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      Anti‐retroviral therapy scale‐up and its impact on sex‐stratified tuberculosis notification trends in Uganda

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          Abstract

          Introduction

          In order to end the tuberculosis ( TB) epidemic by 2035, countries must achieve a 10% annual decline in tuberculosis incidence rates by 2025. Provision of antiretroviral therapy ( ART) has been associated with population level decreases in TB notification rates. We aimed to assess whether the progressive scale‐up of ART provision over the past nine years has had an effect on population level trends of TB notification in Uganda stratified by sex and HIV status.

          Methods

          The study area consisted of Kampala and eight surrounding districts. Annual TB notifications and mid‐year populations were used to calculate notification rates per 100,000 population from the study area. Numbers alive and retained on ART were used to calculate ART coverage, overall and by sex. TB notification rates ( TBNRs) overall and stratified by sex and HIV status were calculated for the period 2009 to 2017. Trends in TBNRs before and after rollout of universal ART for pregnant women in 2013 were examined using Poisson regression models. To gain insight into the trends in CD4+ T‐cell counts at ART initiation over the study period, we performed a sub analysis of patient level data from the Infectious Diseases Institute clinic.

          Results

          From 2009 to 2017, ART coverage increased by 27.6% among men and by 35.4% among women. TBNRs declined during the same period. Overall, the average annual percentage decline in TBNRs was −3.5% (95% CI −3.7% to −3.3%), (−2.3% (95% CI −2.6% to −1.9%) in men and −5.4% (95% CI −5.7% to −5.0%) in women). ART coverage increased after 2013 but this was not associated with an accelerated decline in overall TBNRs among HIV‐positive persons −3.6% before 2013 and −5.2% after 2013; p = 0.33. The proportion of patients initiating ART with CD4+ T‐cell count ≤ 200 cells/ mL did not decrease significantly after 2013 (42.2% to 32.2% , p = 0.05).

          Conclusions

          Although ART scale‐up was temporally associated with a decline in TB notification rates, the achieved rates of decline are below those required to achieve the End TB Targets. Additional investments in tuberculosis control should include efforts to promote earlier care seeking and ART initiation among HIV‐positive persons.

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          Most cited references17

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          A Wilcoxon-type test for trend.

          J Cuzick (1985)
          An extension of the Wilcoxon rank-sum test is developed to handle the situation in which a variable is measured for individuals in three or more (ordered) groups and a non-parametric test for trend across these groups is desired. The uses of the test are illustrated by two examples from cancer research.
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            Tuberculosis Incidence Rates during 8 Years of Follow-Up of an Antiretroviral Treatment Cohort in South Africa: Comparison with Rates in the Community

            Background Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community. Methodology/Principal Findings Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4–5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8–14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64–8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0–100, 101–200, 201–300, 301–400, 401–500, 501–700 and ≥700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6–30.3), 11.2 (9.4–13.5), 7.9 (6.4–9.7), 5.0 (3.9–6.6), 5.1 (3.8–6.8), 4.1 (3.1–5.4) and 2.7 (1.7–4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9–78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58–0.65). Conclusions/Significance TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL.
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              Biological differences between the sexes and susceptibility to tuberculosis.

              Globally, far more men than women have tuberculosis. Although the cause of this bias is uncertain, epidemiological factors have historically been considered the driving force. Here, we discuss evidence that biological differences between the sexes may also be important and can affect susceptibility to mycobacterial infection. We discuss the possible underlying mechanisms, with particular focus on how sex hormones modulate the immune responses necessary for resistance to tuberculosis. Studying these differences may provide valuable insight into the components that constitute an effective immune response to this deadly pathogen. © 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
                szawedde@idi.co.ug
                s.hermans@aighd.org
                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
                16 September 2019
                September 2019
                : 22
                : 9 ( doiID: 10.1002/jia2.v22.9 )
                : e25394
                Affiliations
                [ 1 ] The Infectious Diseases Institute College of Health Sciences Makerere University Kampala Uganda
                [ 2 ] Division of Infectious Diseases Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA
                [ 3 ] Ministry of Health National Tuberculosis and Leprosy Program Kampala Uganda
                [ 4 ] Departments of Global Health and Medicine University of Washington Seattle WA USA
                [ 5 ] Department of Global Health Amsterdam Institute for Global Health and Development Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
                Author notes
                [*] [* ] Corresponding Authors: Stella Zawedde‐Muyanja, The Infectious Diseases Institute, College of Health Sciences, Makerere University, P.O. Box 22418, Kampala, Uganda. Tel: +256772591554. ( szawedde@ 123456idi.co.ug ) and Sabine Hermans, Amsterdam UMC, University of Amsterdam, Department of Global Health and Medicine, Amsterdam Institute of Global Health and Development, Amsterdam, the Netherlands. Tel: +31202103960. ( s.hermans@ 123456aighd.org )
                Author information
                https://orcid.org/0000-0002-8823-7082
                https://orcid.org/0000-0001-5677-939X
                Article
                JIA225394
                10.1002/jia2.25394
                6747005
                31529618
                aad5af8d-3222-4a03-8081-32681ed07952
                © 2019 Infectious Diseases Institute. 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 http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 January 2019
                : 06 August 2019
                Page count
                Figures: 4, Tables: 3, Pages: 9, Words: 6531
                Funding
                Funded by: Fogarty International Center
                Funded by: National Institutes for Health
                Award ID: D43TW009771
                Award ID: K01AI138620
                Funded by: TB/HIV Research Excellence
                Funded by: DELTAS Africa Initiative
                Award ID: DEL‐15‐006
                Funded by: Wellcome Trust
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                jia225394
                September 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:17.09.2019

                Infectious disease & Microbiology
                antiretroviral therapy,tuberculosis,sex,policy,notification trends,uganda

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