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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.

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: 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 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.

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.

Summary: Background: Men who have sex with men (MSM) and transgender women (TGW) are disproportionally affected by HIV infection in Latin America. This study aims to assess pre-exposure prophylaxis (PrEP) preferences among sexual and gender minorities (SGM) and identify attributes and levels that are related to PrEP uptake and adherence, both crucial for PrEP success. Methods: We conducted a discrete choice experiment (DCE) among SGM from all Brazilian regions (September–December/2020). The survey was administered face-to-face (five Brazilian capitals) and online (entire country). We used a D-efficient zero-prior blocked experimental design to select 60 paired-profile DCE choice tasks. Findings: The total sample size was 3924 (90.5% MSM; 7.2% TGW and 2.3% non-binary or gender diverse persons). In random-effects logit models, highest levels of protection and “no side effects” were the most important attribute levels. For “presentation”, injectable and implant were preferred over oral. Participants were willing to accept a 4.1% protection reduction to receive injectable PrEP or a 4.2% reduction if PrEP were taken monthly. The largest class in the latent class models was defined predominantly by the preference for the highest HIV protection level (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

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

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

Introduction Pre-exposure prophylaxis (PrEP) is an important and well-established prevention strategy for sexual acquisition of HIV. In Brazil, transgender women (TGW) and men who have sex with men (MSM) bear the largest burden among key populations. Little is known about preferences for PrEP characteristics in these vulnerable populations in Latin America. The goal of this study is to investigate preferences of TGW and MSM with respect to PrEP characteristics, whether current user or not, and to assess any attributes and levels that may improve the decision to start using PrEP (uptake) and optimal continuity of use (adherence), which are important dimensions for PrEP success.Methods and analysis We hereby outline the protocol of a discrete choice experiment (DCE) to be conducted among TGW and MSM in Brazil. The study will be carried out in two phases. The first phase involves literature review and qualitative approaches including in-depth interviews to inform the development of the DCE (attributes and levels). The second phase entails the DCE survey and supporting questions pertaining to sociodemographic and risk behaviour information. The survey is aimed at current PrEP users and non-users, consisting of two modes of administration: face to face in five Brazilian capitals (Rio de Janeiro, Brasília, Manaus, Porto Alegre and Salvador) and online targeting the entire country. A D-efficient zero-prior blocked experimental design will be used to select 60 paired-profile DCE choice tasks, in which participants will be randomly assigned to one of four groups and presented with a set of 15 choice tasks. The planned sample size is 1000 volunteers.Ethics, timeline and dissemination The study was approved by Comitê de Ética em Pesquisa—Instituto Nacional de Infectologia Evandro Chagas—INI/FIOCRUZ, CEP/INI, CAAE 28416220.2.1001.5262, approval number 3.979.759 in accordance with the Comissão Nacional de Ética em Pesquisa (CONEP—Brazilian National Board of Research Ethics). The study will be conducted between 2020 and 2021. The results will be disseminated to the scientific community and to the public in general through publications in published in peer-reviewed journals and in scientific conferences.

Abstract Objectives To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection. Methods We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8+CD38+HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann–Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses. Results IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8+ T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group. Conclusions Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8+ T cell activation.

Abstract Background Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n = 5) and (2) elite controllers (ECs; n = 6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes. Results Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were

Introduction: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. Methods: 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. Results: Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8–11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9–1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3–2.2) and 3.2-fold (95% CI 1.5–7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7–94.6] for 12 months and 80.9% [95% CI 77.2–84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9–100.0] for 12 months and 99.0 [95% CI 97.6–99.7] for 36 months). Conclusions: Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology. Keywords: HPV, HIV, Women, Cohort, Incidence

Abstract Background Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). Methods The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. Results Treatment costs of GT1-HCV patients were PPP$ 43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$ 19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. Conclusion Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries.

