Proviral Quasispecies Diversity Is Not Associated With Virologic Breakthrough or CD4+ T Cell Loss in HIV-1 Elite Controllers

Elite controllers (EC) are able to control HIV-1 replication to extremely low levels (<50 HIV-1 RNA copies/mL) in the absence of antiretroviral therapy. However, some EC experience CD4+ T cell loss and/or lose their ability to control HIV-1 over the course of infection. High levels of HIV-1 env proviral diversity, activated T cells and proinflammatory cytokines were pointed out as relevant biomarkers for detection of EC at risk of virologic/immunologic progression. The aim of this study was to assess the importance of proviral diversity as a prognostic marker of virologic and/or immunologic progression in EC. To this end, we analyzed plasma viremia, total HIV DNA levels, T cells dynamics, and activation/inflammatory biomarkers in EC with low (ECLD = 4) and high (ECHD = 6) HIV-1 env diversity. None of ECLD and ECHD subjects displayed evidence of immunologic progression (decrease in absolute and percentage of CD4+ T cells) and only one ECHD subject presented virologic progression (≥2 consecutive viral loads measurements above the detection limit) 2–5 years after determination of proviral env diversity. Despite differences in proviral genetic diversity, the ECLD and ECHD subgroups displayed comparable levels of total cell-associated HIV DNA, activated CD8+ T (CD38+HLA-DR+) cells and plasmatic inflammatory biomarkers (IP-10, IL-18, RANTES, PDGF-AA, and CTACK). These results indicate that the genetic diversity of the HIV-1 proviral reservoir is not a surrogate marker of residual viral replication, immune activation or inflammation, nor an accurate biomarker for the prediction of virologic breakthrough or CD4+ T cells loss in EC

Plasmatic Levels of IL-18, IP-10, and Activated CD8+ T Cells Are Potential Biomarkers to Identify HIV-1 Elite Controllers With a True Functional Cure Profile

Elite controllers (ECs) are rare individuals able to naturally control HIV-1 replication below the detection limit of viral load (VL) commercial assays. It is unclear, however, whether ECs might be considered a natural model of a functional cure because some studies have noted CD4+ T cell depletion and disease progression associated with abnormally high levels of immune activation and/or inflammation in this group. Here, we propose the use of immunological parameters to identify HIV-1 ECs that could represent the best model of a functional cure. We compared plasma levels of six inflammatory biomarkers (IP-10, IL-18, sCD163, sCD14, CRP, and IL-6) and percentages of activated CD8+ T cells (CD38+HLA-DR+) between 15 ECs [8 with persistent undetectable viremia (persistent elite controllers) and 7 with occasional viral blips (ebbing elite controllers)], 13 viremic controllers (VCs—plasma VL between 51 and 2,000 RNA copies/mL), and 18 HIV-1 infected patients in combined antiretroviral therapy, with suppressed viremia, and 18 HIV-uninfected controls (HIV-neg). The two groups of ECs presented inflammation and activation profiles similar to HIV-neg individuals, and there was no evidence of CD4+ T cell decline over time. VCs, by contrast, had higher levels of IL-18, IP-10, and CRP and a lower CD4/CD8 ratio than that of HIV-neg (P < 0.05). Plasma levels of IL-18 and IP-10 correlated positively with CD8+ T cell activation and negatively with both CD4/CD8 and CD4% in HIV-1 controllers. These results suggest that most ECs, defined using stringent criteria in relation to the cutoff level of viremia (≤50 copies/mL) and a minimum follow-up time of >5 years, show no evidence of persistent inflammation or immune activation. This study further suggests that plasmatic levels of IL-18/IP-10 combined with the frequency of CD8+CD38+HLA-DR+ T cells can be important biomarkers to identify models of a functional cure among HIV-1 ECs

Agricultural Research Service Weed Science Research: Past, Present, and Future

The U.S. Department of Agriculture-Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed-crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America\u27s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency\u27s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section

Avaliação da resposta terapêutica de 272 pacientes com Leishmaniose Tegumentar Americana tratados com baixas doses de antimônio pentavalente

