Evaluation from a B-cell epitope-based chimeric protein for the serodiagnosis of tegumentary and visceral leishmaniasis.

The diagnosis of leishmaniasis presents problems due to the variable sensitivity and/or specificity of tests. In addition, high levels of anti-parasite antibodies can remain after treatment, making it difficult to conduct a prognostic follow-up of patients. In this context, it is necessary to identify new candidates to be examined for the sensitive and specific diagnosis of the disease. In the present study, four Leishmania proteins, previously shown as antigenic for tegumentary leishmaniasis (TL), were evaluated, and their linear specific B-cell epitopes were predicted and used to generate a new gene codifying chimeric protein called ChimB, which was cloned, and the recombinant version was expressed, purified, and evaluated in ELISA (Enzyme-Linked Immunosorbent Assay) to diagnose TL and visceral leishmaniasis (VL). A total of 220 human serum samples were used, and, when ChimB was used, results showed sensitivity, specificity, and positive and negative predictive values of 100% for the diagnosis of both diseases; however, when using peptides, the sensitivity values reached from 28.0% to 57.3% and specificity varied from 16.3% to 83.7%. A soluble Leishmania extract (SLA) showed sensitivity and specificity values of 30.7% and 45.9%, respectively. The area under the curve (AUC) value for ChimB was 1.0, while for synthetic peptides, this value reached between 0.502 and 0.635, whereas for SLA, the value was of 0.589. Serological assays using sera samples collected before and after treatment showed significant reductions in the anti-ChimB antibody levels after therapy, suggesting a prognostic role of this recombinant antigen. In conclusion, preliminary data suggest the use from ChimB as a potential candidate for the diagnosis and prognosis of leishmaniasis.

Sensitive and specific serodiagnosis of tegumentary leishmaniasis using a new chimeric protein based on specific B-cell epitopes of Leishmania antigenic proteins.

Serological tests used for the diagnosis of tegumentary leishmaniasis (TL) presents problems, mainly related to their variable sensitivity and/or specificity, which can be caused by low levels of antileishmanial antibodies or by presence of cross-reactive diseases, respectively. In this context, the search for new antigenic candidates presenting higher sensitivity and specificity is urgently required. In the present study, the amino acid sequences of the LiHyT, LiHyD, LiHyV, and LiHyP proteins, which were previously showed to be antigenic in the visceral leishmaniasis (VL), were evaluated and eight B-cell epitopes were predicted and used for construction of gene codifying a chimeric protein called ChimLeish. The protein was expressed, purified and evaluated as a recombinant antigen in ELISA (Enzyme-Linked Immunosorbent Assay) for the diagnosis of TL. The own B cell epitopes used to construct the chimera were synthetized and also evaluated as antigens, as well as a soluble Leishmania braziliensis antigenic extract (SLA). Results showed that ChimLeish presented 100% sensitivity and specificity to diagnose TL, while synthetic peptides showed sensitivity varying from 9.1% to 90.9%, while specificity reached from 98.3% to 99.1%. SLA showed sensitivity and specificity of 18.2% and 98.3%, respectively. A preliminary prognostic evaluation showed that anti-ChimLeish IgG antibodies declined in significant levels, when serological reactivity was compared before and six months after treatment, suggesting also a possible prognostic role of this antigen for TL.

People Living With HIV, Lean Mass, and Sarcopenia: A Systematic Review and Meta-Analysis.

This systematic review aims to estimate the prevalence of sarcopenia in people living with HIV (PLHIV) and to assess whether there is a difference between the muscle mass of PLHIV and people living without HIV. A systematic review of randomized controlled trials, cohort studies, cross-sectional and case-control studies was carried out. PLHIV over 18 years of age and that had their muscle mass evaluated by dual-energy X-ray absorptiometry were included. Overall, 4,376 studies were found, of which 118 had their full texts evaluated. A total of 5,532 people living with HIV and 2,986 people living without HIV were identified in 41 studies. The frequency of sarcopenia defined by low muscle mass (Baumgartner's operational definition) alone was 30.3% (95%CI 24.3%, 37.1%) and the frequency of sarcopenia defined by low muscle mass with low muscle strength (EWGSOP definition) was 4.5% (95%CI 1.3%, 13.9%), p-value = 0.0006. The standardized mean differences of muscle mass between PLHIV and controls was -0.211 units of standard deviation (95%CI -0.419, -0.003). In the meta-regression analysis muscle mass mean difference was associated with BMI, CD4, percentage of subjects on ART, and study design. PLHIV have a lower muscle mass when compared to people living without HIV. This difference appears to be attenuated by higher BMI, CD4 levels, and the percentage of subjects using ART. Furthermore, the frequencies of sarcopenia assessed by the operational definition of Baumgartner and the EWGSOP are not comparable and cannot be interchanged in PLHIV.

