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      Correlates of self-reported and biomarker based adherence to daily oral HIV pre-exposure prophylaxis among a cohort of predominantly men who have sex with men in Nigeria

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          Abstract

          Introduction

          HIV pre-exposure prophylaxis (PrEP) significantly reduces the risk of HIV acquisition. However, studies have demonstrated discordance between self-reported measures and biomedical benchmarks of PrEP adherence. We estimated the correlation between self-reported PrEP adherence and PrEP biomarkers and explored factors associated with adherence among men who have sex with men (MSM) in Nigeria.

          Methods

          TRUST-PrEP, an open-label, prospective study; conducted in Abuja between April 2018 and May 2019. MSM ≥ 18 years with substantial HIV risk were enrolled. Participants reported PrEP adherence in the last month using a 4-point scale from “poor” to “perfect” and serum samples for PrEP biomarkers were collected at months 3 and 9. Serum tenofovir concentration was measured by liquid chromatography-tandem mass spectrometry and considered protective for adherence if ≥ 4.2 ng/ml. Spearman’s rank correlation was used to estimate correlation between self-reported adherence and measured tenofovir levels. Generalized estimating equations with a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between self-reported adherence and laboratory-measured adherence.

          Results

          A total of 219 MSM with median age 23 (interquartile range 20–27) years had at least one PrEP biomarker assay. Only 66/219 (30%) had at least one record of protective tenofovir concentration. Correlation between tenofovir and self-reported adherence at 3 and 9 months were 0.1 and 0.02 respectively. Furthermore, 17/219 (8%,) and 49/219 (22%) had serum tenofovir of 4.2–35.4 ng/mL and ≥ 35.5 ng/mL, corresponding to at least 4 and 7 days’ PrEP use in a week, respectively. PrEP adherence was higher among participants introduced to PrEP in the clinics compared with communities (aOR: 8.35, 95%CI: [3.24, 21.5]) and those with same-sex practices family disclosure (aOR: 3.60 95% CI: [1.73, 7.51]).

          Conclusion

          Self-reported PrEP adherence poorly correlated with biomarkers. Facilitating clinic-based PrEP introduction and disclosure of same-sex practices to family among MSM may improve PrEP adherence.

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          Most cited references56

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          Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

          Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).
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            Estimation of the Youden Index and its associated cutoff point.

            The Youden Index is a frequently used summary measure of the ROC (Receiver Operating Characteristic) curve. It both, measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value (cutoff point) for the marker. In this paper we compare several estimation procedures for the Youden Index and its associated cutoff point. These are based on (1) normal assumptions; (2) transformations to normality; (3) the empirical distribution function; (4) kernel smoothing. These are compared in terms of bias and root mean square error in a large variety of scenarios by means of an extensive simulation study. We find that the empirical method which is the most commonly used has the overall worst performance. In the estimation of the Youden Index the kernel is generally the best unless the data can be well transformed to achieve normality whereas in estimation of the optimal threshold value results are more variable.
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              Global epidemiology of HIV infection in men who have sex with men.

              Epidemics of HIV in men who have sex with men (MSM) continue to expand in most countries. We sought to understand the epidemiological drivers of the global epidemic in MSM and why it continues unabated. We did a comprehensive review of available data for HIV prevalence, incidence, risk factors, and the molecular epidemiology of HIV in MSM from 2007 to 2011, and modelled the dynamics of HIV transmission with an agent-based simulation. Our findings show that the high probability of transmission per act through receptive anal intercourse has a central role in explaining the disproportionate disease burden in MSM. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiological data show substantial clustering of HIV infections in MSM networks, and higher rates of dual-variant and multiple-variant HIV infection in MSM than in heterosexual people in the same populations. Prevention strategies that lower biological transmission and acquisition risks, such as approaches based on antiretrovirals, offer promise for controlling the expanding epidemic in MSM, but their potential effectiveness is limited by structural factors that contribute to low health-seeking behaviours in populations of MSM in many parts of the world. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: MethodologyRole: ValidationRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Funding acquisitionRole: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 March 2023
                2023
                : 18
                : 3
                : e0282999
                Affiliations
                [1 ] Department of Public Health and Epidemiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
                [2 ] International Research Center of Excellence, Institute of Human Virology, Abuja, Nigeria
                [3 ] Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
                [4 ] Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
                [5 ] School of Social Work, University of Maryland, Baltimore, MD, United States of America
                [6 ] Division of Biostatistics and Bioinformatics, Department of Public Health and Epidemiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
                [7 ] Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America
                [8 ] U.S Military HIV Research Program, Silver Spring, Maryland, United States of America
                [9 ] The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
                [10 ] Center for International Health, Education, and Biosecurity, Abuja, Nigeria
                UNSW Australia, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ¶ Membership of the TRUST/RV368 Study Group is listed in the Acknowledgments.

                Author information
                https://orcid.org/0000-0002-2051-002X
                https://orcid.org/0000-0001-5395-6071
                https://orcid.org/0000-0001-5947-265X
                Article
                PONE-D-22-04938
                10.1371/journal.pone.0282999
                10019705
                36928630
                177dea01-edf9-44c8-bbef-8e5b714fd3a2
                © 2023 Adeyemi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 February 2022
                : 28 February 2023
                Page count
                Figures: 6, Tables: 3, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: D43TW010051
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 MH099001
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 MH110358
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: W81XWH-11-2-0174
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: W81XWH-18-2-0040
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000030, Centers for Disease Control and Prevention;
                Award ID: NU2GGH002099
                Award Recipient :
                Grant 1 Recipient: MEC Grant number: D43TW010051 and R01 MH099001 Funding source: National Institutes of Health. URL: https://www.nih.gov/ Grant 2 Recipient: SB Grant number: R01 MH110358 Funding source: National Institutes of Health. URL: https://www.nih.gov/ Other Grants: In addition, this work was supported by cooperative agreements between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (Grant number: W81XWH-11-2-0174 and W81XWH-18-2-0040 URL: https://www.defense.gov/) as well as by the President’s Emergency Plan for AIDS Relief through a cooperative agreement between the Department of Health and Human Services/Centers for Disease Control and Prevention, Global AIDS Program, and the Institute for Human Virology-Nigeria. Grant number: NU2GGH002099 https://www.cdc.gov/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Custom metadata
                Data cannot be shared publicly due to the extreme stigmatization of our study participants and the risk of prosecution if they are linked with de-identified data. The study investigators are committed to ensuring the safety of every participant and protecting their privacy, especially in a same-sex practise rights-constrained setting like our study's. The approved IRB protocol however permits the publication of aggregated data and this will be available on request from the the email address below: implementationscienceunit@ 123456SOMUMaryland.onmicrosoft.com .

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