Made available in DSpace on 2018-08-06T13:15:00Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) brenda_r_s_hoagland_ipec_pcdi_mest_2006: 542949 bytes, checksum: ef11cdbba8c2ce3258a7406ff786ade8 (MD5) Previous issue date: 2006Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.A Leishmaniose é uma doença infecto-parasitária endêmica em 88 países de 4 continentes. Mais de 90% doscasos cutâneos ocorrem no Irã, Afeganistão, Arábia Saudita, Brasil e Peru, segundo dados da Organização Mundial de Saúde (OMS) (World Health Organization, 1998). Nos últimos anos o Brasil tem registrado média anual de 35 mil novos casos de Leishmaniose Tegumentar Americana (LTA). (Ministério da Saúde, Secretaria de Vigilância em Saúde et al., 2003). Neste trabalho foi realizado um estudo do tipo série de casos, de acompanhamento longitudinal, com o objetivo de avaliar a eficácia do uso de baixas doses de antimônio, em diferentes esquemas terapêuticos, para o tratamento das formas cutânea (LC) e mucosa (LM) de Leishmaniose Tegumentar Americana (LTA). Foram incluídos 272 pacientes diagnosticados com LTA, atendidos no período entre 1º de janeiro de 1998 e 31 de dezembro de 2004 no Centro de Referência em Leishmanioses do Instituto Nacional de Infectologia Evandro Chagas (VigiLeish/IPEC). Deste total de pacientes, 201 apresentavam LC e 71 com LM, sendo 173 (64%) homens e 99 mulheres (36%), cujas idades variaram entre 2 e 92 anos A escolha dos esquemas terapêuticos (contínuo, em séries e intralesional) foi definida de acordo com as características clínicas de cada paciente, como: idade, presença de co-morbidades, medicação concomitante e forma clínica da LTA. Todos foram tratados com doses de 5mg/Kg/dia de antimoniato de meglumina, exceto nos casos tratados por via intralesional, nos quais o volume necessário variou de acordo com o tamanho e o número de lesões. Nos pacientes com LC, a taxa epitelizaçãoapós primeiro tratamento com os esquemas terapêuticos contínuo, em séries e intralesional foram, respectivamente, de 92% (n=154), 94% (n=33) e 70% (n=10). Nos pacientes com LM, tratados com esquema contínuo e em séries, a taxa de epitelizaçãofoi de, respectivamente, 74% (n=53) e 81% (n=16). Esses pacientes não foram tratados com esquema intralesional devido à dificuldade de administração do medicamento neste tipo de lesão Foi realizado um segundo tratamento em 51 pacientes por reativação ou abandono do primeiro. Destes, 33 apresentavam LC e 18 LM. O antimônio foi novamente utilizado em 48 deles. Quinze pacientes reativaram, 10 com LC e 5 com LM, sendo indicado um terceiro tratamento. O antimônio foi utilizado em 4 pacientes com LC e 2 com LM. Apenas 1 paciente, com LM, necessitou de um quarto tratamento, após três reativações com antimônio, curando-se neste último, com anfotericina B. A eficácia do tratamento com baixas doses de antimônio, tanto nos casos de LC quanto de LM, associada à baixa freqüência e intensidade dos efeitos adversos, possibilitou o tratamento ambulatorial de pacientes idosos ou com outras co-morbidades, que necessitariam de hospitalizaçãoou receberiam contra-indicação ao tratamento convencional com 20mg Sb/Kg/diaLeishmaniasis is an endemic infectious diseases in 88 countries from 4 continents. More then 90% of tegumentar cases are from Iran, Afghanistan, Saudi Arabia, Brazil and Peru, according to WHO (World Health Organization, 1998). On the last years, Brazil has registered annually 35.000 new cases of American Tegumentar Leishmaniasis (ATL), according to Brazilian Health Governmental (2003). An observational series of cases studies was performed, aiming at evaluating the efficacy of low doses of antimonium in different therapeutic regimens for the treatment of cutaneous and mucosal presentations (CP and MP, respectively) of ATL. A total of 272 patients with diagnosis of ATL were included, treated between January 1st, 1998 and December 31st, 2004 at Laboratório de Vigilância em Leishmanioses [ Leishmaniasis Vigilance Lab at Evandro Chagas Clinical Research Institute] (VigiLeish/IPEC). From these patients, 201 had CP and 71 had MP. This population was composed by 173 (64%) men and 99 (36%) women, ranging from 2-92 years The choice of therapeutic regimens (continuous, in series or intralesional) was determined according to the clinical characteristics of each patient, such as: age, presence of co-morbidities, concomitant medications and clinical presentation of ATL. All patients were treated with meglumine antimoniate 5mg/kg/day, but the cases treated via intralesional, in which the volume required ranged according to the number and the extension of the lesions. In patients with CP, epithelization rate after the first treatment with continuous, in series and intralesional regimens were 92% (N=154), 94% (N=33), and 70% (N=10), respectively. In patients with MP treated with continuous and in series regimens, epithelization rate was 74% (N=53) e 81% (N=16), respectively. These patients were not treated with intralesional regimen due to difficulties related to the application of the drug in this type of lesion A second treatment was performed in 51 patients, due to reactivation or discontinuation of first regimen. Among these, 33 had CP and 18 had MP. Antimonium was used again to 48 patients, of which 15 reactivated the disease (10 had CP and 5 had MP), a third therapeutic regimen being required, where antimonium was used to 4 patients with CP and 2 with MP. Only one patient required a forth treatment, after three reactivations with antimonium, with resolution after treatment with amphotericin B. The efficacy of low doses antimonium regimens, both in CP and in MP, associated with the low frequency and intensity of the adverse events presented, made possible outpatient treatment of elderly patients, as well as patients presenting other co-morbidities, who would require in-hospital treatment or for whom standard treatment with 20mg Sb/kg/day would be contraindicate