The aim of early combined antiretroviral therapy (cART) of HIV is to limit the seeding of the viral reservoir during the initial phase of infection and, consequently, decrease intrahost viral diversity. Here, we assessed the effect of early cART on size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected Brazilian individuals diagnosed at the acute phase of infection, before (PREART) and 12 months (M12ART) after suppressive cART. HIV proviral reservoir size was determined by quantitative real-time PCR; intrahost viral diversity of the env C2-V3 region was assessed by single genome amplification or next-generation sequencing in PBMC and plasma, respectively. Mean nucleotide diversity (π) and normalized Shannon entropy (HSN) were used to infer the complexity of the viral population. Compared to PREART, M12ART saw an immunological recovery with a gain of ∼200 CD4+ T cells (P = 0.008) and a normalization of the CD4/CD8 ratio [1.0 (IQR: 0.88–1.18), P = 0.016], as well as a significant decrease in HIV-1 RNA (∼4 log, P = 0.004) and DNA (∼1 log, P = 0.002) levels. The median time to achieve viral suppression was 3 months (IQR: 2.8–5.8 months). The high intermixing between sequences from both visits suggests that the HIV-1 DNA reservoir remained remarkably stable under cART. After 1 year of cART, there was a minor reduction in proviral π (PreART = 0.20 vs. M12ART = 0.10; P = 0.156) but a significant decrease in HSN (PreART = 0.41 vs. M12ART = 0.25; P = 0.019). We found no correlation between π or HSN at PreART and the rate of HIV DNA decay, T CD4+ counts, or CD4/CD8 ratio at M12ART. Based on a small cohort of Brazilian infected individuals under early cART and analyses of the env region, 1 year of follow-up suggested a reservoir size reduction, allowed a significant decrease of HIV-1 complexity, and achieved immunological restoration regardless of the initial HIV-1 plasma viral load, CD4+ T cell counts, or HIV-1 subtype. However, further studies in the Brazilian setting aiming a longer follow-up and larger cohort are required in this field.

Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) infection remains an important cause of new HIV infections worldwide, especially in low and middle-resource limited countries. Safety data from studies involving pregnant women and prenatal antiretroviral (ARV) exposure are still needed once these studies are often small and with a limited duration to assess adverse drug reactions (ADR). The aim of this study was to estimate the incidence of ADR related to the use of antiretroviral therapy (ART) in pregnant women in two referral centers in Rio de Janeiro State. A prospective study was carried out from February 2005 to May 2006. Women were classified according to their ART status during pregnancy diagnosis: ARV-experienced (ARTexp) or ARV-naïve (ARTn). Two hundred fourteen HIV-infected pregnant women were included: 36 ARTexp and 178 ARTn. ARTexp women have not experienced ADR. Among ARTn, 20.2% presented ADR. Incidence rate of ADR was 70.8 per 1000 person-months and the most common ADRs observed were: gastrointestinal (belly or abdominal cramps, diarrhea, nausea and vomit) in 16.3%, cutaneous (pruritus and rash) in 6.2%, anemia (2.2%) and hepatitis (1.7%). The frequency of obstetrical complications, pre-term delivery, low birth weight and birth abnormalities was low in this population. ADRs ranged from mild to moderate intensity, none of them being potentially fatal. Only in a few cases it was necessary to discontinue ART. In conclusion, the high effectiveness of ARV for HIV prevention of MTCT (PMTCT) overcomes the risk of ADR. Keywords: HIV, Antiretroviral, Prevention of mother-to-child transmission, Adverse drug reaction, Toxicity