Diagnostic application of sensitive and specific phage-exposed epitopes for visceral leishmaniasis and human immunodeficiency virus coinfection.

The diagnosis of visceral leishmaniasis (VL) has improved with the search of novel antigens; however, their performance is limited when samples from VL/human immunodeficiency virus (HIV)-coinfected patients are tested. In this context, studies conducted to identify more suitable antigens to detect both VL and VL/HIC coinfection cases should be performed. In the current study, phage display was performed using serum samples from healthy subjects and VL, HIV-infected and VL/HIV-coinfected patients; aiming to identify novel phage-exposed epitopes to be evaluated with this diagnostic purpose. Nine non-repetitive and valid sequences were identified, synthetized and tested as peptides in enzyme-linked immunosorbent assay experiments. Results showed that three (Pep2, Pep3 and Pep4) peptides showed excellent performance to diagnose VL and VL/HIV coinfection, with 100% sensitivity and specificity values. The other peptides showed sensitivity varying from 50.9 to 80.0%, as well as specificity ranging from 60.0 to 95.6%. Pep2, Pep3 and Pep4 also showed a potential prognostic effect, since specific serological reactivity was significantly decreased after patient treatment. Bioinformatics assays indicated that Leishmania trypanothione reductase protein was predicted to contain these three conformational epitopes. In conclusion, data suggest that Pep2, Pep3 and Pep4 could be tested for the diagnosis of VL and VL/HIV coinfection.

ChimLeish, a new recombinant chimeric protein evaluated as a diagnostic and prognostic marker for visceral leishmaniasis and human immunodeficiency virus coinfection.

Visceral leishmaniasis (VL) is a neglected tropical disease of global importance caused by parasites of the genus Leishmania, and coinfection with human immunodeficiency virus (HIV) is common in countries where both diseases are endemic. In particular, widely used immunological tests for VL diagnosis have impaired sensitivity (Se) and specificity (Sp) in VL/HIV coinfected patients and there is also cross-reactivity with other endemic diseases, e.g., Chagas disease, malaria, and tuberculosis. To develop new antigens to improve the diagnosis of VL and VL/HIV coinfection, we predicted eight specific B-cell epitopes of four Leishmania infantum antigens and constructed a recombinant polypeptide chimera antigen called ChimLeish. A serological panel of 195 serum samples was used to compare the diagnostic capabilities of ChimLeish alongside the individual synthetic peptides. ChimLeish reacted with sera from all VL and VL/HIV coinfected patients [Se = 100%; Sp = 100%; area under the curve (AUC) = 1.0]. Peptides showed lower reactivities (Se = 76.8 to 99.2%; Sp = 67.1 to 95.7%; AUC between 0.87 and 0.98) as did a L. infantum antigenic preparation used as an antigen control (Se = 56.8%; Sp = 69.5%: AUC = 0.45). Notably, ChimLeish demonstrated a significant reduction (p < 0.05) of anti-ChimLeish antibodies after treatment and cure of a small number of patients. Although only a limited serological panel was tested, preliminary data suggest that ChimLeish should be evaluated in larger sample studies for the diagnosis of VL and VL/HIV coinfection.

Biotechnological applications from a Leishmania amastigote-specific hypothetical protein in the canine and human visceral leishmaniasis.