Conhecimento, interesse, decisão sobre o uso e adesão precoce à profilaxia pré-exposição (PrEP) entre homens que fazem sexo com homens (HSH) e mulheres transexuais (Trans) participantes no estudo PrEP Brasil

Made available in DSpace on 2018-05-21T13:34:22Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) brenda_hoagland_ini_dout_2017.pdf: 3221243 bytes, checksum: 77e45843d010057caf11d805714186c6 (MD5)Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Introdução: A profilaxia pré-exposição (PrEP) utilizando a combinação de dois antirretrovirais, o disoproxil fumarato de tenofovir (TDF) e emtricitabina (FTC), por via oral tem se mostrado eficaz na prevenção do HIV em homens que fazem sexo com homens (HSH) com alto risco de aquisição da infecção. O Brasil apresenta a maior população da América Latina vivendo com HIV/AIDS e uma epidemia concentrada em HSH com uma prevalência de 14,2% quando comparado a população geral, que é de 0,6%. A população jovem de HSH são quase 40% dos casos de AIDS, com um aumento de 41,3% (entre 15-19 anos) e 25,1% (entre 20-24 anos) entre 2004 e 2013. Apesar da população de mulheres transexuais (Trans) representarem uma parcela menor que os HSH, elas apresentam índices extremamente elevados de risco e diagnóstico de infecção pelo HIV. Deste modo a epidemia de HIV persiste sem decréscimo entre HSH e Trans, com uma elevada proporção desses indivíduos desconhecendo sua condição sorológica. Neste contexto, foi desenhado o PrEP Brasil (NTC01989611), um estudo multicêntrico, aberto, de demonstração de PrEP para acessar a intenção de uso, viabilidade e segurança de oferecer PrEP no Sistema Único de Saúde (SUS) para a população de HSH e Trans de alto risco para o HIV. Objetivo: Descrever o conhecimento, o interesse e a decisão sobre o uso e a adesão precoce à PrEP entre HSH e Trans, através dos níveis de TDF/FTC medidas em amostras de sangue seco (DBS) coletadas na visita de semana 4 e seus fatores associados no estudo demostrativo PrEP Brasil Primeiro Artigo: Descrever o conhecimento e interesse da PrEP entre HSH e TRANS participantes do PrEP Brasil. Conhecimento e interesse para usar PrEP assim como outros métodos de prevenção foram dados na forma de percentuais. Modelos de regressão logística foram usados para explorar e quantificar os fatores associados ao conhecimento e aceitabilidade de PrEP. Variáveis com p < 0.1 na análise bivariada foram incluídos nos modelos ajustados iniciais. O modelo ajustado final incluiu variáveis que persistiram significantes (no limite de 5% da significância) assim como as variáveis que foram consideradas de confusão (qualquer uma que modificasse o odds ratio estimado em mais que 10%). A prevalência do HIV foi calculada excluídos os casos faltantes (n=52 não realizou teste rápido do HIV). Segundo Artigo: Descrever a decisão de uso e a adesão precoce a PrEP entre HSH e mulheres transexuais através da medição dos níveis séricos de Tenofovir e Emtricitabina em amostras de sangue seco coletadas em papel de filtro (DBS) na semana 4 do estudo PrEP Brasil, assim como seus fatores associados. Também foram descritas as características demográficas e de risco da população incluída no estudo. Variáveis descrevendo as características dos indivíduos potencialmente elegíveis (incluídos e não incluídos), assim como por centro de estudo que o participante foi incluído foi apresentado em números absolutos e proporções. As distribuições foram comparadas usando análises de qui-quadrado e Kruskal-Wallis. A decisão de usar PrEP foi definida como o número de participantes incluídos dividido pelo número de participantes potencialmente elegíveis na pré-triagem menos aqueles clinicamente inelegíveis (nas vistas de triagem e inclusão) Os preditores dos níveis de TDF/FTC foram acessados utilizando modelos de regressão logística ordinal. Apenas variáveis estatisticamente significantes a 5% no modelo não ajustado foram mantidas no modelo ajustado. Os resultados foram reportados como odds ratio, que podem ser interpretados como o efeito no odds sendo a categoria dos níveis de drogas mais altos versus os mais baixos. A associação de sintomas gastrointestinais e os níveis de drogas, medidos na visita de semana 4, foram também analisados usando modelos de regressão logística ordinal. Adicionalmente, para explorar possíveis efeitos do uso de hormônios nos níveis de TFV-DP em Trans, foram feitas duas abordagens de modelagens, ode foi usado: 1) modelo de regressão logística usando \22654 doses/semana como resultado e uso/não-uso de hormônios como a variável dicotômica explanatória, 2) modelo de regressão logística linear com concentrações de TVF-DP como a variável contínua de resultado e uso/não-uso de hormônios como a variável dicotômica explanatória. As análises foram feitas usando o PROC GENMOD disponível no Software SAS e a suposição de odds proporcional foi verificada através do Teste de Pontuação. Conclusões: O estudo mostrou que a aceitabilidade e o interesse pela PrEP foi elevada entre HSH e mulheres transexuais e associada a comportamentos sexuais de alto risco para infecção pelo HIV, indicando que estes indivíduos estão interessados em novas estratégias de prevenção. Os resultados