Objectives: To describe the access to the interventions for the prevention of Human Immunodeficiency Virus (HIV) mother to child transmission and mother to child transmission rates in the outskirts of Rio de Janeiro, from 1999 to 2009. Methods: This is a retrospective cohort study. Prevention of HIV mother to child transmission interventions were accessed and mother to child transmission rates were calculated. Results: The study population is young (median: 26 years; interquartile range: 22.0–31.0), with low monthly family income (40.4% up to one Brazilian minimum wage) and schooling (62.1% less than 8 years). Only 47.1% (n = 469) knew the HIV status of their partner; of these women, 39.9% had an HIV-seronegative partner. Among the 1259 newborns evaluated, access to the antenatal, intrapartum and postpartum prevention of HIV mother to child transmission components occurred in 59.2%, 74.2%, and 97.5% respectively; 91.0% of the newborns were not breastfed. Overall 52.7% of the newborns have benefited from all the recommended interventions. In subsequent pregnancies (n = 289), 67.8% of the newborns received the full package of interventions. The overall rate of HIV vertical transmission was 4.7% and the highest annual rate occurred in 2005 (7.4%), with no definite trend in the period. Conclusions: Access to the full package of interventions for the prevention of HIV vertical transmission was low, with no significant trend of improvement over the years. The vertical transmission rates observed were higher than those found in reference services in the municipality of Rio de Janeiro and in the richest regions of the country. Keywords: HIV, HIV vertical transmission, Antiretroviral chemoprophylaxis, Cohort studies, Brazil

The introduction of highly active antiretroviral therapy during the 1990s was crucial to the decline in the rates of morbidity and death related to the acquired immunodeficiency syndrome (AIDS) and turned human immunodeficiency virus (HIV) infection into a chronic condition. Consequently, the HIV/AIDS population is becoming older. The aim of this study was to describe the immunological, clinical and comorbidity profile of an urban cohort of patients with HIV/AIDS followed up at Instituto de Pesquisa Clinica Evandro Chagas, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Retrospective data from 2307 patients during January 1st, 2008 and December 31st, 2008 were collected. For continuous variables, Cuzick's non-parametric test was used. For categorical variables, the Cochran-Armitage non-parametric test for tendency was used. For all tests, the threshold for statistical significance was set at 5%. In 2008, 1023 (44.3%), 823 (35.7%), 352 (15.3%) and 109 (4.7%) were aged 18-39, 40-49, 50-59 and >60 years-old, respectively. Older and elderly patients (>40 years) were more likely to have viral suppression than younger patients (18-39 years) (p 0.001). No significant difference in the latest CD4+ T lymphocyte count in the different age strata was observed, although elderly patients (> 50 years) had lower CD4+ T lymphocyte nadir (p 0.02). The number of comorbidities increased with age and the same pattern was observed for the majority of the comorbidities, including diabetes mellitus, dyslipidemia, hypertension, cardiovascular diseases, erectile dysfunction, HCV, renal dysfunction and also for non-AIDSrelated cancers (p 0.001). With the survival increase associated to successful antiretroviral therapy and with the increasing new infections among elderly group, the burden associated to the diagnosis and treatment of the non-AIDS related HIV comorbidities will grow. Longitudinal studies on the impact of aging on the HIV/AIDS population are still necessary, especially in resource-limited countries.

Since record linkage errors can bias measures of disease occurrence and association, it is important to assess their accuracy. The aim of this study is to assess the accuracy of a multiple pass probabilistic record linkage strategy to identify deaths among persons reported to the Brazilian AIDS surveillance database. An HIV/AIDS national surveillance database (N = 559,442) was linked to a total of 6,444,822 deaths registered (all causes) in the Brazilian mortality database. To estimate standard measures of accuracy, we selected all AIDS cases with a date of death registered in the surveillance database from 2002 to 2005 (N = 19,750) and 38,675 cases known to be alive in 2006. The linkage strategy presented a sensitivity of 87.6% (95%CI: 87.1-88.2), a specificity of 99.6% (95%CI: 99.6-99.7), and a positive predictive value of 99.2% (95%CI: 99.1-99.3). We observed a small variation in the validity measures according to some putative predictors of mortality. Our findings suggest that even large and heterogeneous databases can be linked with a satisfactory accuracy.É importante avaliar a acurácia de relacionamento de dados, já que erros podem enviesar as medidas de ocorrência e de associação de doenças. O objetivo desse estudo é verificar a acurácia da estratégia de relacionamento probabilístico de banco de dados em identificar óbitos entre casos de AIDS notificados no Sistema de Informações de Agravos de Notificação (SINAN). O banco de dados de pessoas com HIV/AIDS (N = 559.442) foi relacionado a 6.444.822 óbitos (todas as causas) registrados no Sistema de Informações sobre Mortalidade (SIM). Para estimar as medidas de acurácia, foram selecionados todos os casos de AIDS com datas de óbito registradas no SINAN-AIDS de 2002 a 2005 (N = 19.750) e 38.675 casos sabidamente vivos em 2006. A sensibilidade foi de 87,6% (IC95%: 87,1-88,2), a especificidade de 99,6% (IC95%: 99,6-99,7) e o valor preditivo de 99,2% (IC95%: 99,1-99,3). Sensibilidade foi 12% menor para os casos com menos de 13 anos. Foram observadas pequenas variações nas medidas de validação segundo algumas variáveis preditoras de mortalidade. Conclui-se que bancos de dados grandes e heterogêneos podem ser relacionados com acurácia satisfatória.

