<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="letter" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">Gates Open Res</journal-id>
            <journal-title-group>
                <journal-title>Gates Open Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2572-4754</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/gatesopenres.16067.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Open Letter</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>An Open Letter on Advancing HIV prevention: Augmenting an ecosystem-based approach to understand prevention decision-making</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 2 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Gantayat</surname>
                        <given-names>Nishan</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-3258-6643</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Baer</surname>
                        <given-names>James</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Gangaramany</surname>
                        <given-names>Alok</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-3908-8463</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Pierce-Messick</surname>
                        <given-names>Rosemary</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Final Mile Consulting, New York, New York, 10007, USA</aff>
                <aff id="a2">
                    <label>2</label>Independent Consultant, London, UK</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:nishan9015@gmail.com">nishan9015@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>2</day>
                <month>8</month>
                <year>2024</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2024</year>
            </pub-date>
            <volume>8</volume>
            <elocation-id>73</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>19</day>
                    <month>7</month>
                    <year>2024</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Gantayat N et al.</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://gatesopenresearch.org/articles/8-73/pdf"/>
            <abstract>
                <p>In the last two decades, HIV programs have been able to avert millions of AIDS-related deaths and reduce HIV incidence. However, the 1.3 million new HIV infections in 2022 remain significantly above the UNAIDS target of fewer than 370,000 new infections by 2025. HIV programs worldwide also did not achieve the UN&#x2019;s 90-90-90 target for testing and treatment set for 2020. Within this broader picture, HIV continues to disproportionately affect key and at-risk populations, including gay men and other men who have sex with men, female sex workers, and adolescent girls and young women. As HIV incidence declines and biomedical advances continue, it will become critical for public-health practitioners to reach key and at-risk populations with prevention services and limit primary transmission.</p>
                <p>In this Open Letter, we focus on demand for HIV prevention to illuminate factors that influence uptake of HIV prevention products and services. These factors exist at three levels of the decision-making ecosystem &#x2013; the individual level, interaction level and systemic level. We argue that approaching HIV prevention solely through the lens of these levels creates a static view of prevention decision-making. There is a need instead for a dynamic viewpoint that can mirror the changing contexts in which users find themselves and make prevention decisions. We demonstrate that the current ecosystem viewpoint is useful to understand the gaps that exist in program implementation, but does not provide adequate insights into the underlying behaviors that contribute to these gaps. To address this, we suggest an approach to include dynamic aspects of decision-making with factors that influence the individual&#x2019;s assessment of risk, their evaluation of the opportunities to use HIV prevention, and their effective use of prevention products.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>HIV Prevention</kwd>
                <kwd>Public Health</kwd>
                <kwd>HIV/AIDS</kwd>
                <kwd>Ecosystem</kwd>
                <kwd>Decision-making</kwd>
                <kwd>Behavioral Science</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>Gates Foundation</funding-source>
                    <award-id>INV-057002</award-id>
                </award-group>
                <funding-statement>This work was supported by the Gates Foundation [INV-057002].</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec sec-type="intro">
            <title>Introduction</title>
            <p>There were around 1.3 million new cases of HIV infection in 2022, marking a 59% decline from the peak of new infections in 1995
                <sup>
                    <xref ref-type="bibr" rid="ref-1">1</xref>
                </sup>. Five countries have already achieved the United Nations 95-95-95 targets set for 2025 (95% of those who are infected with HIV are diagnosed, 95% of those diagnosed are on ART, and 95% of those on ART have untransmissible levels of HIV), which are integral to the UNAIDS strategy to eliminate HIV as a public health threat by 2030
                <sup>
                    <xref ref-type="bibr" rid="ref-2">2</xref>
                </sup>. Among those infected with HIV, approximately 20.8 million AIDS-related deaths have been averted between 1996 and 2022 due to antiretroviral therapy (ART)
                <sup>
                    <xref ref-type="bibr" rid="ref-3">3</xref>
                </sup>.</p>
            <p>The success of HIV programs over the years underscores the importance of strong commitments to public health, including evidence-based policymaking, scaling up of services for those living with HIV, and an increased focus on prevention programs. Advances in biomedical products now present individuals with a range of HIV prevention choices, and the introduction of the dapivirine vaginal ring for women and LA-CAB (long-acting injectable ART) is expected to greatly support the effort to reduce HIV infections
                <sup>
                    <xref ref-type="bibr" rid="ref-4">4</xref>
                </sup>.</p>
            <p>However, the 1.3 million annual new HIV infections remain significantly above the UNAIDS target of fewer than 370,000 new infections by 2025
                <sup>
                    <xref ref-type="bibr" rid="ref-5">5</xref>
                </sup>. Overall, HIV programs worldwide also did not achieve the UN&#x2019;s 90-90-90 target of testing and treatment set for 2020
                <sup>
                    <xref ref-type="bibr" rid="ref-6">6</xref>
                </sup>. Even though new infections have dropped by more than 40% among adolescent girls and boys, adolescent girls and young women remain an at-risk population, with 4,000 acquiring HIV every week
                <sup>
                    <xref ref-type="bibr" rid="ref-1">1</xref>
                </sup>. Yet in sub-Saharan Africa, only 42% of districts with very high HIV incidence have dedicated prevention programs for adolescent girls and young women
                <sup>
                    <xref ref-type="bibr" rid="ref-1">1</xref>
                </sup>.</p>
            <p>The inequities are amplified for key populations, including sex workers, men who have sex with men, transgender people, and people who inject drugs. In a gap analysis for combination prevention in the period 2016&#x2013;2020, sex workers and men who have sex with men showed significant gaps against targets for condom use at last high-risk sex, for HIV prevention program coverage, and for sexually transmitted infection (STI) screening in the last 3 months
                <sup>
                    <xref ref-type="bibr" rid="ref-7">7</xref>
                </sup>. In addition, laws that criminalize people from key populations or their behaviors remain on statute books across much of the world. In 168 countries, some aspect of sex work is criminalized; 67 countries criminalize consensual same-sex intercourse; 20 countries criminalize transgender people; and 143 countries criminalize or otherwise prosecute HIV exposure, non-disclosure, or transmission