The treatment against visceral leishmaniasis (VL) presents problems, mainly related to the toxicity and/or high cost of the drugs. In this context, a rapid and precise diagnosis of the disease should be performed, mainly to treat patients as soon as possible, aiming to reduce the treatment time and the toxicity of the therapeutics. In the present study, the diagnostic role of an amastigote-specific Leishmania protein was evaluated in the canine and human VL. Results showed that the recombinant protein (called rLiHyJ) and one specific B cell epitope (called PeptJ) predicted from protein sequence presented high sensitivity and specificity values to diagnose canine and human disease, showing also a low reactivity against cross-reactive samples. The rA2 protein and a parasite antigenic extract showed variable sensitivity and/or specificity values in the ELISA experiments. A prognostic evaluation of protein and peptide in the human VL indicated that specific IgG antibodies significantly decreased after treatment, when compared to be values obtained before therapy. The in vitro immunogenicity using rLiHyJ in peripheral blood mononuclear cell (PBMC) cultures collected of such patients and healthy subjects suggested that the protein induced lymphoproliferation and high IFN-γ production in the stimulated cells. In conclusion, although preliminary, results suggest that rLiHyJ and PeptJ could present distinct biotechnological applications in the canine and human VL.

Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

An immunoproteomics approach to identify Leishmania infantum proteins to be applied for the diagnosis of visceral leishmaniasis and human immunodeficiency virus co-infection.

The co-infection between visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) has increased in several countries in the world. The current serological tests are not suitable since they present low sensitivity to detect the most of VL/HIV cases, and a more precise diagnosis should be performed. In this context, in the present study, an immunoproteomics approach was performed using Leishmania infantum antigenic extracts and VL, HIV and VL/HIV patients sera, besides healthy subjects samples; aiming to identify antigenic markers for these clinical conditions. Results showed that 43 spots were recognized by antibodies in VL and VL/HIV sera, and 26 proteins were identified by mass spectrometry. Between them, ß-tubulin was expressed, purified and tested in ELISA experiments as a proof of concept for validation of our immunoproteomics findings and results showed high sensitivity and specificity values to detect VL and VL/HIV patients. In conclusion, the identified proteins in the present work could be considered as candidates for future studies aiming to improvement of the diagnosis of VL and VL/HIV co-infection.

Lipid Accumulation Product Index to Predict Metabolic Syndrome in People Living with HIV.

BACKGROUND: Dyslipidemia and central obesity are the main components of metabolic syndrome, which represent important risk factors for cardiovascular diseases in people living with human immunodeficiency virus (HIV). The lipid accumulation product (LAP) index has been shown in studies as an efficient marker of metabolic syndrome in general adult population and its applicability in HIV-infected population is not discussed. We aimed to assess the accuracy of the LAP index to identify metabolic syndrome in people living with HIV. METHODS: It is a cross-sectional study with 141 HIV-infected patients on antiretroviral therapy, conducted in a reference centre of infectious diseases in southeast Brazil. Evaluations included LAP index, anthropometric measurements and clinical and laboratorial variables. Metabolic syndrome was defined by International Diabetes Federation (IDF) criteria. RESULTS: The prevalence of metabolic syndrome in our sample was 10.6%. A positive and significant correlation was found between the metabolic syndrome and LAP (r=0.401; P<0.01), metabolic syndrome and body mass index (r=0.361; P<0.01) and metabolic syndrome and waist circumference (r=0.427; P<0.01) in our sample. The analysis of the receiver-operating characteristic (ROC) curve revealed that the best cut-off value for LAP index to define metabolic syndrome was 59.4 (sensitivity 80%, specificity 79% and area under the curve (AUC) of 0.875. In female and male, analysis of the ROC curve revealed that the best cut-off value for LAP index to define metabolic syndrome was 56.3 (sensitivity 100%, specificity 82% and AUC of 0.929) and 52.0 (sensitivity 78%, specificity 74% and AUC of 0.838), respectively. CONCLUSION: Despite the low prevalence of metabolic syndrome in our sample, the ROC curves analyzes demonstrated a good diagnostic accuracy as an additional screening tool of metabolic syndrome according to the IDF.

Recombinant Leishmania eukaryotic elongation factor-1 beta protein: A potential diagnostic antigen to detect tegumentary and visceral leishmaniasis in dogs and humans.