The lens epithelium-derived growth factor p75 (LEDGF/p75), coded by the PSIP1 gene, is an important host co-factor that interacts with HIV-1 integrase to target integration of viral cDNA into active genes. The aim of this study was to investigate the association of SNPs in the PSIP1 gene with disease outcome in HIV-1 infected patients. We performed a genetic association study in a cohort of 171 HIV-1 seropositive Brazilian individuals classified as rapid progressors (RP, n = 69), typical progressors (TP, n = 79) and long-term nonprogressors (LTNP, n = 23). The exonic SNP rs61744944 and 9 tag SNPs were genotyped. A group of 192 healthy subjects was analyzed to determine the frequency of SNPs and haplotypes in the general population. Linkage disequilibrium (LD) analyses indicated that the SNPs analyzed were not in high LD (r2

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.

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

BackgroundLong-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) has proven efficacious in randomized controlled trials. Further research is critical to evaluate its effectiveness in real-world settings and identify effective implementation approaches, especially among young sexual and gender minorities (SGMs). ObjectiveImPrEP CAB Brasil is an implementation study aiming to generate critical evidence on the feasibility, acceptability, and effectiveness of incorporating CAB-LA into the existing public health oral PrEP services in 6 Brazilian cities. It will also evaluate a mobile health (mHealth) education and decision support tool, digital injection appointment reminders, and the facilitators of and barriers to integrating CAB-LA into the existing services. MethodsThis type-2 hybrid implementation-effectiveness study includes formative work, qualitative assessments, and clinical steps 1 to 4. For formative work, we will use participatory design methods to develop an initial CAB-LA implementation package and process mapping at each site to facilitate optimal client flow. SGMs aged 18 to 30 years arriving at a study clinic interested in PrEP (naive) will be invited for step 1. Individuals who tested HIV negative will receive mHealth intervention and standard of care (SOC) counseling or SOC for PrEP choice (oral or CAB-LA). Participants interested in CAB-LA will be invited for step 2, and those with undetectable HIV viral load will receive same-day CAB-LA injection and will be randomized to receive digital appointment reminders or SOC. Clinical appointments and CAB-LA injection are scheduled after 1 month and every 2 months thereafter (25-month follow-up). Participants will be invited to a 1-year follow-up to step 3 if they decide to change to oral PrEP or discontinue CAB-LA and to step 4 if diagnosed with HIV during the study. Outcomes of interest include PrEP acceptability, choice, effectiveness, implementation, and feasibility. HIV incidence in the CAB-LA cohort (n=1200) will be compared with that in a similar oral PrEP cohort from the public health system. The effectiveness of the mHealth and digital interventions will be assessed using interrupted time series analysis and logistic mixed models, respectively. ResultsDuring the third and fourth quarters of 2022, we obtained regulatory approvals; programmed data entry and management systems; trained sites; and performed community consultancy and formative work. Study enrollment is programmed for the second quarter of 2023. ConclusionsImPrEP CAB Brasil is the first study to evaluate CAB-LA PrEP implementation in Latin America, one of the regions where PrEP scale-up is most needed. This study will be fundamental to designing programmatic strategies for implementing and scaling up feasible, equitable, cost-effective, sustainable, and comprehensive alternatives for PrEP programs. It will also contribute to maximizing the impact of a public health approach to reducing HIV incidence among SGMs in Brazil and other countries in the Global South. Trial RegistrationClinicaltrials.gov NCT05515770; https://clinicaltrials.gov/ct2/show/NCT05515770 International Registered Report Identifier (IRRID)PRR1-10.2196/44961

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.