                <sup>
                    <xref ref-type="bibr" rid="ref-3">3</xref>
                </sup>.</p>
            <p>With limited access to or scarcity of HIV and other health services, and legal and social discrimination, the HIV pandemic continues to disproportionately impact key populations. In 2022, HIV prevalence was 11 times higher among gay men and other men who have sex with men, four times higher among sex workers, seven times higher among people who inject drugs, and 14 times higher among transgender people, compared with individuals from the general population
                <sup>
                    <xref ref-type="bibr" rid="ref-3">3</xref>
                </sup>. The overall success of reaching HIV prevention targets is therefore dependent on effective uptake of prevention products by key and at-risk populations.</p>
            <p>Different from HIV treatment, HIV prevention comprises an array of interventions with varying frequency of use, and which are adopted in the absence of any immediate health challenges. This presents program planners, policymakers, and funding bodies with the challenge of driving effective prevention programs aligned with the user journey.</p>
            <p>In this Open Letter, we use an ecosystem lens to illuminate factors that influence uptake of HIV prevention products and services. We consider three levels of the decision-making ecosystem. The individual level includes cognitive-psychological-behavioral factors such as relevance, risk saliency, coping ability, and control. The interaction level refers to the individual&#x2019;s interactions with people and programs when engaging with HIV prevention services. Finally, the systemic level refers to structural factors that shape the individual&#x2019;s ecosystem: these include culture, political institutions, programs, and policies. These factors may be barriers or enablers to the individual&#x2019;s decision to use HIV prevention products. We consider the three levels with a focus on the HIV prevention landscape in southern and eastern Africa as it affects three key and at-risk populations: men who have sex with men, female sex workers, and adolescent girls and young women.</p>
            <p>We further discuss that there is scope for augmentation of the current ecosystem approach to include the dynamic aspect of decision-making that usually accompanies uptake of HIV prevention products and services. We believe that HIV prevention will benefit from a more dynamic understanding of the factors that influence the individual&#x2019;s assessment of risk, their evaluation of the opportunities to use HIV prevention, and their effective use of prevention products. Uptake of HIV prevention products and services should not be seen as a single behavior occurring at one time, but as the culmination of multiple behaviors and factors that often exist concurrently.</p>
        </sec>
        <sec>
            <title>Individual level</title>
            <p>An individual&#x2019;s actions related to HIV prevention are strongly influenced by their emotions, which influence the decisions they make, how they make them, and how they perceive and internalize the prevailing risks. This emotional process, explained further below and summarized in 
                <xref ref-type="table" rid="T1">Table 1</xref>, includes aspects such as the relevance of HIV to them, their perception of risk, their ability to cope with the internalized risk, and control over their actions.  
                <xref ref-type="table" rid="T1">Table 1</xref> below summarizes the factors followed by a more detailed explanation.</p>
            <table-wrap id="T1" orientation="portrait" position="anchor">
                <label>Table 1. </label>
                <caption>
                    <title>Summary table for individual level of the user ecosystem.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="2" rowspan="1" valign="top">Individual level is centered on the end-user and includes the cognitive-psychological-behavioral factors affecting their HIV prevention decisions.</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Relevance</bold> 
                                <italic toggle="yes">includes evaluation of importance of HIV prevention for a user</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Relevance for HIV prevention is often seen to be low as users such as adolescent girls and young women and men who have sex with men place higher priorities on economic benefits, safety and relationship stability as compared to HIV prevention.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Risk saliency</bold> 
                                <italic toggle="yes">includes user&#x2019;s attention towards immediate risks associated with HIV</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Risk saliency is affected due to absence of caution among peers, gender-based violence, lack of any symptoms associated with risk of HIV, and present bias towards immediate benefits of risky behaviors.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Coping ability</bold> 
                                <italic toggle="yes">includes user&#x2019;s ability to deal optimally with negative consequences of HIV prevention</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">User requires ability to deal with stigma, fear of judgement and shame, anticipated disruption of normal life routines in pursuing prevention, side-effects, and privacy violations</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Control 
                                <italic toggle="yes">includes the ability of the user to use prevention products</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Control over prevention decisions related to HIV prevention is limited by low negotiation power in relationships in the case of adolescent girls and young women, anticipated violence for adolescent girls and young women and female sex workers, mental health and inebriation.</td>
                        </tr>
                    </tbody>
                </table>
            </table-wrap>
            <sec>
                <title>Relevance</title>
                <p>Habits surrounding HIV prevention, such as finding an appropriate prevention method, or being aware of vulnerabilities that make one susceptible to HIV, are seldom consistent or widespread among at-risk populations. One of the factors influencing this is the relevance of HIV prevention to the individual. HIV prevention has been observed to be a low priority among adolescent girls and young women, and among men who have sex with men, who may instead prioritize economic needs and opportunities, safety from violence, and managing their familial and social relationships
                    <sup>
                        <xref ref-type="bibr" rid="ref-8">8</xref>,
                        <xref ref-type="bibr" rid="ref-9">9</xref>
                    </sup>. Furthermore, a dominant mental model that one seeks medical help only when sick limits the relevance of prevention preparedness, as studies from Malawi and Rwanda among female sex workers and men who have sex with men have shown
                    <sup>
                        <xref ref-type="bibr" rid="ref-10">10</xref>,
                        <xref ref-type="bibr" rid="ref-11">11</xref>
                    </sup>. Strategies to make HIV prevention relevant include integrating HIV prevention services into other health services
                    <sup>
                        <xref ref-type="bibr" rid="ref-12">12</xref>
                    </sup>, and showing how HIV prevention serves other life goals: for example, women who have higher-order, long-term goals to become pregnant have been found more likely to adhere to oral pre-exposure prophylaxis (PrEP)
                    <sup>
                        <xref ref-type="bibr" rid="ref-13">13</xref>
                    </sup>.</p>
            </sec>
            <sec>
                <title>Risk saliency</title>
                <p>Prevention action is also impacted by limited risk saliency, meaning that preventing HIV may not be top-of-mind when people are making decisions about sexual behavior (for example, because a potential partner shows no symptoms of HIV, or the individual believes that HIV is a manageable disease, or they have more pressing priorities than HIV prevention). Respondents in studies in South Africa, Kenya and Nigeria were optimistic that they would not get infected with HIV, and continued to engage in risky sexual behavior
