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      Quantifying the impact of cascade inequalities: a modelling study on the prevention impacts of antiretroviral therapy scale-up in Eswatini

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          Abstract

          Background

          Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95–95-95 targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate additional HIV infections expected in Eswatini if cascade scale-up had not been equal, and under which epidemic conditions these inequalities could have the largest influence.

          Methods

          Drawing on population-level and FSW-specific surveys in Eswatini, we developed a compartmental model of heterosexual HIV transmission which included eight subpopulations and four sexual partnership types. We calibrated the model to stratified HIV prevalence, incidence, and ART cascade data. Taking observed cascade scale-up in Eswatini as the base-case — reaching 95–95-95 in the overall population by 2020 — we defined four counterfactual scenarios in which the population overall reached 80–80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60–40-80. We quantified relative additional cumulative HIV infections by 2030 in counterfactual vs base-case scenarios. We further estimated linear effects of viral suppression gap among FSW and clients on additional infections by 2030, plus effect modification by FSW/client population sizes, rates of turnover, and HIV prevalence ratios.

          Findings

          Compared with the base-case scenario, leaving behind neither FSW and nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 13.3 (9.2, 18.7) % vs 26.7 (19.7, 33.8) % if both were left behind — a 104 (50, 167) % increase. The effect of lower cascade on additional infections was larger for clients vs FSW, and client population size, turnover, and prevalence ratios were the largest modifiers of both effects.

          Interpretation

          Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade, particularly those that intersect with high transmission risk, could maximize incidence reductions from cascade scale-up.

          Funding

          Natural Sciences and Engineering Research Council of Canada; Ontario Ministry of Colleges and Universities; Canadian Institutes of Health Research; National Institute of Allergy and Infectious Diseases.

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          Most cited references37

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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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            Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

            New England Journal of Medicine, 373(9), 795-807
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              Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis.

              High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per microL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161-265) cells per microL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0.37 (95% CI 0.09-2.04) per 100 person-years in those who had initiated treatment and 2.24 (1.84-2.72) per 100 person-years in those who had not-a 92% reduction (adjusted incidence rate ratio 0.08, 95% CI 0.00-0.57, p=0.004). In participants not on ART, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per microL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission. Bill & Melinda Gates Foundation; US National Institutes of Health. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                medRxiv
                MEDRXIV
                medRxiv
                Cold Spring Harbor Laboratory
                18 February 2024
                : 2024.02.16.24302584
                Affiliations
                [1 ]MAP Centre for Urban Health Solutions, Unity Health Toronto
                [2 ]Institute of Medical Science, University of Toronto
                [3 ]EpiC, FHI 360, Eswatini
                [4 ]Voice of Our Voices, Eswatini
                [5 ]Bloomberg School of Public Health, Johns Hopkins University
                [6 ]Ministry of Health, Eswatini
                [7 ]Division of Infectious Diseases, Department of Medicine, University of Toronto
                [8 ]Dalla Lana School of Public Health, University of Toronto
                [9 ]Institute for Clinical Evaluative Sciences, Toronto, Ontario
                Author notes
                Author information
                http://orcid.org/0000-0002-0455-5455
                http://orcid.org/0000-0001-8492-5470
                Article
                10.1101/2024.02.16.24302584
                10889039
                38405846
                59a203aa-f98e-46eb-9c7b-8ca2cb576a22

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

                History
                Funding
                Funded by: Natural Sciences and Engineering Research Council of Canada, Ontario Ministry of Colleges and Universities, Canadian Institutes of Health Research
                Award ID: FN-13455
                Funded by: National Institute of Allergy and Infectious Diseases
                Award ID: R01AI170249
                Categories
                Article

                hiv,mathematical model,antiretroviral therapy,sex work,healthcare disparities

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