The emergence of the COVID-19 pandemic reinforced the central role of the One Health (OH) approach, as a multisectoral and multidisciplinary perspective, to tackle health threats at the human-animal-environment interface. This study assessed Brazilian preparedness and response to COVID-19 and zoonoses with a focus on the OH approach and equity dimensions. We conducted an environmental scan using a protocol developed as part of a multi-country study. The article selection process resulted in 45 documents: 79 files and 112 references on OH; 41 files and 81 references on equity. The OH and equity aspects are poorly represented in the official documents regarding the COVID-19 response, either at the federal and state levels. Brazil has a governance infrastructure that allows for the response to infectious diseases, including zoonoses, as well as the fight against antimicrobial resistance through the OH approach. However, the response to the pandemic did not fully utilize the resources of the Brazilian state, due to the lack of central coordination and articulation among the sectors involved. Brazil is considered an area of high risk for emergence of zoonoses mainly due to climate change, large-scale deforestation and urbanization, high wildlife biodiversity, wide dry frontier, and poor control of wild animals' traffic. Therefore, encouraging existing mechanisms for collaboration across sectors and disciplines, with the inclusion of vulnerable populations, is required for making a multisectoral OH approach successful in the country.

Paracoccidioidomycosis (PCM) is one of the main endemic systemic mycoses in Latin America, usually occurring in rural areas. When PCM occurs simultaneously with underlying immunosuppressive conditions, it can present as an opportunistic disease. Between 2000 and 2017, literature reported around 200 PCM cases in people living with HIV/AIDS (PLWHA). To address research gaps on this co-infection and to study its possible temporal changes in the last decade, we performed an active co-infection case search on the HIV/AIDS and PCM cohorts from a Brazilian reference center database from 1989 to 2019. We found 20 PLWHA among 684 PCM patients (2.92%), predominantly male (70.0%) and urban workers (80.0%). The median age of patients was higher in the 2010-2019 decade (p = 0.006). The occurrence of PCM in PLWHA was lower when compared with other fungal diseases. Although 50.0% of the patients had already been diagnosed with HIV infection and presented CD4+ T cell counts greater than 200/mm3 at the time of PCM diagnosis, the suspicion of immunosuppression in the context of atypical and more severe clinical forms of PCM revealed the diagnosis of HIV infection in 35.0% of the patients. Two (10.0%) patients had an evolution compatible with immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy (ART).We highlight the importance of considering a PCM diagnosis in PLWHA to prevent a late-onset treatment and progression to severe manifestations and unfavorable outcomes. In addition, HIV investigation is recommended in PCM patients, especially those with atypical and more severe clinical presentations.

The COVID-19 virus infection caused by the new SARS-CoV-2 was first identified in Rio de Janeiro (RJ), Brazil, in March 2020. Until the end of 2021, 504,399 COVID-19 cases were confirmed in RJ, and the total death toll reached 68,347. The Evandro Chagas National Institute of Infectious Diseases from Oswaldo Cruz Foundation (INI-Fiocruz) is a referral center for treatment and research of several infectious diseases, including COVID-19 and Chagas disease (CD). The present study aimed to evaluate the impact of COVID-19 on in-hospital mortality of patients with CD during the COVID-19 pandemic period. This observational, retrospective, longitudinal study evaluated all patients with CD hospitalized at INI-Fiocruz from May 1, 2020, to November 30, 2021. One hundred ten hospitalizations from 81 patients with CD (58% women; 68 ± 11 years) were evaluated. Death was the study's main outcome, which occurred in 20 cases. The mixed-effects logistic regression was performed with the following variables to test whether patients admitted to the hospital with a COVID-19 diagnosis would be more likely to die than those admitted with other diagnoses: admission diagnosis, sex, age, COVID-19 vaccination status, CD clinical classification, and the number of comorbidities. Results from multiple logistic regression analysis showed a higher risk of in-hospital mortality in patients diagnosed with COVID-19 (OR 6.37; 95% CI 1.78–22.86) compared to other causes of admissions. In conclusion, COVID-19 infection had a significant impact on the mortality risk of INI-Fiocruz CD patients, accounting for one-third of deaths overall. COVID-19 presented the highest percentage of death significantly higher than those admitted due to other causes during the COVID-19 pandemic.