The laboratorial diagnosis of leishmaniasis is based on parasitological methods, which are invasive, present high cost, require laboratorial infrastructure and/or trained professionals; as well as by immunological methods, which usually present variable sensitivity and/or specificity, such as when they are applied to identify asymptomatic cases and/or mammalian hosts presenting low levels of antileishmanial antibodies. As consequence, new studies aiming to identify more refined antigens to diagnose visceral (VL) and tegumentary (TL) leishmaniasis are urgently necessary. In the present work, the Leishmania eukaryotic elongation factor-1 beta (EF1b) protein, which was identified in L. infantum protein extracts by antibodies in VL patients' sera, was cloned and its recombinant version (rEF1b) was expressed, purified and tested as a diagnostic marker for VL and TL. The post-therapeutic serological follow-up was also evaluated in treated and untreated VL and TL patients, when anti-rEF1b antibody levels were measured before and after treatment. Results showed that rEF1b was highly sensitive and specific to diagnose symptomatic and asymptomatic canine VL, as well as human TL and VL. In addition, low cross-reactivity was observed when sera from healthy subjects or leishmaniasis-related diseases patients were tested. The serological follow-up showed also that rEF1b-specific antibodies declined significantly after treatment, suggesting that this protein could be also evaluated as a prognostic marker for human leishmaniasis.

Estimating time-varying epidemiological parameters and underreporting of Covid-19 cases in Brazil using a mathematical model with fuzzy transitions between epidemic periods.

Our study conducts a comprehensive analysis of the Covid-19 pandemic in Brazil, spanning five waves over three years. We employed a novel Susceptible-Infected-Recovered-Dead-Susceptible (SIRDS) model with a fuzzy transition between epidemic periods to estimate time-varying parameters and evaluate case underreporting. The initial basic reproduction number (R0) is identified at 2.44 (95% Confidence Interval (CI): 2.42-2.46), decreasing to 1.00 (95% CI: 0.99-1.01) during the first wave. The model estimates an underreporting factor of 12.9 (95% CI: 12.5-13.2) more infections than officially reported by Brazilian health authorities, with an increasing factor of 5.8 (95% CI: 5.2-6.4), 12.9 (95% CI: 12.5-13.3), and 16.8 (95% CI: 15.8-17.5) in 2020, 2021, and 2022 respectively. Additionally, the Infection Fatality Rate (IFR) is initially 0.88% (95% CI: 0.81%-0.94%) during the initial phase but consistently reduces across subsequent outbreaks, reaching its lowest value of 0.018% (95% CI: 0.011-0.033) in the last outbreak. Regarding the immunity period, the observed uncertainty and low sensitivity indicate that inferring this parameter is particularly challenging. Brazil successfully reduced R0 during the first wave, coinciding with decreased human mobility. Ineffective public health measures during the second wave resulted in the highest mortality rates within the studied period. We attribute lower mortality rates in 2022 to increased vaccination coverage and the lower lethality of the Omicron variant. We demonstrate the model generalization by its application to other countries. Comparative analyses with serological research further validate the accuracy of the model. In forecasting analysis, our model provides reasonable outbreak predictions. In conclusion, our study provides a nuanced understanding of the Covid-19 pandemic in Brazil, employing a novel epidemiological model. The findings contribute to the broader discourse on pandemic dynamics, underreporting, and the effectiveness of health interventions.

Transmitted human immunodeficiency virus-1 drug resistance in a cohort of men who have sex with men in Belo Horizonte, Brazil--1996-2012.

