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      The importance of the “how”: the case for differentiated service delivery of long‐acting and extended delivery regimens for HIV prevention and treatment

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          Abstract

          Introduction

          Long‐acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access.

          Discussion

          The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment—the vast majority on a daily fixed‐dose combination oral pill that is largely available, affordable and well‐tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre‐exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self‐management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re‐initiation.

          Conclusions

          To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical.

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          Most cited references42

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          Outcomes for Implementation Research: Conceptual Distinctions, Measurement Challenges, and Research Agenda

          An unresolved issue in the field of implementation research is how to conceptualize and evaluate successful implementation. This paper advances the concept of “implementation outcomes” distinct from service system and clinical treatment outcomes. This paper proposes a heuristic, working “taxonomy” of eight conceptually distinct implementation outcomes—acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability—along with their nominal definitions. We propose a two-pronged agenda for research on implementation outcomes. Conceptualizing and measuring implementation outcomes will advance understanding of implementation processes, enhance efficiency in implementation research, and pave the way for studies of the comparative effectiveness of implementation strategies.
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            Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

            Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).
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              Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women

              New England Journal of Medicine, 367(5), 399-410
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                Author and article information

                Contributors
                anna.grimsrud@iasociety.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
                13 July 2023
                July 2023
                : 26
                : Suppl 2 ( doiID: 10.1002/jia2.v26.S2 )
                : e26095
                Affiliations
                [ 1 ] HIV Programmes and Advocacy IAS – the International AIDS Society Cape Town South Africa
                [ 2 ] Centre for Infectious Disease Epidemiology and Research University of Cape Town Cape Town South Africa
                [ 3 ] Wits RHI University of the Witwatersrand Johannesburg South Africa
                [ 4 ] Global Health Bill & Melinda Gates Foundation Seattle Washington USA
                [ 5 ] Primary Health Care PATH Seattle Washington USA
                [ 6 ] Primary Health Care PATH Hanoi Vietnam
                [ 7 ] Lean on Me Foundation Nairobi Kenya
                [ 8 ] School of Public Health Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya
                [ 9 ] Department of Global Health University of Washington Seattle Washington USA
                [ 10 ] National Empowerment Network of People Living with HIV/AIDS in Kenya (NEPHAK) Nairobi Kenya
                [ 11 ] The Thai Red Cross AIDS Research Centre – PREVENTION Bangkok Thailand
                [ 12 ] Global Network of People Living with HIV (GNP+) Cape Town South Africa
                [ 13 ] Global HIV, Hepatitis, and Sexually Transmitted Infections Programmes World Health Organization Geneva Switzerland
                [ 14 ] IAS ‐ International AIDS Society Geneva Switzerland
                Author notes
                [*] [* ] Corresponding author: Anna Grimsrud, 3 Doris Road, Claremont 7708, South Africa. Tel: +27 78 129 7304. ( anna.grimsrud@ 123456iasociety.org )

                Author information
                https://orcid.org/0000-0002-1199-8377
                https://orcid.org/0000-0003-0376-1019
                https://orcid.org/0000-0003-2028-4779
                https://orcid.org/0000-0002-8062-0933
                https://orcid.org/0000-0002-0036-3165
                Article
                JIA226095
                10.1002/jia2.26095
                10339003
                37439076
                f58c7681-0e26-4a2d-9206-a6411d59a695
                © 2023 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
                : 08 November 2022
                : 27 April 2023
                Page count
                Figures: 0, Tables: 1, Pages: 7, Words: 5783
                Funding
                Funded by: Bill & Melinda Gates Foundation , doi 10.13039/100000865;
                Award ID: INV002610
                Award ID: INV0047567
                Categories
                Commentary
                Commentary
                Custom metadata
                2.0
                July 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.1 mode:remove_FC converted:13.07.2023

                Infectious disease & Microbiology
                differentiated service delivery,long‐acting extended delivery,hiv prevention,hiv treatment,arv,health systems

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