Abstract: We assessed the proportions and causes of the underreporting of deaths among people living with HIV (PLHIV) in Rio de Janeiro, Brazil, from 2014 to 2019. Demographic variables, mention of tuberculosis (TB), and CD4 cell counts closest to death were used to compare those who had HIV/AIDS mentioned on their death certificate (HMDC) to those who did not. Out of 10,698 deaths, 2,863 (26.8%) had no HMDC, from which 412 (14.4%) had external underlying cause. After excluding deaths from external causes, we found that 24% still had no HMDC. Age ≥ 40 years (OR = 1.75; 95%CI: 1.52-2.01), non-white race/ethnicity (OR = 1.16; 95%CI: 1.02-1.31), the male gender (OR = 1.25; 95%CI: 1.11-1.42), higher CD4 cell counts closest to death (OR = 1.14; 95%CI: 1.12-1.16), absence of TB (OR = 4.86; 95%CI: 3.76-6.29) and not dying within a hospital (OR = 2.61; 95%CI: 2.31-2.95) were associated with increased probabilities of not having HMDC. The proportion of deaths with no HMDC increased from 18.7% to 35.1% between 2014 and 2019. The high proportion of underreported deaths in Rio de Janeiro indicates that HIV/AIDS mortality coefficients in the state may be underestimated. With the changing patterns of mortality of PLHIV, physicians are advised to consider the broader clinical spectrum of HIV infection, and surveillance officers should improve death monitoring.

Abstract Background HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. Case presentation Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4+ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009–2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B1). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B2) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8+ and CD4+ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. Conclusions Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.

Background Trans women face disproportionate burden of adverse health outcomes, including mental health issues. Very little is known about suicidal behavior among trans women in low- and middle-income settings, such as Brazil. We aimed to estimate the prevalence of lifetime suicidal behavior and to identify its associated factors among Brazilian trans women. Methods This was a cross-sectional study conducted among 345 trans women living in Rio de Janeiro, Brazil. We examined the prevalence of suicidal behavior (ideation and suicide attempt) and its associated factors using stepwise backward Poisson regression analysis with robust variance. Results Suicidal ideation was present among 47.25% of participants, and the prevalence of lifetime suicide attempt was 27.25%. Trans women with prior physical violence perpetrated by a family member had significantly higher prevalence of suicidal ideation (adjusted prevalence ratios [aPR]1.37), whereas those who reported sex work had lower prevalence ratio of suicidal ideation (aPR 0.76). Suicide attempt was significantly associated with living alone (aPR 1.48), physical violence by a casual partner (aPR 1.92), and sexual violence by a family member (aPR 1.69). Depression was significantly associated with both outcomes (aPR 1.90 for suicidal ideation and aPR 2.21 for suicide attempt). Conclusion Suicidal behavior prevalence rates among Brazilian trans women were alarming and directly linked to violence and poor mental health. Effective mental health and public health policies addressing violence against trans women are urgently needed to prevent suicidal behavior among this highly vulnerable population.

