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      Predictors of timely linkage‐to‐ART within universal test and treat in the HPTN 071 (PopART) trial in Zambia and South Africa: findings from a nested case‐control study

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          Abstract

          Introduction

          HPTN 071 (PopART) is a three‐arm community randomized trial in Zambia and South Africa evaluating the impact of a combination HIV prevention package, including universal test and treat (UTT), on HIV incidence. This nested study examined factors associated with timely linkage‐to‐care and ART initiation (TLA) (i.e. within six‐months of referral) in the context of UTT within the intervention communities of the HPTN 071 (PopART) trial.

          Methods

          Of the 7572 individuals identified as persons living with HIV (PLWH) (and not on antiretroviral treatment (ART)) during the first year of the PopART intervention provided by Community HIV‐care Providers (CHiPs) through door‐to‐door household visits, individuals who achieved TLA (controls) and those who did not (cases), stratified by gender and community, were randomly selected to be re‐contacted for interview. Standardized questionnaires were administered to explore factors potentially associated with TLA, including demographic and behavioural characteristics, and participants’ opinions on HIV and related services. Odds ratios comparing cases and controls were estimated using a multi‐variable logistic regression.

          Results

          Data from 705 participants (333 cases/372 controls) were analysed. There were negligible differences between cases and controls by demographic characteristics including age, marital or socio‐economic position. Prior familiarity with the CHiPs encouraged TLA (aOR of being a case: 0.58, 95% CI: 0.39 to 0.86, p = 0.006).

          Participants who found clinics overcrowded (aOR: 1.51, 95% CI: 1.08 to 2.12, p = 0.006) or opening hours inconvenient (aOR: 1.63, 95% CI: 1.06 to 2.51, p = 0.02) were less likely to achieve TLA, as were those expressing stronger feelings of shame about having HIV ( p trend = 0.007). Expressing “not feeling ready” (aOR: 2.75, 95% CI: 1.89 to 4.01, p < 0.001) and preferring to wait until they felt sick (aOR: 2.00, 95% CI: 1.27 to 3.14, p = 0.02) were similarly indicative of being a case. Worrying about being seen in the clinic or about how staff treated patients was not associated with TLA.

          While the association was not strong, we found that the greater the number of self‐reported lifetime sexual partners the more likely participants were to achieve TLA ( p trend = 0.06). There was some evidence that participants with HIV‐positive partners on ART were less likely to be cases (aOR: 0.75, 95% CI: 0.53 to 1.06, p = 0.07).

          Discussion

          The lack of socio‐demographic differences between cases and controls is encouraging for a “universal” intervention that seeks to ensure high coverage across whole communities. Making clinics more “patient‐friendly” could enhance treatment uptake further. The finding that those with higher risk behaviour are more actively engaging with UTT holds promise for treatment‐as‐prevention.

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          Most cited references11

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          Stigma: Notes on the management of spoiled identity.

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            Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial

            Background Attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression. Methods and findings We conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. Conclusions Same-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease. Trial registration This study is registered with ClinicalTrials.gov number NCT01900080
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              Trends in CD4 count at presentation to care and treatment initiation in sub-Saharan Africa, 2002-2013: a meta-analysis.

              Both population- and individual-level benefits of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) are contingent on early diagnosis and initiation of therapy. We estimated trends in disease status at presentation to care and at ART initiation in sub-Saharan Africa. We searched PubMed for studies published January 2002-December 2013 that reported CD4 cell count at presentation or ART initiation among adults in sub-Saharan Africa. We abstracted study sample size, year(s), and mean CD4 count. A random-effects meta-regression model was used to obtain pooled estimates during each year of the observation period. We identified 56 articles reporting CD4 count at presentation (N = 295 455) and 71 articles reporting CD4 count at ART initiation (N = 549 702). The mean estimated CD4 count in 2002 was 251 cells/µL at presentation and 152 cells/µL at ART initiation. During 2002-2013, neither CD4 count at presentation (β = 5.8 cells/year; 95% confidence interval [CI], -10.7 to 22.4 cells/year), nor CD4 count at ART initiation (β = -1.1 cells/year; 95% CI, -8.4 to 6.2 cells/year) increased significantly. Excluding studies of opportunistic infections or prevention of mother-to-child transmission did not alter our findings. Among studies conducted in South Africa (N = 14), CD4 count at presentation increased by 39.9 cells/year (95% CI, 9.2-70.2 cells/year; P = .02), but CD4 count at ART initiation did not change. CD4 counts at presentation to care and at ART initiation in sub-Saharan Africa have not increased over the past decade. Barriers to presentation, diagnosis, and linkage to HIV care remain major challenges that require attention to optimize population-level benefits of ART. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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                Author and article information

                Contributors
                kalpana.sabapathy@lshtm.ac.uk
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                18 December 2017
                December 2017
                : 20
                : 4 ( doiID: 10.1002/jia2.2017.20.issue-4 )
                : e25037
                Affiliations
                [ 1 ] London School of Hygiene and Tropical Medicine London United Kingdom
                [ 2 ] Desmond Tutu TB Centre Western Cape South Africa
                [ 3 ] Desmond Tutu TB Centre Department of Paediatrics and Child Health Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa
                [ 4 ] International Centre for Research on Women Washington DC USA
                [ 5 ] Imperial College London London United Kingdom
                Author notes
                [*] [* ] Corresponding author: Kalpana Sabapathy, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. Tel: +44 207 927 2155. ( kalpana.sabapathy@ 123456lshtm.ac.uk )
                Author information
                http://orcid.org/0000-0001-8017-6716
                http://orcid.org/0000-0003-1676-7583
                Article
                JIA225037
                10.1002/jia2.25037
                5810326
                29251433
                9bebccc0-3d39-4bd2-8330-79499f23b3b3
                © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 June 2017
                : 27 November 2017
                Page count
                Figures: 2, Tables: 3, Pages: 11, Words: 9911
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases
                Award ID: UM1‐AI068619
                Award ID: UM1‐AI068617
                Award ID: UM1‐AI068613
                Funded by: U.S. President's Emergency Plan for AIDS Relief
                Funded by: International Initiative for Impact Evaluation
                Funded by: Bill & Melinda Gates Foundation
                Funded by: National Institute on Drug Abuse
                Funded by: National Institute of Mental Health
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                jia225037
                December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:13.02.2018

                Infectious disease & Microbiology
                linkage to care,art initiation,cascade of care,differentiated care,universal test and treat,universal treatment,immediate art,treatment as prevention

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