0% vs. 69,6%), ter estudado até o ensino médio (80,0% vs. 59,3%), maior número de parcerias sexuais (mediana 9[IQR:5.8-20] vs. 5[IQR:3-10], p-valor < 0.01), maior risco para HIV (60,0% vs. 24,9%, p-valor < 0.001), menor conhecimento sobre o HIV (escala 0-12 pontos; mediana 9,5[IQR:8-11] vs. 11[IQR:9-11], p-valor < 0.05), e maior prevalência de sífilis ativa (50,0% vs. 10,8%, p-valor < 0.001), clamídia (25,0% vs. 14,6%), e gonorreia (45,0% vs. 13,6%), esses últimos em pelo menos um dos locais de coleta. Conclusão: Jovens HSH apresentaram alta vulnerabilidade e taxas desproporcionais de novos diagnósticos de HIV e outras ISTs, apontando para oportunidades de prevenção perdidas. Há uma necessidade urgente de adaptar intervenções específicas e eficazes para alcançar e promover a prevenção ao HIV entre jovens HSH.

Introdução: O diagnóstico de IVA pelo HIV exige alta suspeição, devido ao período de soroconversão, sendo necessários exames de 4ª geração ou carga viral em indivíduos com quadro clínico sugestivo ou exposição sexual recente, sobretudo no contexto de início de PrEP ou PEP. O início precoce da terapia antirretroviral (TAR) em pessoas com IVA pode reduzir reservatórios virais, sendo de potencial interesse em pesquisas de cura funcional. Nosso trabalho objetiva descrever o perfil de indivíduos com IVA acompanhados no Rio de Janeiro, Brasil. Métodos: Coorte prospectiva, incluiu sequencialmente pessoas ≥ 18 anos diagnosticadas com IVA pelo HIV de 2013-2023 acompanhadas em centro no Rio de Janeiro, Brasil. Foram coletados dados sociodemográficos, clínicos, comportamentais e laboratoriais. Realizamos uma análise descritiva das características no atendimento inicial. Participantes foram submetidos a TCLE e o projeto foi submetido ao Comitê de Ética em Pesquisa local. Resultados: Dos 103 participantes, 91% eram homens cis (96% HSH, n = 89/93), 7% travestis/mulheres trans (TMT), 1% não binárie e 1% mulher cis, majoritariamente com idade < 30 anos (65%), autodeclarados pretos/pardos (59%) e de escolaridade pós-secundária (58%). Enquanto 58% apresentaram síndrome retroviral aguda, o diagnóstico de IVA ocorreu no acompanhamento de PrEP/PEP em 34%. A mediana de log de carga viral HIV pré-tratamento foi 4.7, com CD4 de 577 cél/mm3, sendo 74% com CD4/CD8

Introdução: A infecção por S. aureus está associada a alta morbi-mortalidade. Métodos: Estudo de coorte retrospectivo descrevendo infecção grave por S.aureus em pacientes internados de 2016 a 2021. Realizada busca nos registros de microbiologia e revisão de prontuários para coleta de dados. Análise estatística com R 4.0.1 Resultados: Foram incluídos 67 pacientes, que apresentavam os seguintes sítios de infecção: 29 (43.3%) bacteremia e 38 infecções em outros sítios (lesão cutânea, pulmonar e outros). Eram homens 37 (55,2%); 69.4% negros, com idade mediana de 46 anos (IIQ = 31). As comorbidades mais frequentes em pessoas com infecção por S.aureus foram: Diabetes Mellitus (DM 17.9%), Hipertensão (13.4%), Doença Renal Crônica (DRC 11.9%), Câncer Recente (isto é, nos últimos 6 meses (CA 7.5%), Dermatopatia crônica (9%), e HTLV (9%), e pessoas vivendo com HIV/AIDS (PVHIV) 31(46,3%). Os PVHIV eram mais jovens que os não portadores do vírus (36 vs 60 anos, p < 0,001). A mediana do CD4 foi de 95 células/mm3, e 25/31 (75.8%) das PVHIV estavam em uso de terapia antirretroviral (TARV). Identificou- se que nos PVHIV, 7 (22%) já apresentavam-se colonizados por MRSA na admissão e que 20 (64%) PVHIV tinha infecção comunitária por S.aureus. Nos PVHIV afigurou- se uma prevalência de 38.7% de infecções por MRSA e destes, 100% era sensível a sulfametoxazol-trimetoprima (SXT), à doxiciclina e à linezolida; e 90% a clindamicina, mostrando-se fenotipicamente com padrão de MRSA comunitário. Internação em CTI ocorreu em 32.3% das PVHIV vs 50% (p = 0.22) dos soronegativos, e cerca de 1/3 das PVHIV e das soronegativas necessitou de suporte ventilatório de aminas e de HD. Registrou-se 25.8% de óbitos em 30 dias para os PVHIV vs 20% naqueles soronegativos para HIV (p = 0.789). Conclusão: Nosso estudo mostrou alta taxa de colonização por MRSA (38.7%) em PVHIV com infecção grave por S.aureus, maior que a descrita na população geral sem infecção por S.aureus (0.3% a 1.3%) e nos profissionais de saúde (1.3 a 2.3%). As comorbidades na população geral do estudo se assemelha àquelas descritas em outros estudos, como HIV, DM, Ca recente e condições que predispõem quebra de integridade cutânea – DRC. Observamos uma população mais jovem com S.aureus e HIV comparando com os soronegativos. Em consonância com a literatura, que coloca CD4