                    <sup>
                        <xref ref-type="bibr" rid="ref-14">14</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-16">16</xref>
                    </sup>. Limited risk saliency is also influenced by present bias &#x2013; the tendency to prioritize perceived short-term gains at the cost of long-term outcomes
                    <sup>
                        <xref ref-type="bibr" rid="ref-17">17</xref>
                    </sup>.</p>
                <p>Social norms also contribute to a suboptimal risk assessment. Young people find little or low concern for safety around HIV among their peers, and this can negatively affect their own risk perception
                    <sup>
                        <xref ref-type="bibr" rid="ref-18">18</xref>
                    </sup>. Particularly among men, stereotypes surrounding masculinity drive emotional suppression that can hinder information-seeking and support, thus affecting adequate assessment of HIV risks
                    <sup>
                        <xref ref-type="bibr" rid="ref-19">19</xref>
                    </sup>. For adolescent girls and young women and female sex workers, harmful gender norms lead to a discounting of the risk originating from gender-based violence, even though this places individuals at higher risk of HIV
                    <sup>
                        <xref ref-type="bibr" rid="ref-20">20</xref>
                    </sup>.</p>
                <p>Another factor is that individuals generally take in HIV messages at times when they are not engaging in sexual behavior. In this &#x201c;cold&#x201d; state, deliberation on risks and benefits is optimally rational. But settings where unsafe risky behaviors take place often do not allow for optimal rational evaluation of risks and benefits. In this emotionally activated &#x201c;hot&#x201d; state, heuristics (mental short-cuts) are used for risk assessment. HIV prevention programs for adolescent girls and young women and men who have sex with men generally take place in out-of-context and safe (i.e. &#x201c;cold state&#x201d;) settings
                    <sup>
                        <xref ref-type="bibr" rid="ref-17">17</xref>
                    </sup>, but this may not equip them to perceive and accurately evaluate HIV risk at the time of sexual contact.</p>
            </sec>
            <sec>
                <title>Coping ability</title>
                <p>Individuals may experience discomfort, fear and anxiety while exploring HIV prevention options. An inability to cope with these negative emotions impacts the uptake of prevention products and services. Fear of stigmatization is a significant barrier. In sub-Saharan Africa, fear of disclosing test results was driven by normative expectations of social ostracization and partner abandonment, leading to avoidance of healthcare facilities and affecting uptake of HIV testing
                    <sup>
                        <xref ref-type="bibr" rid="ref-21">21</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-24">24</xref>
                    </sup>. These fears are disproportionately experienced by key populations
                    <sup>
                        <xref ref-type="bibr" rid="ref-25">25</xref>,
                        <xref ref-type="bibr" rid="ref-26">26</xref>
                    </sup>.</p>
                <p>Similar reactions have also been associated with PrEP, which is often conflated in popular perception with ART, meaning that a person who is taking PrEP for HIV prevention may be mistakenly perceived as already infected with HIV. Men who have sex with men and young people, including adolescent girls and young women in Uganda, Zimbabwe, and South Africa, often encounter negative attitudes when seen to be using PrEP and are subjected to stigmatization
                    <sup>
                        <xref ref-type="bibr" rid="ref-27">27</xref>,
                        <xref ref-type="bibr" rid="ref-28">28</xref>
                    </sup>. For female sex workers, using HIV prevention products can signal that they are sex workers, leading to potential police harassment and social ostracization
                    <sup>
                        <xref ref-type="bibr" rid="ref-29">29</xref>
                    </sup>. A review of studies found that adolescent girls and young women&#x2019;s uptake of condoms is affected by a fear that if they ask their partners to use a condom, they will themselves be judged as promiscuous and unfaithful
                    <sup>
                        <xref ref-type="bibr" rid="ref-26">26</xref>
                    </sup>.</p>
                <p>Fear of disruption in normal life and the perceived impact upon one&#x2019;s sex life affect an individual&#x2019;s decisions around prevention. In South Africa, Nigeria, Kenya, and Zambia, condom use was associated with loss of pleasure due to the absence of &#x201c;skin-to-skin&#x201d; contact during protected sex
                    <sup>
                        <xref ref-type="bibr" rid="ref-30">30</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-32">32</xref>
                    </sup>.</p>
                <p>Fear of side-effects is a critical influencing factor. Pregnant women, men who have sex with men and transgender women in South Africa most frequently cited side-effects as the reason for stopping their use of PrEP during a one-year course, even though the side-effects monitored in the study were small
                    <sup>
                        <xref ref-type="bibr" rid="ref-33">33</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-35">35</xref>
                    </sup>. In a qualitative study of adolescent girls and young women in Uganda, side-effects were also the main reason reported for stopping PrEP after 6 months of use
                    <sup>
                        <xref ref-type="bibr" rid="ref-36">36</xref>
                    </sup>. For the dapivirine vaginal ring (DVR, a silicone ring inserted in the vagina that releases an antiretroviral drug over a four-week period), perceived ring interference with sex, menstrual cycles, or potential harm to the vaginal environment have been expressed as concerns
                    <sup>
                        <xref ref-type="bibr" rid="ref-37">37</xref>
                    </sup>. Coping potential is also inadequate when it comes to anticipated pain. Corroborating a meta-analysis of the uptake of CAB-LA (a long-lasting injectable HIV prevention drug), a study conducted in Cape Town found that fear of the pain of injections impacted treatment uptake
                    <sup>
                        <xref ref-type="bibr" rid="ref-38">38</xref>,
                        <xref ref-type="bibr" rid="ref-39">39</xref>
                    </sup>.</p>
                <p>mHealth interventions in Ghana and South Africa, have helped reduce the stigma and anticipated discrimination associated with in-person testing, and signing confidentiality agreements has helped enhance patient satisfaction and trust within clinics
                    <sup>
                        <xref ref-type="bibr" rid="ref-40">40</xref>,
                        <xref ref-type="bibr" rid="ref-41">41</xref>
                    </sup>. The confidentiality of HIV self-testing (HIVST), and control over PrEP use, are further enablers that combat fear of judgement. HIVST alleviates issues around lack of privacy and trustworthiness of providers
                    <sup>
                        <xref ref-type="bibr" rid="ref-42">42</xref>
                    </sup>. The provision of channels for HIVST other than physical stores has also shown success at improving self-testing, such as the rollout of self-screening at Central Chronic Medicines Dispensing and Distribution points (CCMDD) in South Africa
                    <sup>
                        <xref ref-type="bibr" rid="ref-43">43</xref>