sugerem que a PrEP pode ser implementada com sucesso no Sistema Único de Saúde brasileiro para esta população específica. A elevada proporção de indivíduos com alcançaram níveis séricos protetores de TDF/FTC é encorajador e a alta adesão a PrEP sugere que esta pode ser uma estratégia eficaz na redução da infecção pelo HIV entre HSH e Trans em nosso meio.Introduction: Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC),has been shown to be efficacious for HIV prevention for high-risk men who have sex with men (MSM). Brazil has the largest population of individuals living with HIV/AIDS in Latin America, and a concentrated epidemic with an estimated HIV prevalence of 0.6% in the general population and 14.2% prevalence among MSM. Young MSM account for nearly 40% of AIDS cases, with an increase of 41.3% (aged 15-19 years) and 25.1% (aged 20-24 years) observed in this group from 2004 to 2013. Although transgender women (Trans) represent a smaller population than MSM, they have extremely elevated HIV infection rates and very high risk for HIV infection. Thus, the HIV epidemic in Brazil persists unabated in MSM and Trans, with a high proportion of individuals remaining unaware of their HIV status. In this context, the PrEP Brasil Study (NCT01989611), a multicenter, open-label, PrEP demonstration project, was designed to assess uptake, safety and feasibility of PrEP provided for high risk MSM and Trans through the Brazilian public health system (Sistema Único de Saúde- SUS). Objective: Describe PrEP awareness, willingness, uptake, early adherence and its associated factors among MSM and Trans, as well as describe TDF/FTC drug levels measured in dried blood spots (DBS) at week 4 and its associated factors in the PrEP Brasil demonstration study. Also, we describe baseline demographic and risk characteristics of the study population First Article: Describe PrEP awareness and willingness, also its associated factors among MSM and Trans participants from PrEP Brasil Study. Awareness and willingness to use PrEP as well as other HIV prevention measures are given as percentages. Logistic regression models were used to explore and quantify the association of factors with PrEP awareness and willingness. Variables with p<0.1 in bivariate analysis were included in the initial adjusted models. The final adjusted models included variables that remained significant (at 5% significance threshold) as well as variables that were considered confounders (i.e., those that changed the odds ratio estimate of any of the remaining variables by more than 10%). The prevalence of HIV was calculated excluding missing cases (HIV rapid test \2018not performed\2019, n=52). Second Article: Describe PrEP Uptake and Early Adherence among HSH and transgender women using TDF/FTC drug levels measured in dried blood spots (DBS) at week 4 and its associated factors, as well as describe baseline demographic and risk characteristics of the study population in the PrEP Brasil demonstration study. Variables describing the characteristics of potentially eligible individuals (enrolled and not enrolled), as well as enrolled participants by site location are presented in terms of absolute numbers and proportions distributions were compared using chi-square statistics or Kruskal-Wallis. PrEP uptake was defined as the number of participants enrolled divided by the number of potentially eligible at the pre-screening minus the clinical ineligible (at screening and enrollment visit. Predictors of drug levels were assessed using ordinal logistic regression models Only variables statistically significant xi at 5% in the unadjusted model were kept in the adjusted model. The results are reported in terms of odds ratio, which can be interpreted as the effect of the variable on the odds of being in a higher versus lower category of drug levels. The association of GI symptoms and drug levels, both measured at week 4 was also evaluated using ordinal logistic regression models. Additionally, to explore possible effects of hormone use on TFV-DP levels among Trans, two modeling approaches were used: 1) a logistic regression model with \22654 doses/week as the outcome and use/non-use of hormone as the dichotomous explanatory variable, 2) a linear regression model with TFV-DP concentration as the continuous outcome variable and use/non-use of hormone as the dichotomous explanatory variable. Analyses were performed using PROC GENMOD available in the Software SAS and the assumption of proportional odds was checked using the Score test. Conclusions: The study showed that PrEP acceptability and willingness was high among MSM and transgender women and its association with riskier behavior is reassuring as it indicates that those individuals who are at higher risk of HIV infection are interested in this new prevention strategy. Our results show that PrEP for high risk MSM and trans women can be successfully delivered in the context of the Brazilian Public Health System. The high proportion of participants achieving protective drug levels is encouraging. Moreover, high PrEP early adherence suggests that PrEP use may be an effective strategy to reduce HIV infection among MSM in our settin