Introdução: A incorporação da PrEP como política de saúde pública ampliou a testagem de IST no Brasil. O país é um dos mais afetados pela sífilis a nível global, no entanto carece de dados populacionais sobre clamídia (CT) e gonorreia (NG). O ImPrEP foi um estudo que avaliou a implementação da PrEP no Brasil, México e Peru. No Brasil, incluiu 3.928 HSH e TMT. O objetivo desse trabalho é explorar dados relacionados às vulnerabilidades para IST no Brasil entre participantes acompanhados no ImPrEP. Métodos: De 2018 a 2020, incluímos HSH e TMT ≥ 18 anos, com seguimento até 2021. Exames para IST bacterianas foram coletados na inclusão e trimestralmente (sífilis) ou anualmente (CT/NG). Consideramos todos os participantes do ImPrEP no Brasil com realização de pelo menos um exame para qualquer IST bacteriana (sífilis, CT/NG) durante o estudo. Realizamos análise descritiva das frequências de IST por unidade federativa (UF) e das características sociodemográficas e comportamentais dos participantes. Resultados: Incluímos 3.478 participantes de 8 UF de todas as regiões do país, com maior concentração no Rio de Janeiro (RJ) (30%) e São Paulo (SP) (27%). Desses, 25% tinham 18-24 anos, 51% eram não brancos, 80% com escolaridade pós-secundária, 96% HSH e 4% TMT. Na inclusão, a prevalência de sífilis foi maior no Distrito Federal (DF) (17%) e no Amazonas (AM) (15.6%), enquanto CT/NG não apresentaram diferenças significativas entre UF. Maior incidência de sífilis foi identificada em Santa Catarina (SC) (15.8/100 pessoas-ano), DF (14.8/100 pessoas-ano) e Bahia (BA) (13.5/100 pessoas-ano). Após iniciar PrEP, 35% dos participantes foram diagnosticados com alguma IST bacteriana, sem associação com a UF de origem. Em SC, participantes reportaram mais frequentemente múltiplas parcerias sexuais (53%), no entanto menos relações anais receptivas sem uso de preservativo (39%). O uso excessivo de álcool foi mais frequente em AM (82%) e BA (80%), enquanto o uso de drogas estimulantes ocorreu mais no DF (35%), SP (24%) e RJ (18%). Conclusão: Nossos achados contribuem para caracterização da prevalência de IST entre usuários de PrEP de diferentes estados brasileiros, trazendo dados inéditos sobre infecção por CT/NG nessa população. Considerando a diversidade territorial e cultural do Brasil, vulnerabilidades distintas podem estar envolvidas na dinâmica de transmissão de IST, e a implementação de políticas públicas de prevenção para o HIV e IST deve ser adaptada às realidades locais.

Introdução/objetivo: O Brasil foi o segundo país mais afetado pelo surto de mpox em 2022, com maior frequência de casos entre homens cisgêneros que fazem sexo com homens. Neste surto, observou-se predomínio de lesões mucocutâneas-anogenitais e baixa letalidade (0,15%). Cerca de 38-50% dos casos ocorreram em pessoas vivendo com HIV(PVHA). A imunossupressão pelo HIV pode impactar na gravidade e na duração do quadro de mpox, o que determina a duração do isolamento. Esse estudo objetiva identificar fatores associados ao tempo até resolução das lesões entre pessoas diagnosticadas com mpox no Rio de Janeiro, Brasil. Métodos: Coorte prospectiva de casos confirmados de mpox acompanhados em centro de referência no Rio de Janeiro (jun-2022 a fev-2023). Os perfis sociodemográfico e clínico foram descritos de acordo com o status sorológico para o HIV e o grau de imunossupressão. As variáveis associadas à resolução das lesões foram identificadas por meio de modelos quartis univariados (T = 75%). Resultados: Foram acompanhados 236 casos de mpox até resolução das lesões, entre os quais 49,6% eram PVHA. PVHA reportaram menos relações sexuais 30 dias anteriores(87.3% vs 93.2%), apresentaram mais frequentemente úlceras anais (49.6% vs 23.7%) e genitais (83.8% vs 73.1%), proctite (31.6% vs 17.6%) e coinfecção com outras ISTs (42.7% vs 23.4%). A mediana de tempo até resolução das lesões foi de 24 dias, sem diferença de acordo com status para HIV (p = 0.28). PVHA com imunossupressão severa (CD4+ < 200 céls/mm3) apresentaram maior tempo para resolução das lesões quando comparadas a PVHA com CD4>200céls/mm3 e pessoas negativas para HIV, diferindo em até 79 dias (p < 0,001). Independentemente do status de HIV, infecção bacteriana secundária e acometimento de tecidos profundos estiveram associados a maior tempo de resolução das lesões de mpox, acrescentando 20 dias (p = 0.05) e 76 dias (p < 0.001), respectivamente. Conclusão: Nossos achados indicam a imunossupressão avançada pelo HIV como fator associado a cursos clínicos da mpox mais longos, podendo estender o período de transmissibilidade viral, refletindo no tempo de isolamento. Isso pode agravar questões biopsicossociais, impactando na qualidade de vida do paciente e nas medidas de saúde pública. PVHA e com imunossupressão mais severa apresentam maior vulnerabilidade na evolução da mpox, devendo ser priorizados nas estratégias profiláticas e terapêuticas.