                    </sup>. Community-focused interventions have helped promote effective use of PrEP, condoms, and HIV testing. These primarily seek to raise community awareness to help reduce stigma, along with peer support and educators who help the individual conduct HIVST or cope with taking PrEP
                    <sup>
                        <xref ref-type="bibr" rid="ref-44">44</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-46">46</xref>
                    </sup>.</p>
                <p>DVR could help address barriers to adherence seen with oral PrEP since it does not require regular daily uptake thus reducing fear of stigma
                    <sup>
                        <xref ref-type="bibr" rid="ref-47">47</xref>
                    </sup>. Early trials have found that DVR has been well tolerated by women, side-effects are low, and adherence and reported desire for continued use is high
                    <sup>
                        <xref ref-type="bibr" rid="ref-48">48</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-50">50</xref>
                    </sup>. When given a choice between oral PrEP and DVR, two-thirds of adolescent girls and young women in the REACH program in South Africa, Zimbabwe, and Uganda chose DVR
                    <sup>
                        <xref ref-type="bibr" rid="ref-51">51</xref>
                    </sup>.</p>
            </sec>
            <sec>
                <title>Control</title>
                <p>Though there has been considerable success in improving the range of choice when it comes to HIV prevention, exercising effective choice has not progressed at the same pace. Lack of individual agency, a sense of control,  to negotiate use of HIV prevention products and services remains a significant barrier. Agency is affected by factors such as gender norms, violence, and mental health.</p>
                <p>Women may be at risk of violence from sexual partners and have little power to negotiate the use of condoms. Female sex workers in South Africa and Ethiopia report a tradeoff between asking a client to use a condom during sex and remaining safe from violence from the client, in which they will prioritize their immediate safety
                    <sup>
                        <xref ref-type="bibr" rid="ref-52">52</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-54">54</xref>
                    </sup>. Adolescent girls and young women across sub-Saharan Africa who may face violence or be unable to safely ensure condom use during sex have therefore expressed greater interest in PrEP to protect themselves from HIV
                    <sup>
                        <xref ref-type="bibr" rid="ref-55">55</xref>,
                        <xref ref-type="bibr" rid="ref-56">56</xref>
                    </sup>. Engaging partners in HIV prevention can improve risk evaluation within relationships. In the case of stable older relationships, partner engagement has improved last reported use of condom and led to a reduction in self-reported violence
                    <sup>
                        <xref ref-type="bibr" rid="ref-57">57</xref>
                    </sup>.</p>
                <p>Poor mental health or inebriation may also reduce the ability to engage in prevention decision-making. Depression has been associated with lower adherence to PrEP and to ART
                    <sup>
                        <xref ref-type="bibr" rid="ref-58">58</xref>
                    </sup>. Women in East Africa, South Africa, Kenya, and Uganda who were depressed had lower adherence to PrEP
                    <sup>
                        <xref ref-type="bibr" rid="ref-59">59</xref>,
                        <xref ref-type="bibr" rid="ref-60">60</xref>
                    </sup>, but depression did not impact PrEP adherence among men in East Africa or women in Uganda
                    <sup>
                        <xref ref-type="bibr" rid="ref-58">58</xref>,
                        <xref ref-type="bibr" rid="ref-59">59</xref>
                    </sup>.</p>
            </sec>
        </sec>
        <sec>
            <title>Interaction level</title>
            <p>The decision to take up HIV prevention products and services is made via one or more interactions (summarized in 
                <xref ref-type="table" rid="T2">Table 2</xref>) with other people. These may occur during demand mobilization campaigns, partner/support system engagement programs, peer outreach, or while receiving HIV prevention services at health facilities. Whether these interactions address their specific needs, involve supportive providers, and engage other people in the individual&#x2019;s ecosystem, will shape the individual&#x2019;s prevention decisions.</p>
            <table-wrap id="T2" orientation="portrait" position="anchor">
                <label>Table 2. </label>
                <caption>
                    <title>Summary table for interaction level of the user ecosystem.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="2" rowspan="1">
                                <italic toggle="yes">Interaction level includes the various interactions &#x2013; with family and friends, health system, access points, media and communications, etc. &#x2013; that a user is involved in while making the decision or action to undertake prevention</italic>
                            </th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Catering to multiple needs</bold> 
                                <italic toggle="yes">includes meeting an array of needs of users not limited to HIV but that directly or indirectly influence HIV prevention</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Users harbor multiple needs manifesting from different identities they associate themselves with, that go beyond HIV prevention and which are often not considered, resulting in inappropriate prevention-related messaging, need for delivery interventions such as DSD, service integration etc.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Availability of supportive</bold> stakeholders includes 
                                <italic toggle="yes">critical influencers in a user&#x2019;s ecosystem affecting HIV prevention decisions</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Users need/search for support from their close ties (family, peers) and service providers during uptake of prevention services and fear abandonment, judgement, or/and ostracization.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Building engaged interactions</bold> 
                                <italic toggle="yes">includes promoting active participation of partners, family and peers in user&#x2019;s prevention decision and journey</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">User&#x2019;s ecosystem needs to be constantly and meaningfully engaged, be it peers, partners, or family. Enhanced outreach programs, partner engagement during antenatal visits, partner-focused programs such as counselling have shown to positively influence uptake of HIV prevention.</td>
                        </tr>
                    </tbody>
                </table>
            </table-wrap>
            <sec>
                <title>Catering to multiple needs</title>
                <p>Interactions involving communication campaigns, and service delivery by providers, face several challenges, one of which is that at-risk populations are often subjected to a blanket approach, be it in product promotion or behavior change communications. This leads to non-alignment of HIV prevention with the precise identities and needs of users. For instance, messaging aimed broadly at men who have sex with men might not resonate with men who identify specifically as gay, and communication targeting an adolescent girl might not be relevant to a young woman
                    <sup>
                        <xref ref-type="bibr" rid="ref-61">61</xref>
                    </sup>. This mismatch between identities and communication content can increase avoidance of product communication messages and further isolate individuals from seeking appropriate HIV prevention opportunities. Communication on HIV prevention and risk also often does not consider how identities can shift within the same individual, e.g. HIV-negative to HIV-positive, or from not being pregnant to being pregnant
                    <sup>