Development and Perceptions of an Academic Success Tool for Pharmacy Students

Objective: Some students may face challenges with graduate-level reading and writing, particularly in certain active learning pedagogies, such as team-based learning or peer instruction, which require extensive pre-reading. The objective of this study is to determine the perceived utility of an academic literacy (reading/writing) test for first professional year student pharmacists (P1s). Methods: In a collaboration between pharmacy and linguistics faculty, an academic literacy assessment tool was developed using fall P1 course materials. After pilot testing and adjustments, the revised test was administered to all P1 students by trained facilitators, then scored. Students needing literacy support were identified, met with individually to debrief on the assessment, and offered a year-long, one-on-one tutoring program. P1 faculty participated in an end-of-semester focus group session to determine whether the assessment correctly identified students who benefited from literacy support, and to decide on the impact of subsequent support. Thematic analysis was performed on the data. Results: A total of 13 students were identified as at-risk through the assessment. Since tutoring was optional, eight students met at least once, and two students met weekly during the ensuing semester. Faculty from the end-of-semester focus group 1) stated that the assessment accurately pre-identified students who struggled with literacy components of P1 coursework, and 2) expressed a wish for earlier identification of students with required instead of optional tutoring. Conclusions: Faculty perceived that the tool accurately identified students, but the timing and the volunteer nature of the follow-up tutoring limited the success of the assessment effort

Pre-exposure prophylaxis use, HIV knowledge, and internalized homonegativity among men who have sex with men in Brazil: A cross-sectional study.