ABSTRACT OBJECTIVE To estimate the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the state of Rio de Janeiro, Brazil. METHODS Data were collected on 2,857 blood donors from April 14 to 27, 2020. This study reports crude prevalence of antibodies to SARS-CoV-2, population weighted prevalence for the state, and prevalence adjusted for test sensitivity and specificity. Logistic regression models were used to establish the correlates of SARS-CoV-2 prevalence. For the analysis, we considered collection period and site, sociodemographic characteristics, and place of residence. RESULTS The proportion of positive tests for SARS-Cov-2, without any adjustment, was 4.0% (95%CI 3.3–4.7%), and the weighted prevalence was 3.8% (95%CI 3.1–4.5%). We found lower estimates after adjusting for test sensitivity and specificity: 3.6% (95%CI 2.7–4.4%) for the non-weighted prevalence, and 3.3% (95%CI 2.6–4.1%) for the weighted prevalence. Collection period was the variable most significantly associated with crude prevalence: the later the period, the higher the prevalence. Regarding sociodemographic characteristics, the younger the blood donor, the higher the prevalence, and the lower the education level, the higher the odds of testing positive for SARS-Cov-2 antibody. We found similar results for weighted prevalence. CONCLUSIONS Our findings comply with some basic premises: the increasing trend over time, as the epidemic curve in the state is still on the rise; and the higher prevalence among both the youngest, for moving around more than older age groups, and the less educated, for encountering more difficulties in following social distancing recommendations. Despite the study limitations, we may infer that Rio de Janeiro is far from reaching the required levels of herd immunity against SARS-CoV-2.

RESUMO: Introdução: A aparente estabilidade da mortalidade por aids no país na última década encobre uma gama de cenários, com dois terços dos estados apresentando taxa padronizada de mortalidade por aids (TPMA) significativamente acima da média nacional e/ou em tendência ascendente. No Rio de Janeiro, a TPMA vem mantendo-se alta e estável ao longo dos anos; atualmente o estado ocupa a segunda posição no ranking nacional desse indicador. Objetivo: Examinar tendências temporais em causas de óbito na busca de padrões diferenciais que contribuam para o entendimento da mortalidade por aids no estado. Metodologia: Foram analisadas causas de óbito em qualquer campo das declarações de óbito constantes do Sistema de Informação sobre Mortalidade (SIM) entre 1999 e 2015 para indivíduos ≥ 15 anos. Doenças cardiovasculares, malignidades não relacionadas à aids, causas externas, diabetes melito e tuberculose foram estabelecidas pela menção ou não de seus códigos conforme a Classificação Estatística Internacional de Doenças e Problemas Relacionados com a Saúde (CID-10) nas declarações de óbito. Modelos lineares generalizados com efeitos mistos foram usados para descrever odds ratios relativas a 1999 e variações anuais médias ajustadas. Resultados: Verificaram-se o aumento proporcional em causas externas e doenças geniturinárias e, sobretudo, o persistente papel desempenhado pela tuberculose, impactando diferencialmente a mortalidade por aids no estado, em um cenário de alta mortalidade por doenças infecciosas. Conclusão: Os achados reforçam a manutenção da tuberculose na mortalidade de pessoas vivendo com HIV/aids (PVHA) no Rio de Janeiro e chamam a atenção para a necessidade de avaliar determinantes individuais atuando na redução da sobrevida desses pacientes, de forma a aprimorar o programa de controle do HIV/aids no estado.

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Abstract Background Tuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy. Methods This was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV” (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables. Results A total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%). Conclusion Our results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

Background: The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still represent a major cause of death and hospitalization in this population. In this study, we review the trends in opportunistic illnesses incidence rates and compare the results observed in high-income settings with that for low/middle-income settings, with special attention given to studies from Brazil. Methods: We systematically searched Pubmed, Web of Science, Lilacs and Google scholar for publications on HIV associated opportunistic illness. Studies reporting rates based on person-time for all opportunistic illnesses and/or the three opportunistic infections of interest, namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium avium complex were included. Results: Significant reductions in the incidence rates were demonstrated for opportunistic illnesses overall and also for the specific opportunistic infections included in the present study, both in high and low/middle-income settings. Out of the 37 studies included in the present review, almost 70% were from high-income settings. All the studies conducted in low/middle-income settings were single center studies and four were from Brazil. We found no study from Brazil reporting annual incidence rates of opportunistic illnesses. Conclusions: Opportunistic illnesses remain an important public health problem. To better guide health policies in low/middle-income settings, multicenter cohort studies should be encouraged. Studies from Brazil are urgently needed to assess the current burden of opportunistic illnesses in our population and to support the planning of HIV/AIDS health care services organization. Keywords: AIDS-related opportunistic infections, Opportunistic infection, Acquired immunodeficiency syndrome, Incidence

