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      Trends and outcomes of late initiation of combination antiretroviral therapy driven by late presentation among HIV-positive Taiwanese patients in the era of treatment scale-up

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          Abstract

          Objectives

          The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan.

          Methods

          Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm 3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART.

          Results

          We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm 3 in 2012 to 298 cells/mm 3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 ( P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04–1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04–1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33–2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04–2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14–13.65) and older age (AHR, 1.06; 95% CI, 1.03–1.10).

          Conclusions

          While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population.

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          Most cited references18

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          Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

          An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.
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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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              Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

              Introduction Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation. Methods Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm3 or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined. Results A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm3. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm3 in 2008 to a peak of 302 cells/mm3 after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035). Conclusions Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 June 2017
                2017
                : 12
                : 6
                : e0179870
                Affiliations
                [1 ]Department of Medicine, National Taiwan University Hospital Jin-Shan Branch, New Taipei City, Taiwan
                [2 ]Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan
                [3 ]School of Public Health, National Yang-Ming University, Taipei, Taiwan
                [4 ]Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
                [5 ]Department of Medicine, National Cheng Kung University Medical College, Tainan, Taiwan
                [6 ]Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
                [7 ]School of Medicine, National Yang-Ming University, Taipei, Taiwan
                [8 ]Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
                [9 ]School of Medicine, Chung Shan Medical University, Taichung, Taiwan
                [10 ]Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
                [11 ]Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
                [12 ]Department of Health and Nutrition, Chia Nan University of Pharmacy and Sciences, Tainan, Taiwan
                [13 ]Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
                [14 ]Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
                [15 ]Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
                [16 ]Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
                [17 ]Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan
                [18 ]School of Public Health, Taipei Medical University, Taipei, Taiwan
                [19 ]Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                [20 ]Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
                [21 ]Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
                [22 ]China Medical University, Taichung, Taiwan
                Azienda Ospedaliera Universitaria di Perugia, ITALY
                Author notes

                Competing Interests: One of the authors, Hung CC, has the following competing interests: research support from Janssen, Merck, Bristol-Myers Squibb, and ViiV, speaker honoraria from Abbvie, Bristol-Myers Squibb, Gilead Sciences, and ViiV, and serving on advisory boards for Gilead Sciences, Janssen, ViiV, and Abbvie. The other authors have no competing interest to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                • Conceptualization: KYL SHC CCH.

                • Data curation: CYC CWL CJY MST CEL YTL HJT NCW TYL YCL SPL YSH JYZ WCK SHC CCH.

                • Formal analysis: KYL MST SHC CCH.

                • Funding acquisition: CCH.

                • Investigation: CYC CWL CJY MST CEL YTL HJT NCW TYL YCL SPL YSH JYZ WCK SHC CCH.

                • Methodology: KYL SHC CCH.

                • Project administration: KYL SHC CCH.

                • Supervision: SHC CCH.

                • Visualization: KYL SHC CCH.

                • Writing – original draft: KYL SHC CCH.

                • Writing – review & editing: KYL SHC CCH.

                ¶ Membership of the Taiwan HIV Study Group is provided in the Acknowledgments.

                Article
                PONE-D-17-02655
                10.1371/journal.pone.0179870
                5493332
                28665938
                b52a206d-a906-464a-96ef-7c6c5466bd63
                © 2017 Lin 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
                : 20 January 2017
                : 6 June 2017
                Page count
                Figures: 3, Tables: 4, Pages: 14
                Funding
                The authors would like to thank Taiwan Centers for Disease Control for research grant support (grant number MOHW103-CDC-C-114-000405 to C.-C. H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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