BackgroundPre-exposure prophylaxis (PrEP) use in Brazil remains low despite free national access. We explored associations of HIV knowledge and internalized homonegativity with PrEP use among PrEP-eligible men who have sex with men (MSM).MethodsBrazilian Hornet users completed an online, cross-sectional survey in February-March 2020. We included cis-men ≥18 years old who reported recent sex with men and were PrEP-eligible per the following: condomless anal intercourse, partner(s) living with HIV, transactional sex, and/or sexually transmitted infection. Our outcome was current PrEP use, defined by the response, "I am currently taking PrEP." Key predictors included the HIV/AIDS Knowledge Assessment (HIV-KA) and Reactions to Homosexuality Scale (RHS); higher scores indicate greater knowledge and greater internalized homonegativity, respectively. Scales were standardized for analysis. Associations with current PrEP use were estimated using adjusted odds ratios (aOR) with 95% confidence intervals (95%CI).FindingsAmong 2398 PrEP-eligible MSM, n = 370 (15·4%) reported current PrEP use. Increasing HIV-KA scores were associated with greater odds of PrEP use (aOR 1·70 [95%CI 1·41-2·04], p &lt; 0·001), and increasing RHS scores with lower odds of PrEP use (aOR 0·83 [95%CI 0·73-0·96], p = 0·010). PrEP use was lower among 18-24 versus 40+-years-old MSM (aOR 0·43 [95%CI 0·27-0·69], p = 0·005), and in Black versus White/Asian respondents (aOR 0·51 [95%CI 0·31-0·85], p = 0·040).InterpretationAmong PrEP-eligible Brazilian MSM, HIV knowledge was associated with increased PrEP use and internalized homonegativity with decreased use. Wider dissemination of HIV prevention knowledge and addressing stigma experienced by MSM could promote increased PrEP use.FundingNational Institute of Mental Health, Fiocruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico

Awareness of Prevention Strategies and Willingness to Use Preexposure Prophylaxis in Brazilian Men Who Have Sex With Men Using Apps for Sexual Encounters: Online Cross-Sectional Study

Submitted by Fábio Marques ([email protected]) on 2018-09-06T14:18:22Z No. of bitstreams: 1 Awareness of Prevention Strategies and Willingness_Thiago_Torres_INI_Lapclin-AIDS_2018.pdf: 826237 bytes, checksum: e824cc149a67d6dcf486e4d70139339d (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-09-27T15:12:37Z (GMT) No. of bitstreams: 1 Awareness of Prevention Strategies and Willingness_Thiago_Torres_INI_Lapclin-AIDS_2018.pdf: 826237 bytes, checksum: e824cc149a67d6dcf486e4d70139339d (MD5)Made available in DSpace on 2018-09-27T15:12:37Z (GMT). No. of bitstreams: 1 Awareness of Prevention Strategies and Willingness_Thiago_Torres_INI_Lapclin-AIDS_2018.pdf: 826237 bytes, checksum: e824cc149a67d6dcf486e4d70139339d (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilEscola Nacional de Ciências Estatísticas, Rio de Janeiro, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, BrasilGeosocial networking (GSN) smartphone apps are becoming the main venue for sexual encounters among Brazilian men who have sex with men (MSM). To address the increased HIV incidence in this population, preexposure prophylaxis (PrEP) was recently implemented in the Brazilian public health system in the context of combined HIV prevention

Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control

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 < 1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (< 1%); all VCs showed a high number of mutations, with significant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure. Conclusions The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants