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      Sexually transmitted infections and HIV in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy

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          Abstract

          Introduction

          HIV is a unique sexually transmitted infection ( STI) that is greatly affected by other concomitant “classical” bacterial and viral STIs that cause genital ulcers and/or mucosal inflammation. STIs also serve as a marker for risky sexual behaviours. STIs increase infectiousness of people living with HIV by increasing the viral concentration in the genital tract, and by increasing the potential for HIV acquisition in people at risk for HIV. In addition, some STIs can increase blood HIV concentration and promote progression of disease. This review is designed to investigate the complex relationship between HIV and classical STIs.

          Discussion

          Treatment of STIs with appropriate antibiotics reduces HIV in blood, semen and female genital secretions. However, community‐based trials could not reliably reduce the spread of HIV by mass treatment of STIs. Introduction of antiretroviral agents for the treatment and prevention of HIV has led to renewed interest in the complex relationship between STIs and HIV. Antiretroviral treatment ( ART) reduces the infectiousness of HIV and virtually eliminates the transmission of HIV in spite of concomitant or acquired STIs. However, while ART interrupts HIV transmission, it does not stop intermittent shedding of HIV in genital secretions. Such shedding of HIV is increased by STIs, although the viral copies are not likely replication competent or infectious. Pre‐exposure prophylaxis (Pr EP) of HIV with the combination of tenofovir disoproxil fumarate and emtricitabine ( TDF/ FTC) prevents HIV acquisition in spite of concomitant STIs.

          Conclusions

          STIs remain pandemic, and the availability of ART may have led to an increase in STIs, as fear of HIV has diminished. Classical STIs present a huge worldwide health burden that cannot be separated from HIV, and they deserve far more attention than they currently receive.

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          Most cited references89

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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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            Sexually transmitted infections: challenges ahead.

            WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.
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              The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

              Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1–specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell–mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell–driven escape.

                Author and article information

                Contributors
                mscohen@med.unc.edu
                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
                30 August 2019
                August 2019
                : 22
                : Suppl Suppl 6 , Understanding and addressing the HIV and STI syndemics. Guest Editor: Kenneth H Mayer, Henry JC de Vries ( doiID: 10.1002/jia2.v22.s6 )
                : e25355
                Affiliations
                [ 1 ] UNC School of Medicine Institute for Global Health & Infectious Diseases Chapel Hill NC USA
                [ 2 ] Department of Microbiology and Immunology UNC Chapel Hill NC USA
                [ 3 ] Department of Epidemiology Gillings School of Global Public Health UNC Chapel Hill NC USA
                Author notes
                [*] [* ] Corresponding Author: Myron S Cohen, 130 Mason Farm Road, CB# 7030, Bioinformatics Building, Suite 2115, Chapel Hill, NC 27599‐7030. Tel: 919‐962‐4646. ( mscohen@ 123456med.unc.edu )
                Article
                JIA225355
                10.1002/jia2.25355
                6715951
                31468737
                f41f5dbd-766c-4eab-910c-fae890929b00
                © 2019 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 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
                : 26 January 2019
                : 26 June 2019
                Page count
                Figures: 0, Tables: 0, Pages: 9, Words: 9912
                Funding
                Funded by: HIV Prevention Trials Network
                Award ID: U01‐AI068619
                Funded by: UNC Center for AIDS Research
                Award ID: CFAR P30‐AI50410
                Funded by: NIDDK
                Award ID: R37‐DK049381
                Funded by: NIH/NIAID
                Award ID: T32‐AI070114
                Award ID: T32‐AI007001
                Categories
                Review
                Review
                Custom metadata
                2.0
                jia225355
                August 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.8 mode:remove_FC converted:30.08.2019

                Infectious disease & Microbiology
                sti,std,hiv,art,prep,shedding,acquisition,transmission
                Infectious disease & Microbiology
                sti, std, hiv, art, prep, shedding, acquisition, transmission

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