                        <xref ref-type="bibr" rid="ref-62">62</xref>
                    </sup>. Each of these identities carry with it a different set of needs and vulnerabilities, which if not addressed or considered can lead to individuals being unable to appreciate their level of risk.</p>
                <p>Interactions between user and providers are also hampered by service-related limitations such as product availability, facility hours, and staff shortages. A notable barrier at this level is low product availability. As of 2020, there was a shortage of 3.3 billion condoms distributed in eastern and southern Africa
                    <sup>
                        <xref ref-type="bibr" rid="ref-63">63</xref>
                    </sup>, and PrEP was only widely available in five countries&#x2019; national public health systems in the sub-region
                    <sup>
                        <xref ref-type="bibr" rid="ref-64">64</xref>
                    </sup>. In South Africa, provincial-level departments of health experience frequent shortages in PrEP supplies, which is a substantial barrier for uptake among pregnant and postpartum women in Cape Town
                    <sup>
                        <xref ref-type="bibr" rid="ref-34">34</xref>,
                        <xref ref-type="bibr" rid="ref-65">65</xref>
                    </sup>. A lack of testing kits has also been seen across sub-Saharan Africa
                    <sup>
                        <xref ref-type="bibr" rid="ref-23">23</xref>
                    </sup>.</p>
                <p>Key populations have varying needs and barriers when it comes to accessing and using prevention methods such as PrEP, condoms, and HIV testing, and current service delivery models may therefore not work for all of them. Differentiated service delivery (DSD) has been successful in adapting service delivery to the differentiated needs and vulnerabilities of the individuals being served, such as through fast-tracked collection of HIV medication, community pick-up points or home delivery, multi-month dispensing and frequent refill options, as well as adherence support groups and extended clinic hours
                    <sup>
                        <xref ref-type="bibr" rid="ref-66">66</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-70">70</xref>
                    </sup>. DSD has primarily been used to promote ART adherence, but there is a growing focus on the need and opportunity to expand this to other prevention services such as PrEP and HIV testing where barriers to access remain pressing
                    <sup>
                        <xref ref-type="bibr" rid="ref-71">71</xref>
                    </sup>.</p>
                <p>A recent shift in DSD is toward integration of services
                    <sup>
                        <xref ref-type="bibr" rid="ref-12">12</xref>,
                        <xref ref-type="bibr" rid="ref-72">72</xref>,
                        <xref ref-type="bibr" rid="ref-73">73</xref>
                    </sup>. HIV can be integrated with services for non-communicable diseases and TB, as well as for STI testing, family planning, and gender-affirming hormone therapy
                    <sup>
                        <xref ref-type="bibr" rid="ref-74">74</xref>,
                        <xref ref-type="bibr" rid="ref-75">75</xref>
                    </sup>. For example, PrEP is being integrated into family planning services, antenatal clinics, and post-abortion care services in Kenya
                    <sup>
                        <xref ref-type="bibr" rid="ref-74">74</xref>
                    </sup>. Other health services can also be integrated into existing HIV services, such as offering hypertension and diabetes management at ART adherence clubs
                    <sup>
                        <xref ref-type="bibr" rid="ref-76">76</xref>
                    </sup>. There is an opportunity for greater integration of HIV services and mental health, especially given that vulnerabilities such as depression and substance use impact HIV prevention adherence, although there is currently little evidence of integration in this area.</p>
                <p>Service integration as part of policy, as well as program design, can support both DSD as well as combination prevention, i.e. the combining of biomedical, behavioral, and structural interventions
                    <sup>
                        <xref ref-type="bibr" rid="ref-77">77</xref>
                    </sup>. This may be especially important for improving service delivery for key populations, as they face complex and varied barriers such as legal limitations, social stigma and provider bias, gender-based violence and social and economic inequalities
                    <sup>
                        <xref ref-type="bibr" rid="ref-77">77</xref>,
                        <xref ref-type="bibr" rid="ref-78">78</xref>
                    </sup>. An analysis of studies to promote condom use among female sex workers in sub-Saharan Africa found that combination prevention was highly effective. Effective interventions included educating female sex workers and creating supportive work environments, while others involved peer support combined with free condoms provided through peers as well as health providers
                    <sup>
                        <xref ref-type="bibr" rid="ref-79">79</xref>
                    </sup>.</p>
            </sec>
            <sec>
                <title>Availability of supportive stakeholders</title>
                <p>Health systems and programs have found it difficult to involve crucial stakeholders like family and religious leaders in HIV communication efforts because of prevailing social norms stigmatizing key populations. The inability to appeal to the strong ties of family and religion often prevents programs and providers from leveraging credible, trustworthy sources of information and support in outreach to key populations.</p>
                <p>Healthcare providers are often biased against key populations and are sometimes ignorant of their obligation to maintain the confidentiality of their patients
                    <sup>
                        <xref ref-type="bibr" rid="ref-80">80</xref>
                    </sup>. A study in Ghana found providers preaching religious teachings to men who have sex with men seeking treatment, and sometimes outright ignoring them
                    <sup>
                        <xref ref-type="bibr" rid="ref-81">81</xref>
                    </sup>. Negative attitudes among healthcare providers in South Africa hinder the promotion and delivery of PrEP to young people
                    <sup>
                        <xref ref-type="bibr" rid="ref-82">82</xref>
                    </sup>. Other studies in sub-Saharan Africa have also highlighted how provider bias obstructs treatment access for young people, including adolescent girls and young women, who are subjected to unnecessary and demeaning conditions, impeding their reproductive health choices
                    <sup>
                        <xref ref-type="bibr" rid="ref-83">83</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-85">85</xref>
                    </sup>.</p>
                <p>One way to enable more open and stigma-free interactions between key populations and healthcare providers is sensitivity training to help providers better understand the behaviors and needs of key populations
                    <sup>
                        <xref ref-type="bibr" rid="ref-74">74</xref>
                    </sup>. Kenya and Zimbabwe&#x2019;s national policies suggest the use of the &#x201c;train the trainer&#x201d; model, in which healthcare providers train other providers, creating a snowball effect and speeding up the de-stigmatization of healthcare settings
                    <sup>
                        <xref ref-type="bibr" rid="ref-86">86</xref>
                    </sup>. In Kenya, men who have sex with men who are HIV+ being engaged through culturally trained peer educators have improved willingness to be engaged in treatment
                    <sup>
                        <xref ref-type="bibr" rid="ref-87">87</xref>
