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      Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review

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          Abstract

          Objectives

          As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation.

          Design

          Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa.

          Data sources

          PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences.

          Eligibility criteria

          Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure.

          Data extraction and synthesis

          We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature.

          Results

          Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret.

          Conclusions

          The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%–50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure.

          PROSPERO registration number

          CRD42022324136.

          Related collections

          Most cited references29

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy

            Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV preexposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled intracellular tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) to assess adherence and corresponding PrEP outcomes. We conducted a prospective, randomized, crossover pharmacokinetic study of TFV-DP in DBS during 33%, 67%, or 100% of daily dosing under directly observed therapy (DOT). Participants were assigned to two 12-week dosing regimens, separated by a 12-week washout. Forty-eight adults (25 women) from Denver and San Francisco were included. TFV-DP exhibited a median half-life of 17 days, reaching steady state in 8 weeks. TFV-DP was dose proportional with mean (SD) steady-state concentrations of 530 (159), 997 (267), and 1,605 (405) fmol/punch for the 33%, 67%, and 100% arms, respectively. Prior work in MSM demonstrated clinically meaningful TFV-DP thresholds of 350, 700, and 1,250 fmol/punch, which were estimated 25th percentiles for 2, 4, and 7 doses/week. In the present study, corresponding TFV-DP was within 3% of the prior estimates, and subgroups by site, race, and sex were within 14% of prior estimates, although males had 17.6% (95% confidence intervals [CIs], 6.5, 27.4%) lower TFV-DP than females. The thresholds of 350, 700, and 1,250 fmol/punch were achieved by 75% of men taking ≥1.2, 3.2, and 6 doses/week and 75% of women taking ≥0.6, 2.0, and 5.3 doses/week, indicating that lower dosing reached these thresholds for both sexes. In conclusion, TFV-DP arising from DOT was similar to previous estimates and is useful for interpreting PrEP adherence and study outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02022657.)
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              Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008-2013.

              We previously published systematic reviews of retention in care after antiretroviral therapy initiation among general adult populations in sub-Saharan Africa. We estimated 36-month retention at 73% for publications from 2007 to 2010. This report extends the review to cover 2008-2013 and expands it to all low- and middle-income countries.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2023
                19 November 2023
                : 13
                : 11
                : e071283
                Affiliations
                [1 ]departmentDepartment of Global Health , Ringgold_27118Boston University School of Public Health , Boston, Massachusetts, USA
                [2 ]departmentHealth Economics and Epidemiology Research Office , Ringgold_37708University of the Witwatersrand Faculty of Health Sciences , Johannesburg, Gauteng, South Africa
                [3 ]departmentAlumni Medical Library , Ringgold_12259Boston University School of Medicine , Boston, Massachusetts, USA
                Author notes
                [Correspondence to ] Dr Sydney Rosen; sbrosen@ 123456bu.edu
                Author information
                http://orcid.org/0000-0002-6560-2964
                Article
                bmjopen-2022-071283
                10.1136/bmjopen-2022-071283
                10660894
                37984944
                dfa5e989-b66c-42f8-9aa8-6de7cc07965f
                © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 20 December 2022
                : 13 September 2023
                Funding
                Funded by: Bill & Melinda Gates Foundation;
                Award ID: INV-031690
                Categories
                HIV/AIDS
                1506
                Original research
                Custom metadata
                unlocked

                Medicine
                epidemiology,hiv & aids,public health,health services accessibility
                Medicine
                epidemiology, hiv & aids, public health, health services accessibility

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