BackgroundThe 2022 multicountry mpox outbreak positioned the condition as a public health emergency of international concern. By May 2023, Brazil ranked second globally in the cumulative number of mpox cases and deaths. The higher incidence of mpox among gay and other men who have sex with men in the current mpox outbreak deepens the stigma and discrimination against sexual and gender minorities (SGM). This might worsen the structural barriers impacting access to health services, which ultimately leads to undertesting and underreporting of cases. There are no data available on mpox knowledge and stigma in Latin America. ObjectiveWe aimed to evaluate mpox knowledge, stigma, and willingness to vaccinate for mpox among SGM, and to describe sociodemographic and behavioral characteristics according to self-reported mpox diagnosis. MethodsA cross-sectional, internet-based survey was conducted in a convenience sample of adults (aged >18 years) living in Brazil recruited through advertisements on dating apps, social media, referral institutions for infectious diseases websites, and mass media (October-November 2022). We compared participants’ characteristics according to self-reported mpox diagnosis using chi-square test or Fisher exact test for qualitative variables and Kruskal-Wallis test for quantitative variables. ResultsWe enrolled 6236 participants: 5685 (91.2%) were cisgender men; 6032 (96.7%) were gay, bisexual, or pansexual; 3877 (62.2%) were White; 4902 (78.7%) had tertiary education; and 4070 (65.2%) reported low or middle income. Most participants (n=5258, 84.4%) agreed or strongly agreed that “LGBTQIA+ individuals are being discriminated and stigmatized due to mpox.” Mpox awareness was 96.9% (n=6044), and 5008 (95.1%) were willing to get vaccinated for mpox. Overall, 324 (5.2%) reported an mpox diagnosis. Among these, 318 (98.1%) reported lesions, 178 (56%) local pain, and 316 (99.4%) sought health care. Among participants not reporting a diagnosis, 288 (4.9%) had a suspicious lesion, but only 158 (54.9%) of these had sought health care. Compared to participants with no diagnosis, those reporting an mpox diagnosis were younger (P

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

Introduction: We aimed to evaluate daily oral pre-exposure prophylaxis (PrEP) uptake, retention, and adherence and predictors of study non-attendance and low PrEP adherence in a Brazilian trans-specific 48-week study (PrEParadas). Methods: We enrolled transgender women (TGW) engaging in high-risk sexual behaviours between August 2017 and December 2018. PrEP adherence was based on tenofovir diphosphate concentrations in dried blood spots (DBS). We used random effects logistic regression models and ordinal models to estimate the odds of having a missed visit and of low PrEP adherence, respectively. Multivariable models were adjusted for variables with p-value Results: From the 271 eligible, 130 participants were enrolled in the study (PrEP uptake: 48%), out of which 111 (85.4%) were retained at 48 weeks. Multivariable model for study non-attendance included study visit, age, main sexual partner and stimulant use. The odds of missing a visit increased after the week 24. Participants aged 18-24 (adjusted odds ratio [aOR] = 8.76, 95% CI: 2.09-36.7) and 25-34 years (aOR = 6.79, 95% CI: 1.72-26.8) compared to TGW aged 35+ years had significantly higher odds of having a missed visit. The odds of a missed visit were higher among participants reporting stimulant use (aOR = 4.99, 95% CI: 1.37-18.1) compared to no stimulant use. DBS levels at week 48 showed that 42 (38.5%), 14 (12.8%) and 53 (48.6%) of 109 participants had low, moderate and high PrEP adherence. Multivariable model for low PrEP adherence included study visit, age, schooling, race/colour, housing, binge drinking, stimulant use, feminizing hormone therapy (FHT) use and received text message. Low PrEP adherence was significantly higher among participants with less years of schooling (aOR = 6.71, 95% CI: 1.30-34.5) and had a borderline association with Black colour/race (aOR = 6.72, 95% CI: 0.94-47.8). Participants using the FHT available at the site had decreased odds of low PrEP adherence (aOR = 0.38, 95% CI: 0.16-0.88). No participant seroconverted over the course of the study. Conclusions: Although high PrEP retention can be achieved in a gender-affirming setting, PrEP adherence may be an important challenge faced among TGW due to social disparities. The scale-up of prevention tools like PrEP will have to address systemic social determinants as these stand as important barriers for TGW's access to health services. Keywords: adherence; HIV; hormones; PrEP; prevention; transgender women, 1 | INTRODUCTION In countries with concentrated epidemics, transgender women (TGW) bear one of the highest burdens of HIV among all population groups. HIV prevalence among TGW in low- and [...]

Abstract HIV controllers (HICs) are models of HIV functional cure, although some studies have shown persistent inflammation and increased rates of atherosclerosis in HICs. Since immune activation/inflammation contributes to the pathogenesis of cardiovascular diseases (CVD), we evaluated clinical data and inflammation markers in HIV-1 viremic controllers (VC), elite controllers (EC), and control groups (HIV positive individuals with virological suppression by antiretroviral therapy—cART; HIV negative individuals—HIVneg) to assess whether they presented elevated levels of inflammation markers also associated with CVD. We observed the highest frequencies of activated CD8+ T cells in VCs, while EC and cART groups presented similar but slightly altered frequencies of this marker when compared to the HIVneg group. Regarding platelet activation, both HICs groups presented higher expression of P-selectin in platelets when compared to control groups. Monocyte subset analyses revealed lower frequencies of classical monocytes and increased frequencies of non-classical and intermediate monocytes among cART individuals and in EC when compared to HIV negative individuals, but none of the differences were significant. For VC, however, significant decreases in frequencies of classical monocytes and increases in the frequency of intermediate monocytes were observed in comparison to HIV negative individuals. The frequency of monocytes expressing tissue factor was similar among the groups on all subsets. In terms of plasma markers, VC had higher levels of many inflammatory markers, while EC had higher levels of VCAM-1 and ICAM-1 compared to control groups. Our data showed that VCs display increased levels of inflammation markers that have been associated with CVD risk. Meanwhile, ECs show signals of lower but persistent inflammation, comparable to the cART group, indicating the potential benefits of alternative therapies to decrease inflammation in this group.