                    </sup>. Studies in Tanzania and Uganda showed that uptake of HIV prevention strategies rose to almost 70% when endorsed by religious leaders
                    <sup>
                        <xref ref-type="bibr" rid="ref-88">88</xref>,
                        <xref ref-type="bibr" rid="ref-89">89</xref>
                    </sup>. Support groups and peer educators and mentors have been seen to improve PrEP adherence for female sex workers, adolescent girls and young women, and men who have sex with men in Kenya
                    <sup>
                        <xref ref-type="bibr" rid="ref-64">64</xref>,
                        <xref ref-type="bibr" rid="ref-90">90</xref>
                    </sup>.</p>
            </sec>
            <sec>
                <title>Building engaged interactions</title>
                <p>One approach to engaging individuals about HIV prevention is to involve key stakeholders within their ecosystem, including peers, partners, support groups, etc. The &#x201c;enhanced peer outreach approach&#x201d; capitalizes on key population individuals&#x2019; higher trust in their peers, leading to better engagement with HIV awareness programs, promoting safer sexual practices and increasing the probability that the individual attains the desired risk perception
                    <sup>
                        <xref ref-type="bibr" rid="ref-91">91</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-93">93</xref>
                    </sup>. However, only limited studies have been done to show if peer led outreach impacts risk perception enough to alter risky sexual behaviors.</p>
                <p>Women visiting antenatal and postpartum care in Kenya, Malawi, and Uganda have been given HIVST kits to share with their partners, which has improved testing uptake among these men
                    <sup>
                        <xref ref-type="bibr" rid="ref-94">94</xref>,
                        <xref ref-type="bibr" rid="ref-95">95</xref>
                    </sup>. Community-led monitoring and peer support has also shown to promote HIVST
                    <sup>
                        <xref ref-type="bibr" rid="ref-46">46</xref>
                    </sup>.</p>
                <p>Another ecosystem-rooted engagement approach aims to engage men/partners in addressing vulnerabilities resulting from partner violence and harmful gender norms. Inequitable gender norms negatively impact women&#x2019;s access to care, levels of physical and sexual violence and condom use. In stable relationships among older couples, male-partner engagement has improved the reported use of a condom on the most recent occasion of sex, and led to a reduction in self-reported violence
                    <sup>
                        <xref ref-type="bibr" rid="ref-57">57</xref>
                    </sup>. In Kenya, the &#x201c;better family&#x201d; intervention using couples counselling on HIV testing and care showed positive couple communication and efficacy to act around HIV
                    <sup>
                        <xref ref-type="bibr" rid="ref-96">96</xref>
                    </sup>. For adolescent girls and young women, school-based programs on HIV and violence reduction have shown positive results in terms of reduced acceptability to partner violence and decrease in multiple partners
                    <sup>
                        <xref ref-type="bibr" rid="ref-97">97</xref>
                    </sup>.</p>
                <p>Support groups and peer educators and mentors have improved PrEP adherence for female sex workers, adolescent girls and young women, and men who have sex with men in Kenya
                    <sup>
                        <xref ref-type="bibr" rid="ref-64">64</xref>,
                        <xref ref-type="bibr" rid="ref-90">90</xref>
                    </sup>. DSD interventions that focus on flexible adherence support and enable more frequent visits may be particularly beneficial for adolescent girls and young women
                    <sup>
                        <xref ref-type="bibr" rid="ref-98">98</xref>
                    </sup>. There is also the potential to integrate social media into these services, such as the use of WhatsApp&#x00a9; chat groups for adherence clubs
                    <sup>
                        <xref ref-type="bibr" rid="ref-99">99</xref>
                    </sup>.</p>
                <p>It can be important to differentiate between the communication preferences of different groups. A study in Nigeria showed that that female sex workers preferred face-to-face interactions, phone calls, and SMS for information regarding PrEP and HIVST, while men who have sex with men preferred digital platforms like WhatsApp, Facebook&#x00a9;, Instagram&#x00a9;, and Twitter&#x00a9;
                    <sup>
                        <xref ref-type="bibr" rid="ref-100">100</xref>
                    </sup>.</p>
            </sec>
        </sec>
        <sec>
            <title>Systemic level</title>
            <p>In addition to the individual interactional levels, where the individual is firmly involved and holds a central place, there is a systemic level surrounding the individual. This is the environment in which individuals make prevention decisions and interact with others for prevention-related products and services. Four key factors (
                <xref ref-type="table" rid="T3">Table 3</xref>) at this level impacting HIV-prevention behaviors are legal barriers, societal constraints involving dominant social norms, economic vulnerabilities, and education.</p>
            <table-wrap id="T3" orientation="portrait" position="anchor">
                <label>Table 3. </label>
                <caption>
                    <title>Summary table for systemic level of the user ecosystem.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="2" rowspan="1" valign="top">
                                <italic toggle="yes">Systemic level includes structural factors that significantly shape the ecosystem and include culture, political institutions, programs, and policies.</italic>
                            </th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Legal barriers</bold> 
                                <italic toggle="yes">include laws and policies enacted in a country that influence uptake of HIV prevention</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Legal barriers to HIV prevention consist of criminalization of same-sex marriage, LGBTQ people, and sex workers. Additionally, policies surrounding legal consent for adolescents, and lack of law enforcement protocols for gender and sexual violence, impede uptake of HIV prevention and hamper engagement with at-risk populations.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Societal constraints</bold> 
                                <italic toggle="yes">include cultural and social beliefs surrounding gender, sexual behaviors, and HIV.</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">HIV prevention is negatively impacted by harmful gender norms, stigma that often perpetrate fear and judgement, and intimate partner violence.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Economic vulnerabilities</bold> 
                                <italic toggle="yes">include the disadvantageous financial and material circumstances of users.</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Economic difficulties arise due to unemployment, poverty, and gender inequity, resulting in lower uptake of prevention products, participation in HIV prevention programs, and prioritization of other needs over HIV prevention.</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>Education</bold> 
                                <italic toggle="yes">includes factors associated with educational attainment and elements of schooling relevant for HIV prevention</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Education is a key determinant for HIV awareness and HIV prevention and is driven by the proportion of the population (girls in particular) enrolled in primary schools, the presence or absence of a comprehensive sexual education curriculum, school continuity, and risk-literacy programs/policies</td>
                        </tr>
                    </tbody>
                </table>
            </table-wrap>
            <sec>
                <title>Legal barriers</title>
                <p>Structural barriers lead to inadequate access to healthcare services for key populations, and insensitive service delivery. Laws criminalizing the identity or behaviors of key populations constitute a key barrier
                    <sup>
                        <xref ref-type="bibr" rid="ref-87">87</xref>
                    </sup>. A constraining legal environment leads to fear of &#x2013; and actual &#x2013; violence and harassment. This is evident for example in countries like Cameroon, Uganda, Nigeria, and Malawi, where criminalization limits the involvement of key populations in HIV prevention campaigns and access
                    <sup>
                        <xref ref-type="bibr" rid="ref-101">101</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-104">104</xref>
                    </sup>. Criminalizing sex work obstructs HIV prevention efforts, subjects sex workers to police harassment and sexual violence
                    <sup>
                        <xref ref-type="bibr" rid="ref-105">105</xref>,
                        <xref ref-type="bibr" rid="ref-106">106</xref>
                    </sup>, and undermines safe-sex negotiations with clients
                    <sup>
                        <xref ref-type="bibr" rid="ref-107">107</xref>
                    </sup>. Similarly, laws penalizing same-sex relationships contribute to stigma and discrimination, and hinder HIV prevention interventions, perpetuating the epidemic among men who have sex with men
                    <sup>
                        <xref ref-type="bibr" rid="ref-108">108</xref>
                    </sup>. Countries that have decriminalized same-sex relations, such as South Africa and Botswana, have seen greater rates of testing and access to treatment among men who have sex with men
                    <sup>
                        <xref ref-type="bibr" rid="ref-78">78</xref>
                    </sup>.</p>
                <p>Sex workers in China and Uganda must avoid accepting condoms from health services due to concerns that condoms will be used as evidence of sex workers&#x2019; occupation, which is illegal and can lead to imprisonment or even the death penalty
                    <sup>
                        <xref ref-type="bibr" rid="ref-109">109</xref>,
                        <xref ref-type="bibr" rid="ref-110">110</xref>
                    </sup>. Studies conducted in Ethiopia, Kenya, China, and India found evidence of violence by law enforcement against sex workers, with police demanding condomless sex. However, most of the evidence towards working on mitigating violence from law enforcement has been concentrated in community-led interventions and mobilization of female sex workers and men who have sex with men to take legal action
                    <sup>
                        <xref ref-type="bibr" rid="ref-106">106</xref>
                    </sup>. There has been limited evidence of state-level policy interventions acknowledging the existence of violence and prohibiting its perpetration on female sex workers and men who have sex with men
                    <sup>
                        <xref ref-type="bibr" rid="ref-111">111</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-113">113</xref>
                    </sup>.</p>
                <p>Strict consent laws for medical services in countries like Uganda and Kenya make it difficult for adolescents to access prevention until they are 18. This is particularly worrying for adolescent girls and young women at heightened risk of HIV, since the only way to access treatment is through explicit consent from their parents or guardians, which can lead to violence and social ostracization
                    <sup>
                        <xref ref-type="bibr" rid="ref-114">114</xref>
                    </sup>. However, several countries are making strides in addressing consent laws. South Africa&#x2019;s reduction in the age of consent for medical services to 12 years saw significant increases in uptake of PrEP and HIV testing among teenagers
                    <sup>
                        <xref ref-type="bibr" rid="ref-115">115</xref>
                    </sup>. Tanzania also achieved comparable results after lowering the age to 12
                    <sup>
                        <xref ref-type="bibr" rid="ref-114">114</xref>
                    </sup>.</p>
            </sec>
            <sec>
                <title>Societal constraints</title>
                <p>Harmful gender norms make it difficult, especially for women, to exercise choice and agency to assess and access relevant HIV prevention opportunities. In Kenya, women who anticipate male-partner stigma or violence are more than twice as likely to refuse HIV testing
                    <sup>
                        <xref ref-type="bibr" rid="ref-116">116</xref>
                    </sup>. In Uganda, some women&#x2019;s decision not to initiate PrEP was due to anticipated violence from their partners
                    <sup>
                        <xref ref-type="bibr" rid="ref-117">117</xref>,
                        <xref ref-type="bibr" rid="ref-118">118</xref>
                    </sup>. A study conducted in South Africa found that intimate partner violence and fear this can result in postpartum women not feeling confident enough to request condom use
                    <sup>
                        <xref ref-type="bibr" rid="ref-119">119</xref>
                    </sup>. Female sex workers who have been recent victims of violence find it even more difficult to use condoms with their male intimate partners than with their clients
                    <sup>
                        <xref ref-type="bibr" rid="ref-120">120</xref>
                    </sup>.</p>
                <p>It has also been reported that men who endorse inequitable gender norms are less likely to take up HIV prevention products like condoms, or services like self-testing
                    <sup>
                        <xref ref-type="bibr" rid="ref-121">121</xref>
                    </sup>, as they fear it may be perceived as a sign of weakness or vulnerability
                    <sup>
                        <xref ref-type="bibr" rid="ref-122">122</xref>
                    </sup>. Prevailing gender norms, which may cause healthcare providers to hold negative attitudes, often discourage at-risk populations from openly discussing sexual health concerns and accessing appropriate care, as seen in studies from Malawi and Mozambique
                    <sup>
                        <xref ref-type="bibr" rid="ref-96">96</xref>,
                        <xref ref-type="bibr" rid="ref-123">123</xref>
                    </sup>. Gender norms that drive inequity contribute to a lack of agency for sex workers in negotiating condom use or asserting their sexual health needs
                    <sup>
                        <xref ref-type="bibr" rid="ref-124">124</xref>
                    </sup>. In South Africa, the sex worker organizations SWEAT and Sisonke run a national 24-hour toll-free helpline staffed by trained sex worker counsellors. The helpline addresses concerns including violence and police abuse, offering telephonic and face-to-face counselling. Referrals to paralegals and partner organizations are provided when needed
                    <sup>
                        <xref ref-type="bibr" rid="ref-106">106</xref>
                    </sup>.</p>
            </sec>
            <sec>
                <title>Economic vulnerabilities</title>
                <p>Poverty and unemployment make at-risk populations, particularly women, vulnerable to health challenges due to increased risk-taking behavior. In the face of economic needs, many women resort to transactional sex to sustain their livelihoods, and young girls are often coerced into sexual activities with older men to survive. Studies across South Africa, Kenya, Malawi, and Uganda showed that people with a low socio-economic status (SES) reported significantly lower HIV testing uptake as well as lower usage of condoms than those with a high SES
                    <sup>
                        <xref ref-type="bibr" rid="ref-125">125</xref>&#x2013;
