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      High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV Infection: the PrEP Brasil demonstration project

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          Abstract

          Introduction: The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW).

          Methods: PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and São Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (<350 fmol/punch, ≥350–699 fmol/punch and ≥700 fmol/punch).

          Results: 1,270 individuals were assessed for participation; n = 738 were potentially eligible and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled individuals were younger, had lower HIV risk perception and had lower PrEP awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP concentrations, 94.1% in the protective range (≥350 fmol/punch, consistent with ≥2 pills per week), and 78% were in the highly protective range (≥700 fmol/punch, ≥4 pills per week). Participants with ≥12 years of schooling had 1.9 times the odds (95%CI 1.10–3.29) of a higher versus lower drug level than participants with <12 years of schooling. Condomless receptive anal intercourse in the prior 3 months was also associated with higher drug levels (adjusted OR = 1.78; 95% CI 1.08–2.94).

          Conclusions: The high uptake and early adherence indicate that PrEP for high-risk MSM and TGW can be successfully delivered in the context of the Brazilian Public Health System. Interventions to address disparities on PrEP awareness and HIV risk perception among the younger and less educated are urgently needed in order to maximize the impact of this prevention strategy on the reduction of HIV infection among MSM and TGW in Brazil.

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          Most cited references26

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          Applied Logistic Regression

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            Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline.

            The aim was to formulate practice guidelines for endocrine treatment of transsexual persons. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person's genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person's desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons.
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              Six Persistent Research Misconceptions

              ABSTRACT Scientific knowledge changes rapidly, but the concepts and methods of the conduct of research change more slowly. To stimulate discussion of outmoded thinking regarding the conduct of research, I list six misconceptions about research that persist long after their flaws have become apparent. The misconceptions are: 1) There is a hierarchy of study designs; randomized trials provide the greatest validity, followed by cohort studies, with case–control studies being least reliable. 2) An essential element for valid generalization is that the study subjects constitute a representative sample of a target population. 3) If a term that denotes the product of two factors in a regression model is not statistically significant, then there is no biologic interaction between those factors. 4) When categorizing a continuous variable, a reasonable scheme for choosing category cut-points is to use percentile-defined boundaries, such as quartiles or quintiles of the distribution. 5) One should always report P values or confidence intervals that have been adjusted for multiple comparisons. 6) Significance testing is useful and important for the interpretation of data. These misconceptions have been perpetuated in journals, classrooms and textbooks. They persist because they represent intellectual shortcuts that avoid more thoughtful approaches to research problems. I hope that calling attention to these misconceptions will spark the debates needed to shelve these outmoded ideas for good.
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                Author and article information

                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                ZIAS
                zias20
                Journal of the International AIDS Society
                Taylor & Francis
                1758-2652
                2017
                6 April 2017
                : 20
                : 1
                : 21472
                Affiliations
                [ a ] FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas , Rio de Janeiro, Brazil
                [ b ] School of Medicine, Universidade de São Paulo , Brazil
                [ c ] School of Medicine, Universidade de São Paulo , São Paulo, Brazil
                [ d ] Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver , Aurora, CO, USA
                [ e ] San Francisco Department of Public Health, Bridge HIV , San Francisco, CA, USA
                Author notes
                [ § ]Corresponding author: Beatriz Grinsztejn, INI/FIOCRUZ , Avenida Brasil 4365, Manguinhos, Rio de Janeiro 21040-360, Brazil. Tel: 55-21-3865-9128. gbeatriz@ 123456ini.fiocruz.br
                [*]

                Contributed equally as last authors

                Clinical Trial Number 01989611

                Author information
                http://orcid.org/0000-0003-3692-5155
                Article
                1309878
                10.7448/IAS.20.1.21472
                5515021
                28418232
                990b7ce5-cac1-4624-bc1c-ae526cdb64d6
                © 2017 Hoagland B et al; licensee International AIDS Society.

                licensee International AIDS Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 September 2016
                : 19 March 2017
                Page count
                Figures: 2, Tables: 3, References: 47, Pages: 15
                Funding
                The study was sponsored by the Brazilian Ministry of Health (#01/2013 BRA/K57), CNPq (#402004/2012-4, # 454931/2014-0) SVS (#281/2013), FAPERJ (#E-26/110.261/2014) and FAPESP (#2012/51743-0). PML and BG acknowledge funding from the National Council of Technological and Scientific Development and the FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. EGK acknowledges funding from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo).Gilead Sciences donated the study drug and covered the costs related to drug level assessment, but had no role in the study design, collection, analysis, and interpretation of data, writing of the manuscript or the decision to submit the manuscript for publication.
                Categories
                Article
                Research Article

                Infectious disease & Microbiology
                pre-exposure prophylaxis,hiv prevention,msm,transgender women,prep uptake,prep adherence,drug levels

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