Abstract Aims Elevated brain natriuretic peptide (BNP) and the N‐terminal fragment of its pro‐hormone (NT‐proBNP) have become established biomarkers for heart failure and are associated with cardiovascular morbidity and mortality. Investigating sources of inter‐individual heterogeneity, particularly genetic factors, could help better identify patients at risk of future cardiovascular disease. The aim of this study was to estimate the heritability of circulating NT‐proBNP levels, to perform a genome‐wide association study (GWAS) and gene‐candidate analysis focused on NPPB–NPPA genes on these levels, and to examine their association with cardiovascular or metabolic outcomes. Methods and results A total of 1555 individuals from the STANISLAS study were included. The heritability of circulating NT‐proBNP levels was estimated at 15%, with seven single nucleotide polymorphisms (SNPs) reaching the significant threshold in the GWAS. All above SNPs were located on the same gene cluster constituted of MTHFR, CLCN6, NPPA, NPPB, and C1orf167. NPPA gene expression was also associated with NT‐proBNP levels. Moreover, six other SNPs from NPPA–NPPB genes were associated with diastolic function (lateral e′ on echocardiography) and metabolic features (glycated haemoglobin). Conclusions The heritability of natriuretic peptides appears relatively low (15%) and mainly based on the same gene cluster constituted of MTHFR, CLCN6, NPPA, NPPB, and C1orf167. Natriuretic peptide polymorphisms are associated with natriuretic peptide levels and diastolic function. These results suggest that natriuretic peptide polymorphisms may have an impact in the early stages of cardiovascular and metabolic disease.

Abstract Background Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. Methods Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. Results Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = − 0.005; p

Monkeypox (MPX) transmission outside non-endemic countries has been reported since May 2022, rapidly evolving into a multi-country outbreak. A potential role of sexual contact in transmission dynamics, as well as a predominance of anogenital lesions, are remarkable features of current cases. Screening for sexually transmitted infections (STIs) plays an important role in the evaluation of patients with suspected MPX infection. Herein we report the first case of a patient diagnosed with both MPX and acute HIV infection in Latin America. He had no major complications during his clinical course, and antiretroviral therapy was promptly initiated. Diagnosis of acute HIV requires a high level of suspicion and appropriate laboratory investigation. Health practitioners need to consider this diagnosis while evaluating patients with suspected MPX with a recent unprotected sexual contact.

BackgroundThe HIV epidemic continues to disproportionately burden marginalized populations despite the availability of effective preventive and therapeutic interventions. Transgender women are severely affected by HIV worldwide including in Brazil and other low- and middle-income countries, with evidence of increasing new infections among young people. There is an urgent need for youth-specific HIV prevention and care interventions for young transgender women in Brazil. ObjectiveThis study aims to (1) address stigma in the Brazilian public health system and (2) reduce barriers to HIV care and prevention with systems navigation among young transgender women aged 18-24 years in Rio de Janeiro, Brazil. MethodsThe Brilhar e Transcender (BeT) study is a status-neutral, peer-led, single-arm digital intervention study enrolling 150 young transgender women in Rio de Janeiro, Brazil. The intervention was pilot tested and refined using data from a formative phase. The BeT intervention takes place over 3 months, is delivered remotely via mobile phone and in person by peers, and comprises three components: (1) BeT sessions, (2) digital interactions, and (3) automated messages. Eligibility criteria include identifying as transgender women, being aged 18-24 years, speaking in Portuguese, and living in the Rio de Janeiro metropolitan area in Brazil. The primary outcomes are HIV incidence, pre-exposure prophylaxis uptake, linkage to HIV care, and viral suppression. Primary outcomes were assessed at baseline and quarterly for 12 months. Participants respond to interviewer-based surveys and receive tests for HIV and sexually transmitted infections. ResultsThe study has been approved by the Brazilian and the US local institutional review boards in accordance with all applicable regulations. Study recruitment began in February 2022 and was completed in early July 2022. Plans are to complete the follow-up assessment of study participants on July 2023, analyze the study data, and disseminate intervention results by December 2023. ConclusionsInterventions to engage a new generation of transgender women in HIV prevention and care are needed to curb the epidemic. The BeT study will evaluate a digital peer-led intervention for young transgender women in Brazil, which builds on ways young people engage in systems and uses peer-led support to empower transgender youth in self-care and health promotion. A promising evaluation of the BeT intervention may lead to the availability of this rapidly scalable status-neutral HIV intervention that can be translated throughout Brazil and other low- and middle-income countries for young transgender women at high risk of or living with HIV. Trial RegistrationClinicalTrials.gov NCT05299645; https://clinicaltrials.gov/ct2/show/NCT05299645 International Registered Report Identifier (IRRID)DERR1-10.2196/44157

Summary: Background: By October 30, 2022, 76,871 cases of mpox were reported worldwide, with 20,614 cases in Latin America. This study reports characteristics of a case series of suspected and confirmed mpox cases at a referral infectious diseases center in Rio de Janeiro, Brazil. Methods: This was a single-center, prospective, observational cohort study that enrolled all patients with suspected mpox between June 12 and August 19, 2022. Mpox was confirmed by a PCR test. We compared characteristics of confirmed and non-confirmed cases, and among confirmed cases according to HIV status using distribution tests. Kernel estimation was used for exploratory spatial analysis. Findings: Of 342 individuals with suspected mpox, 208 (60.8%) were confirmed cases. Compared to non-confirmed cases, confirmed cases were more frequent among individuals aged 30–39 years, cisgender men (96.2% vs. 66.4%; p

Abstract Introduction: Routine patient care data are increasingly used for biomedical research, but such “secondary use” data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.

Abstract Background Weight gain commonly occurs among HIV-infected (HIV+) adults initiating modern ART regimens, and obesity is increasingly reported in this population. However, data regarding specific risk factors for obesity development after ART initiation are conflicting. Methods We retrospectively analyzed data from a cohort of HIV+ adults who initiated ART between January 1, 2000 and December 31, 2015 in Rio de Janeiro, Brazil. Body mass index (BMI) was assessed at ART initiation. Participants who were non-obese (BMI < 30kg/m2) at baseline and had ≥90 days of ART exposure were followed for development of obesity. Participants were censored at the time of obesity diagnosis or at end of follow-up (defined as death, loss to follow-up, end of study period or 2 years after their last weight measurement). Incidence rates were estimated using Poisson regression models and risk factor assessment was calculated using Cox regression models accounting for death and loss to follow-up as competing risks. Results Participants (n = 1,794) were 61.3% male, 48.3% white and had a median age of 36.3 years. At ART initiation, participants had a median BMI of 22.6kg/m2 and BMI category distribution was: underweight 14%, normal weight 56%, overweight 22% and obese 8%. Of the 1,567 non-obese participants followed after ART initiation, 76% gained weight, 44% increased their BMI category and 18% developed obesity. Median BMI at the end of follow-up was 24.7kg/m2 (0.4kg/m2 median annual change), the obesity incidence rate was 37.4 per 1000 person-years and the median time to obesity diagnosis was 1.9 years (vs. 4.7 years of follow-up for participants remaining non-obese). Factors associated with obesity after ART initiation included younger age at ART initiation, female sex, higher baseline BMI, lower baseline CD4+ T lymphocyte count, higher baseline HIV-1 RNA, having an integrase inhibitor as the most-used ART core drug and having diagnoses of hypertension and diabetes mellitus (Figure). Conclusion Obesity following ART initiation is frequent among HIV+ adults, with rates increasing in recent years. Both traditional (female sex) and HIV-specific (more advanced HIV disease, integrase inhibitor use) risk factors contribute importantly to obesity incidence following ART initiation. Disclosures All authors: No reported disclosures.

BackgroundInternet and mobile phones, widely available in Brazil, could be used to disseminate information about HIV prevention and to recruit gay, bisexual, and other cisgender men who have sex with men (MSM) to HIV prevention services. Data evaluating the characteristics of MSM recruited through different web-based strategies and estimating their cost and yield in the country are not available. ObjectiveWe aimed to describe a web-based recruitment cascade, compare the characteristics of MSM recruited to a large HIV prevention service in Rio de Janeiro according to web-based venues, and estimate the cost per participant for each strategy. MethodsWe promoted advertisements on geosocial networking (GSN) apps (Hornet and Grindr) and social media (Facebook and Instagram) from March 2018 to October 2019. The advertisements invited viewers to contact a peer educator to schedule a visit at the HIV prevention service. Performance of web-based recruitment cascade was based on how many MSM (1) were reached by the advertisement, (2) contacted the peer educator, and (3) attended the service. We used chi-square tests to compare MSM recruited through GSN apps and social media. The estimated advertisement cost to recruit a participant was calculated by dividing total advertisement costs by number of participants who attended the service or initiated preexposure prophylaxis (PrEP). ResultsAdvertisement reached 1,477,344 individuals; 1270 MSM contacted the peer educator (86 contacts per 100,000 views)—564 (44.4%), 401 (31.6%) and 305 (24.0%)—through social media, Grindr, and Hornet. Among the 1270 individuals who contacted the peer educator, 36.3% (n=461) attended the service with similar proportion for each web-based strategy (social media: 203/564, 36.0%; Grindr: 152/401, 37.9%; and Hornet: 107/305, 35.1%). MSM recruited through GSN apps were older (mean age 30 years vs 26 years; P

HIV-infected patients are at particular risk for invasive pneumococcal disease (IPD). We describe cases of IPD in people living with HIV/AIDS (PLWHA) and find associated risk factors for infection and death. Methods: A retrospective case-control study, nested in a cohort, including PLWHA with and without IPD, conducted in Brazil, 2005–2020. Controls were of the same gender/age and seen at the same time/place as cases. Results: We identified 55 episodes of IPD (cases) in 45 patients and 108 controls. The incidence of IPD was 964/100,000 person-years. A total of 42 of 55 (76.4%) IPD episodes presented with pneumonia and 11 (20%) with bacteremia without a focus and 38/45 (84.4%) were hospitalized. Blood cultures were positive in 54/55 (98.2%). Liver cirrhosis and COPD were the only factors associated with IPD in PLWHA in univariate analysis, although no associated factors were found in multivariate analysis. Penicillin resistance was found in 4/45 (8.9%). Regarding antiretroviral therapy (ART), 40/45 (88.9%) cases vs. 80/102 controls (74.1%) were in use (p = 0.07). Patients with HIV and IPD had a higher CD4 count of 267 cells/mm3 compared with the control group, in which it was 140 cells/mm3 (p = 0.027). Pneumococcal vaccination was documented in 19%. Alcoholism (p = 0.018), hepatic cirrhosis (p = 0.003), and lower nadir CD4 count (p = 0.033) were associated with the risk of death in patients with IPD. In-hospital mortality among PLWHA and IPD was 21.1%, and it was associated with thrombocytopenia and hypoalbuminemia, elevated band forms, creatinine, and aspartate aminotransferase (AST). Conclusions: The incidence of IPD in PLWHA remained high despite ART. The vaccination rate was low. Liver cirrhosis was associated with IPD and death.

Presbyopia describes the eye's physiological loss of the ability to see close objects clearly. The adaptation to different viewing distances, termed accommodation, is achieved by a change in the curvature of the eye lens induced by the ciliary muscle. A possible approach to correct presbyopia could be to detect the ciliary muscle's neuromuscular signals during accommodation and transfer these signals electronically to a biomimetic, micro-optical system to provide the necessary refractive power. As a preliminary step toward such a described system, a novel three-dimensional and biocompatible lift-off method was developed. In addition, the influence of the distance between the electrically conducting surfaces of the lens on the accommodated signal amplitudes was investigated. Compared to the conventional masking methods, this process has the advantage that three-dimensional surfaces can be masked with biocompatible gelling sugar by utilizing a direct writing process with a dispensing robot. Since gelling sugar can be used at room temperature and is water-soluble, the process presented is suitable for materials that should not be exposed to organic solvents or excessively high temperatures. Apart from investigating the shrinkage behavior of the gelling sugar during the physical vapor deposition (PVD) coating process, this paper also describes the approaches used to partially coat a commercial scleral contact lens with an electrically conductive material. It was shown that gelling sugar withstands the conditions during the PVD processes and a successful lift-off was performed. To investigate the influence of the spacing between the electrically conductive regions of the contact lens on the measured signals, three simplified electrode configurations with different distances were fabricated using a 3D printer. By testing these in an experimental setup, it could be demonstrated that the distance between the conductive surfaces has a significant influence on the amplitude. Regarding the described lift-off process using gelling sugar, it was found that the dispensing flow rate has a direct influence on the line uniformity. Future work should address the influence of the viscosity of the gelling sugar as well as the diameter of the cannula. It is assumed that they are the prevailing limitations for the lateral resolution.

Background Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome‐wide association study on SUA levels, and (3) investigate the association between certain single‐nucleotide polymorphisms and target organ damage. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non‐Invasif de la Santé des Lorrains Assurés Sociaux) study cohort is a single‐center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed ≈20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24‐hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome‐wide association study results highlighted multiple single‐nucleotide polymorphisms on the SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C‐reactive protein) levels, estimated glomerular filtration rate variation (visit 1–V4), carotid intima‐media thickness, and pulse wave velocity, rs16890979 was only associated with higher carotid intima‐media thickness. Conclusions Our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 gene, is associated with carotid intima‐media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease.

Abstract Biofeedback training has been used to access autonomically-controlled body functions through visual or acoustic signals to manage conditions like anxiety and hyperactivity. Here we examined the use of auditory biofeedback to improve accommodative responses to near visual stimuli in patients wearing single vision (SV) and multifocal soft contact lenses (MFCL). MFCLs are one evidence-based treatment shown to be effective in slowing myopia progression in children. However, previous research found that the positive addition relaxed accommodation at near, possibly reducing the therapeutic benefit. Accommodation accuracy was examined in 18 emmetropes and 19 myopes while wearing SVCLs and MFCLs (centre-distance). Short periods of auditory biofeedback training to improve the response (reduce the lag of accommodation) was performed and accommodation re-assessed while patients wore the SVCLs and MFCLs. Significantly larger accommodative lags were measured with MFCLs compared to SV. Biofeedback training effectively reduced the lag by ≥0.3D in individuals of both groups with SVCL and MFCL wear. The training was more effective in myopes wearing their habitual SVCLs. This study shows that accommodation can be changed with short biofeedback training independent of the refractive state. With this proof-of-concept, we hypothesize that biofeedback training in myopic children wearing MFCLs might improve the treatment effectiveness.

Background and AimsLittle is known about the effects of probiotics on inflammation in the context of chronic kidney disease (CKD). We investigated the association between probiotic intake and inflammation in patients with moderate-to-advanced CKD.MethodsWe performed a cross-sectional study of 888 patients with stage 3–5 CKD and data on serum C-reactive protein (CRP) levels and a concomitant food frequency questionnaire. We estimated the odds ratios (ORs) [95% confidence interval (CI)] for various CRP thresholds (>3, >4, >5, >6, and >7 mg/L) associated with three intake categories (no yoghurt, ordinary yoghurt, and probiotics from yoghurts or dietary supplements) and two frequency categories (daily or less than daily).ResultsThe 888 study participants (median age: 70; men: 65%) had a median estimated glomerular filtration rate of 28.6 mL/min/1.73 m2 and a median [interquartile range] CRP level of 3.0 [1.6, 7.0] mg/L. Fifty-seven percent consumed ordinary yoghurt and 30% consumed probiotic yoghurt. The median intake frequency for yoghurt and probiotics was 7 per week. Relative to participants not consuming yoghurt, the ORs [95% CI] for CRP > 6 or >7 mg/L were significantly lower for participants consuming ordinary yoghurt (0.58 [0.37, 0.93] and 0.57 [0.35, 0.91], respectively) and for participants consuming probiotics (0.54 [0.33, 0.9] and 0.48 [0.28, 0.81], respectively), independently of age, sex, body mass index, CKD stage, cardiovascular disease, and fibre, protein and total energy intakes. The ORs were not significantly lower for CRP thresholds >3, >4, and >5 mg/L and were not significantly greater in daily consumers than in occasional consumers.ConclusionWe observed independent associations between the consumption of yoghurt or probiotics and lower levels of inflammation in patients with CKD. There was no evidence of a dose-effect relationship.Clinical Trial Registration[https://www.clinicaltrials.gov/ct2/show/NCT03381950], identifier [NCT03381950].

Introdução: Doença pneumocócica invasiva (DPI) é definida como infecção confirmada por isolamento de Streptococcus pneumoniae em sítios estéreis. Em adultos, afeta idosos e grupos de risco, incluindo pessoas vivendo com HIV/AIDS (PVHA). Objetivos: Descrever os casos de DPI em PVHA atendidos em centro de referência no Rio de Janeiro, de 2005 a 2020; avaliar a incidência, aspectos clínico-laboratoriais e desfechos, e identificar variáveis associadas a DPI e a mortalidade. Métodos: Estudo retrospectivo do tipo caso- controle. Casos de DPI foram identificados pela Bacteriologia e dados dos pacientes buscados em prontuário eletrônico. Controles foram PVHA de mesmo gênero e faixa etária, atendidos no mesmo semestre e cenário que os casos. Análise estatística foi realizada utilizando R versão 4.1.0. Resultados: Foram identificados 55 episódios (casos) de DPI em 45 pacientes. Estes foram pareados com 110 controles, PVHA sem DPI. A incidência média de DPI foi de 1042 casos por 100.000 habitantes. Foram hospitalizados 84,4%, e 15,6% tratados ambulatorialmente. Cerca de 2/3 eram do sexo masculino, idade média foi de 42 anos. Focos de DPI foram pneumonia bacteriana (76,4%), bacteremia primária (20%) e meningite (3,6%). S.pneumoniae foi isolado em hemoculturas em 98,2% dos casos. Características associadas a DPI foram etilismo em 27,3% (p = 0,054), tabagismo em 45,5% (p = 0,09), uso de cocaína inalatória em 27,3% (p = 0,003). Dentre as comorbidades, apenas a cirrose hepática foi um fator associado a DPI, presente em 23,6% (p = 0,001). A frequência de uso de TARV nos casos foi de 89,1% e nos controles, de 74,5% (p = 0,048). A vacinação com Pn23 ocorreu em 21,8% dos casos e 19,1% nos controles. Resistência a penicilina ocorreu em 9,1% dos isolados. Dos 10 pacientes que evoluíram para óbito, 7 tinham cirrose hepática e o único hábito associado à morte foi etilismo. O nadir de CD4 foi mais baixo dentre os pacientes que evoluíram a óbito (89 cel/mm3 vs.184 cel/mm3 nos vivos, p = 0,058). Outras variáveis associadas a óbito foram: plaquetas, PCR e albumina sérica baixas, e bastonemia, ureia, creatinina, potassio, creatinofosfoquinase e TGO elevados; uso de aminas, ventilação mecânica, arritmia e insuficiência adrenal também foram associados a óbito. Conclusão: A incidência de DPI em PVHA permaneceu alta apesar do uso frequente de TARV. A taxa de vacinação foi baixa. Etilismo e uso de cocaína foram associados a DPI. Baixas contagens de CD4 foram associadas a óbito.

Background and Aims: Beverages are an important aspect of diet, and their quality can possibly affect health. The Healthy Beverage Index (HBI) has been developed to take into account these effects. This study aimed to highlight the relationships between health and beverage quality by assessing the association of the HBI and its components with kidney and cardiometabolic (CM) outcomes in an initially healthy population-based familial cohort.Methods: This study included 1,271 participants from the STANISLAS cohort. The HBI, which includes 10 components of habitual beverage consumption, was calculated. Associations of the HBI and its components with estimated glomerular filtration rate (eGFR), albuminuria, hypertriglyceridemic waist (HTG waist), metabolic syndrome (MetS), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LV mass) were analyzed using multivariable linear or logistic regression models.Results: The median HBI score was 89.7 (78.6–95) out of 100 points. While the overall HBI score was not significantly associated with any of the studied outcomes, individual HBI components were found differently associated with the outcomes. cfPWV and cIMT were lower in participants who did not meet the full-fat milk criteria (p = 0.03 and 0.001, respectively). In men, higher cfPWV was observed for the “low Fat milk” (p = 0.06) and “alcohol” (p = 0.03) non-adherence criteria. Odds of HTG waist were higher with the non-adherence to sugar-sweetened beverages criteria (p < 0.001). eGFR was marginally higher with non-adherence to the coffee/tea criteria (p = 0.047).Conclusions: In this initially healthy population, HBI components were differently associated with kidney and cardiometabolic outcomes, despite a good overall HBI score. Our results highlight specific impacts of different beverage types and suggest that beverages could have an impact on kidney and cardiometabolic health.

BackgroundIn many parts of the world, including Brazil, uptake for biomedical interventions has been insufficient to reverse the HIV epidemic among key populations at high risk for HIV, including men who have sex with men. Young MSM (YMSM), particularly Black YMSM, have high HIV incidence, low viral suppression, and low preexposure prophylaxis (PrEP) uptake and adherence. Therefore, novel approaches to increase the HIV biomedical interventions uptake by YMSM are urgently needed. ObjectiveWe describe the Conectad@s Project, which aims to: (1) estimate the prevalence and incidence of HIV and other sexually transmitted infections, the onset of sexual risk behavior, and barriers to biomedical interventions among YMSM aged 18 to 24 years in Rio de Janeiro, Brazil; and (2) conduct a technology-based adherence intervention study to promote a rapid linkage of YMSM to HIV care or prevention, and support and sustain adherence. MethodsA cross-sectional survey will be conducted with 400 YMSM recruited using respondent-driven sampling (RDS) adapted for social media-based sampling, preceded by a formative phase. HIV and sexually transmitted infections testing will be conducted, including early HIV infection biomarker detection. Behavioral, partnership, network, and structural measures will be collected through structured questionnaires. All individuals recruited for the survey will have access to HIV risk assessment, antiretroviral therapy (ART), PrEP, prevention counseling, and a technology-based adherence intervention. Those who accept the adherence intervention will receive weekly text messages via a social networking app (WhatsApp) for 24 weeks, with follow-up data collected over 48 weeks. ResultsThe Conectad@s project has been approved by our local institutional review board (#CAAE 26086719.0.0000.4262) in accordance with all applicable regulations. Questionnaires for the RDS survey and intervention were developed and tested in 2020, formative interviews were conducted in January and February 2021 to guide the development of the RDS, and enrollment is planned to begin in early 2022. ConclusionsThe Conectad@s Project is a vanguard study that, for the first time, will apply digital RDS to sample and recruit YMSM in Brazil and rapidly connect them to ART, PrEP, or prevention counseling through a technology-based adherence intervention. RDS will allow us to estimate HIV prevalence among YMSM and measure HIV infection biomarkers in the context of the onset of risky behavior. The data will lay the groundwork to adapt and implement HIV prevention strategies, identify barriers to the earliest HIV infection diagnosis, immediate ART or PrEP initiation, and detect new clusters of HIV transmission. International Registered Report Identifier (IRRID)DERR1-10.2196/34885

Anterior segment optical coherence tomography (AS-OCT), being non-invasive and well-tolerated, is the method of choice for an in vivo investigation of ciliary muscle morphology and function. The analysis requires the segmentation of the ciliary muscle, which is, when performed manually, both time-consuming and prone to examiner bias. Here, we present a convolutional neural network trained for the automatic segmentation of the ciliary muscle in AS-OCT images. Ciloctunet is based on the Freiburg U-net and was trained and validated using 1244 manually segmented OCT images from two previous studies. An accuracy of 97.5% for the validation dataset was achieved. Ciloctunet’s performance was evaluated by replicating the findings of a third study with 180 images as the test data. The replication demonstrated that Ciloctunet performed on par with two experienced examiners. The intersection-over-union index (0.84) of the ciliary muscle thickness profiles between Ciloctunet and an experienced examiner was the same as between the two examiners. The mean absolute error between the ciliary muscle thickness profiles of Ciloctunet and the two examiners (35.16 µm and 45.86 µm) was comparable to the one between the examiners (34.99 µm). A statistically significant effect of the segmentation type on the derived biometric parameters was found for the ciliary muscle area but not for the selective thickness reading (“perpendicular axis”). Both the inter-rater and the intra-rater reliability of Ciloctunet were good to excellent. Ciloctunet avoids time-consuming manual segmentation, thus enabling the analysis of large numbers of images of ample study cohorts while avoiding possible examiner biases. Ciloctunet is available as open-source.

Background: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is a multicenter, randomized, placebo-controlled trial, designed to test whether a statin medication can prevent cardiovascular disease in people with HIV. REPRIEVE recently completed enrollment of 7557 participants at over 100 clinical sites globally. Participant groups of focus were women, and racial and ethnic minorities. Objective: To describe recruitment methods and strategies developed by the REPRIEVE Clinical Coordinating Center (CCC) and share best practices learned from the recruitment process. Methods: Enrollment targets were agreed upon with the primary funder, the National Heart, Lung, and Blood Institute (NHLBI) and were milestone driven. Milestones included number of sites activated, number of participants enrolled within specific time frames, and proportion of women and minorities enrolled. Strategies to achieve these milestones included structured interviews with site-designated REPRIEVE Recruitment Champions to develop best practices, development of a multimedia campaign, and site level recruitment support. Results: Recruitment initiated March, 2015 and completed March, 2019. The final accrual target was 7500 participants over 48 months. The trial met this target within the time specified. Overall, 10,613 screens were completed, 48% of participants enrolled from sites outside of North America, 32% were female, 44% were Black or African American, and 25% were Hispanic or Latino. Conclusions: REPRIEVE met its overall projected recruitment goal by using multiple, simultaneous strategies to specifically target a diverse population including minority subgroups. REPRIEVE benefited from the development of recruitment strategies with clear targets and communication of accrual targets to study teams.

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity. [ABSTRACT FROM AUTHOR]

Commercial land use management that focuses on a future-oriented urban and regional development must address multiple goals. Effective policy mixes need to simultaneously (1) improve city-regional and inter-municipal cooperation, (2) reduce land take, and (3) assure the long-term economic development of a region. Using the Northern Black Forest in Germany as a case study, we brought together planning and land use research with public policy analysis. We applied cross-impact balances (CIB) to build and analyze a participatory policy-interaction model. Together with a group of 12 experts, we selected effective individual measures to reach each of the three goals and analyzed their interactions. We then assessed the current policy mix and designed alternative policy mixes. The results demonstrate that current approaches to commercial land use management present internal contradictions and generate only little synergies. Implementing innovative measures on a stand-alone basis runs the risk of not being sufficiently effective. In particular, the current practice of competing for municipal marketing and planning of commercial sites has inhibiting effects. We identified alternative policy mixes that achieve all three goals, avoid trade-offs, and generate significant synergy effects. Our results point towards a more coherent and sustainable city-regional (commercial) land-use governance.

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p