The presence of transmitted human immunodeficiency virus (HIV)-1 drug-resistance (TDR) at the time of antiretroviral therapy initiation is associated with failure to achieve viral load (VL) suppression. Here, we report TDR surveillance in a specific population of men who have sex with men (MSM) in Belo Horizonte, Brazil. In this study, the rate of TDR was evaluated in 64 HIV-infected individuals from a cohort of MSM between 1996-June 2012. Fifty-four percent had a documented recent HIV infection, with a seroconversion time of less than 12 months. The median CD4+T lymphocyte count and VL were 531 cells/mm3 and 17,746 copies/mL, respectively. Considering the surveillance drug resistance mutation criteria, nine (14.1%) patients presented TDR, of which three (4.7%), five (7.8%) and four (6.2%) had protease inhibitors, resistant against nucleos(t)ide transcriptase inhibitors and against non-nucleoside reverse-transcriptase inhibitors mutations, respectively. Two of the patients had multi-drug-resistant HIV-1. The most prevalent viral subtype was B (44, 68.8%), followed by subtype F (11, 17.2%). This study shows that TDR may vary according to the population studied and it may be higher in clusters of MSM.

Suppression of HIV in the first 12 months of antiretroviral therapy: a comparative analysis of dolutegravir- and efavirenz-based regimens.

OBJECTIVE: To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. METHODS: We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. RESULTS: Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. CONCLUSION: Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered.

Misinformation Caused Increased Urban Mobility and the End of Social Confinement Before the Second Wave of COVID-19 in Amazonia.

Tendentious projections about COVID-19 in Brazil provided an appealing excuse for individuals and decision-makers to justify poor choices during a critical phase of the pandemic. The erroneous results likely contributed to premature resumption of in-person school classes and easing of restrictions on social contact, favoring the resurgence of COVID-19. In Manaus, the largest city in the Amazon region, the COVID-19 pandemic did not end in 2020 of its own accord, but rather rebounded in a disastrous second wave of the disease.

Violence, discrimination, and sexual health practices among adolescent men who have sex with men, transgender women and travestis in three cities in Brazil.

The HIV epidemic has a disproportionate impact on adolescent and young men who have sex with men (AMSM) and transgender women and travestis (ATGW), with an increased HIV prevalence over the last 10 years. Violence affects the lives of these populations, undermining their ability to self-care and making them more vulnerable to HIV infection. In this study, we aimed to examine the association between different types of victimization by violence and discrimination and sexual health practices of these adolescent populations in steady and casual relationships. We conducted a cross-sectional study using baseline data from the cohort of PrEP1519 project. We used the mean score of sexual health practices as our outcome and the cumulative score of discrimination (within family, community, education, religious, online and public spaces) and violence (physical, sexual and intimate partner) as our exposure variable. We performed linear regression analyses to estimate the association between exposure and outcome. We found that 90% of AMSM and 95% of ATGW experienced at least one form of violence in the three months prior to this study and about 45% of ATGW suffered sexual violence during the same period. Experiencing discrimination within healthcare settings (from facilities or providers) was negatively associated with sexual health practices. Discrimination and violence negatively affect sexual health practices. HIV prevention and care of AMSM and ATGW people should involve listening to their experiences and addressing discrimination and violence in this population.

When Ethics and the Law Collide: A Multicenter Demonstration Cohort Study of Pre-Exposure Prophylaxis Provision to Adolescent Men Who Have Sex With Men and Transgender Women in Brazil.

PURPOSE: To explore legal and ethical challenges related to adolescents' participation in human immunodeficiency virus (HIV) research that may affect their best interests. METHODS: We analyzed the ethical principles and legal aspects of the participation of 15-17-year-old men who have sex with men and transgender women in the pre-exposure prophylaxis (PrEP) 1519 study, a PrEP demonstration cohort study in three Brazilian cities. The analyses of ethics review committees' (ERCs) evaluations and court decisions followed ethical and human rights principles. An HIV vulnerability score was created, and descriptive statistics and multivariate logistic regression were performed using data from 347 participants. RESULTS: The ERCs evaluated the benefits and risks of research participation, all finding that the benefits outweighed the risks. ERCs deferred responsibility for decisions about waiving parental consent to the judiciary. State courts reached different decisions about waiving parental consent, reflecting variation in recognition of adolescents' evolving capacities and the adolescent as a subject of sexual rights and the primary agent capable of deciding on their health and best interests. The most vulnerable adolescent participants were found in sites where the blanket waiver was in place. DISCUSSION: Judicializing the ethical review process is detrimental to fulfilling the ethical principle of justice and vulnerable adolescents' access to health research. ERCs must be sufficiently independent and autonomous and have the capacity to respect, protect, and help fulfill the rights of participants while ensuring the generation of adequate evidence to inform public health practice.