The worldwide elderly population is expected to grow by an additional 694 million people by 2025. By that time, there will be approximately two billion elderly people in the world, most of whom (80%) will be living in developing countries. Based on recent estimates, this population will number over 40 million in 2030 in Brazil and a consequent increase in governmental spending for this population can be expected. Since highly active antiretroviral therapy became available in the mid-1990s, the life expectancy of people living with HIV has increased significantly. Approximately 12 million life years were added to the world between 1996 and 2008 as a consequence of wider access to highly active antiretroviral therapy. In Brazil, the incidence of AIDS among the population aged ≥50 years doubled between 1996 and 2006. The development of antiretroviral therapy has allowed individuals diagnosed at a younger age to live longer, which partially explains the aging tendency associated with the HIV/AIDS epidemic. It is estimated that by 2015, subjects aged ≥50 years will represent 50% of the people living with HIV undergoing clinical treatment. This scenario presents some challenges, including the fact that the diagnosis of HIV tends to be delayed in older patients compared to younger patients because the symptoms of HIV can be confused with those of other common diseases among the elderly and also because healthcare professionals do not consider this population to be at high risk for HIV infection. In regard to the individuals diagnosed with HIV, a further challenge is presented by the morbidity normally associated with aging. Finally, the elderly also exhibit higher susceptibility to the toxic effects and pharmacological interactions of medications. The present article reviews the literature regarding the profile of HIV infection among individuals aged ≥50 years focusing on practical features related to the clinical approach and long-term follow-up of this population. Keywords: HIV, AIDS, Aging, Elderly, Brazil, Comorbidity, HAART

Highly active antiretroviral therapy (HAART) has changed the morbidity pattern affecting HIV-infected individuals to include non-AIDS-defining cancers. We describe the breast cancer cases occurring in a cohort of 860 HIV-infected women followed in Rio de Janeiro, Brazil, and estimate the incidence rate of breast cancer for this population. Nine cases were identified; median age at diagnosis was 46 years. Median survival after breast cancer diagnosis was 12 months. Breast cancer diagnosis was made within 2 to 15 years of HIV-infection diagnosis. At breast cancer diagnosis, CD4 counts ranged from 135 to 782 cells/mm3; six women were receiving HAART. Histological analysis indicated infiltrating ductal carcinoma in all cases. The incidence rate of breast cancer was 133 cases per 100,000 persons-year. Patients from our case series were late diagnosed with breast cancer and thus suffered from worse prognosis. Strategies targeting earlier diagnosis and prompt initiation of treatment are needed. Keywords: HIV, breast neoplasms, case reports, incidence

As lesões intraepiteliais escamosas de alto grau (HSIL) são precursoras do câncer do colo do útero, com maior risco de ocorrência e desenvolvimento em mulheres HIV+. Neste trabalho, estimamos e comparamos o desempenho do exame citológico e da captura híbrida II no rastreamento das lesões precursoras em mulheres HIV+. A população de estudo compreendeu mulheres acompanhadas na coorte prospectiva aberta do Instituto de Pesquisa Clínica Evandro Chagas da Fundação Oswaldo Cruz (IPEC/Fiocruz). A colposcopia e histologia foram consideradas conjuntamente na definição do teste de referência. O exame citológico apresentou sensibilidade de 31,8% e especificidade de 95,5%, enquanto a captura híbrida II apresentou maior sensibilidade (100%) e menor especificidade (52%). As razões de verossimilhança para o teste positivo e negativo foram estimadas em 7,1 e 0,7 para o exame citológico e em 2,1 e 0,0 para a captura híbrida II, respectivamente.