When prevention is the best remedy: HIV pre-exposure prophylaxis (PrEP) among adolescents gays and transgender women in Belo Horizonte, Minas Gerais State, Brazil.

Based on the incorporation of pre-exposure prophylaxis (PrEP) as an HIV prevention strategy and considering the need to comprehend the use of medication among young people, this article analyzes narratives of gay men and transgender women from Belo Horizonte, Minas Gerais State, Brazil, participating in the PrEP1519 study. This is a qualitative research, based on the interpretative anthropology, developed by 10 in-depth interviews with PrEP users followed-up for at least three months between October and November 2019. The results showed that the drug was seen as the main motivation for participating in the study and as a strategy combined with the use of condoms, whether as additional prevention, or assuming the leading role. The medication revealed signs built by the gender performances and their relation to other medications, especially the experience of trans girls in hormonal therapy. Regarding the socialization of the use of PrEP, the narratives showed that there was no secret between the couples, which did not meant that stigmas on the association with HIV did not exist, mainly in the virtual context. In the family environment, they reported questions about the preventive function of the medication and the voluntary nature of the participation in the study. The youth's narratives revealed plural meanings of the medication and its social use, composing both the boys' and girls' performances. The signs attributed to the medication indicated that in addition to maintenance of health, the medication improves life and sexual freedom.

RT-qPCR-based pool testing for the diagnosis of COVID-19.

This study proposes a strategy for large-scale testing among a large number of people for the early diagnosis of COVID-19 to elucidate the epidemiological situation. Pool testing involves the analysis of pooled samples. This study aimed to discuss a reverse transcription technique followed by quantitative real-time polymerase chain reaction using pool testing to detect SARS-CoV-2 in nasopharyngeal swab samples. The study proposes an innovative diagnostic strategy that contributes to resource optimization, cost reduction, and improved agility of feedback from results. Pool testing is simultaneously performed on multiple samples to efficiently and cost-effectively detect COVID-19. Pool testing can optimize resource utilization and expand diagnostic access, and is a viable alternative for developing countries with limited access to testing. To optimize resources, the pool size was determined by estimating COVID-19 prevalence in the study population.

Adherence, Safety, and Feasibility of HIV Pre-Exposure Prophylaxis Among Adolescent Men Who Have Sex With Men and Transgender Women in Brazil (PrEP1519 Study).

PURPOSE: To evaluate the adherence, safety, and feasibility of pre-exposure prophylaxis (PrEP) in real-world settings among adolescent men who have sex with men (AMSM) and transgender women (ATGW). METHODS: PrEP1519 is a single-arm, multicentric demonstration cohort study of daily oral PrEP among AMSM and ATGW aged 15 to 19 years in Brazil. Study visits occurred at baseline, weeks 4, 12, and then quarterly until 96 weeks. Descriptive statistics and a mixed logistic model for longitudinal data evaluated the factors associated with high adherence. RESULTS: One thousand sixteen AMSM and ATGW accessed the PrEP1519 clinics. Of those, 998 (98.2%) underwent clinical triage. Forty one were diagnosed with human immunodeficiency viruses (HIV) at baseline (4.0%) and 79 (7.9%) were not eligible for PrEP. Of the 878, 795 (90.5%) enrolled in PrEP, 82 (10.3%) were lost to follow-up, and 713 were included. There was no significant decrease in creatinine clearance; only two participants had grade-III aspartate aminotransferase elevation. Incident HIV infection occurred in eight participants (incidence rate [IR] = 1.64 per 100 person-years [PY]): two in 15-17 years (IR = 2.24 per 100 PY) and six in 18-20 years (IR = 1.51 per 100 PY). PrEP adherence was higher among those with more years of schooling, those reporting no difficulties in PrEP use due to side effects, and who had low HIV risk perception in the past three months. DISCUSSION: PrEP for AMSM and ATGW was safe and feasible in real-world settings. However, a higher IR among young adolescents and a higher adherence among less vulnerable people indicate the need for greater care, considering the specificities of this age group.