                        <xref ref-type="bibr" rid="ref-127">127</xref>
                    </sup>. Low economic status has been associated with earlier first sexual experience, lower condom use during most recent sex, having multiple sex partners, increased chances that the first sex act is non-consensual, and a greater likelihood of having had transactional sex or physically forced sex
                    <sup>
                        <xref ref-type="bibr" rid="ref-128">128</xref>
                    </sup>. Programs with an economic-support component or cash-transfer schemes have been seen to lower risky sexual activity
                    <sup>
                        <xref ref-type="bibr" rid="ref-128">128</xref>
                    </sup>. Conditional cash-transfer programs like the 
                    <italic toggle="yes">zomba</italic> cash experiment in Malawi boosted the acceptability of HIV prevention products among adolescent girls and young women
                    <sup>
                        <xref ref-type="bibr" rid="ref-129">129</xref>
                    </sup>. In Tanzania, high-value cash transfers lowered STI prevalence through increased prevention product uptake
                    <sup>
                        <xref ref-type="bibr" rid="ref-130">130</xref>
                    </sup>.</p>
                <p>Reduced funding, mostly for condoms and VMMC, along with challenges within health systems, including inefficient supply chain design for HIV products in southern and eastern Africa, limits programs&#x2019; ability to effectively reach and promote HIV prevention among key populations
                    <sup>
                        <xref ref-type="bibr" rid="ref-131">131</xref>,
                        <xref ref-type="bibr" rid="ref-132">132</xref>
                    </sup>. The efficiency of healthcare delivery systems also structurally impacts the availability and coverage of HIV prevention and treatment products. In Ethiopia, for example, poor supply chain management has led to stock-outs as well as poor data-keeping, and high rates of wastage
                    <sup>
                        <xref ref-type="bibr" rid="ref-133">133</xref>
                    </sup>. Uganda mitigated similar problems through training and on-site mentorship for its logistics management information systems, which reduced stock outages and improved record-keeping
                    <sup>
                        <xref ref-type="bibr" rid="ref-134">134</xref>
                    </sup>. Programmatic investments such as EpiC (Meeting Targets and Maintaining Epidemic Control) and BioPIC (Biomedical Prevention Implementation Collaborative) aim to improve program implementation and management, and health information systems through collaboration with local partners.</p>
            </sec>
            <sec>
                <title>Education</title>
                <p>Education is a key structural determinant for awareness of HIV and demand mobilization. Increased education and higher levels of educational attainment have been shown to be linked to reduced HIV incidence and prevalence. In Botswana, each year of schooling has been associated with an 8.1 percentage-point drop in HIV incidence
                    <sup>
                        <xref ref-type="bibr" rid="ref-135">135</xref>
                    </sup>. Similarly, in Zimbabwe, among 15&#x2013;18-year-old girls, those who are enrolled in school are more than five times less likely to have HIV than those who have dropped out
                    <sup>
                        <xref ref-type="bibr" rid="ref-136">136</xref>
                    </sup>. Though enrollment into primary education has been increasing in the region, around 18% of girls in Kenya do not complete primary education
                    <sup>
                        <xref ref-type="bibr" rid="ref-137">137</xref>
                    </sup>. Limited access to education for young girls and no avenue for adults in at-risk populations is a barrier that has a significant impact on HIV prevention.</p>
                <p>The Ministry of Education in most countries has adopted comprehensive sexuality education (CSE) as a policy measure
                    <sup>
                        <xref ref-type="bibr" rid="ref-138">138</xref>
                    </sup>. This is a participatory, curriculum-based approach to equip children and young people with knowledge, skills, attitudes, and values that empower them. The curriculum covers the human body and development, sexual and reproductive health and rights, values, culture, and sexuality, relationships, gender, and diversity
                    <sup>
                        <xref ref-type="bibr" rid="ref-139">139</xref>
                    </sup>. In 2023, South Africa published a national HIV literacy framework to improve people&#x2019;s ability to use health information rather than just understanding it, to focus on &#x201c;well-informed&#x201d; decisions than &#x201c;appropriate&#x201d; ones, and to drive a public-health perspective among populations
                    <sup>
                        <xref ref-type="bibr" rid="ref-140">140</xref>
                    </sup>.</p>
            </sec>
        </sec>
        <sec sec-type="discussion">
            <title>Discussion</title>
            <p>An ecosystem lens for HIV prevention offers valuable insights into barriers and enablers at individual, interactional, and structural levels. This approach has aided policymakers and program managers in refining implementation strategies by leveraging knowledge of broader influences around a target beneficiary of HIV prevention products and services. Community-outreach initiatives, tailored behavioral interventions, comprehensive sexuality education, health system enhancements, and rights-based policy advocacy exemplify how this perspective informs program design.</p>
            <p>The ecosystem approach has also complemented the cascade strategy that has been applied to HIV treatment and prevention
                <sup>
                    <xref ref-type="bibr" rid="ref-141">141</xref>
                </sup>. Cascades are visual interpretations of data that help monitor service access and performance by identifying barriers and inefficiencies faced by target populations and developing actionable strategies to improve programs. Cascades, whether product-specific (for condoms, PrEP, HIV testing) or population-specific (for adolescent girls and young women, sex workers, men who have sex with men), help identify drop-off points where individuals are failing to progress to the next appropriate service, and the ecosystem perspective can then help develop interventions at different levels to address these drop-off points. Thus, parsing HIV prevention into ecosystem levels is useful to tackle the implementation challenges that programs face at different levels and to develop interventions
                <sup>
                    <xref ref-type="bibr" rid="ref-142">142</xref>
                </sup>.</p>
            <p>However, the ecosystem approach has limitations. It illuminates the factors underlying decision-making about HIV prevention &#x2013; the &#x201c;what&#x201d;, i.e., a descriptive understanding of the current state &#x2013; but does not fully explain the mechanisms driving this state over time. Without a temporal aspect, this creates a static view of the challenge. For instance, at the interaction level, availability of supportive stakeholders is an important factor, but an ecosystem lens does not explain exactly how supportive stakeholders enable or impede a user in making an HIV prevention-related decision, whether this happens at the moment of delivery or along a mental journey towards the decision. As another example, taking an ecosystem approach to designing interventions to improve an awareness program involving mass media can help understand who the important influencers or decision-makers are, what new product information users need, or what channel to leverage etc.  But none of these explain the mediating mechanism causing the influence.</p>
            <p>There is a need for an integrated approach to combine an understanding of the various factors at the different ecosystem levels with an awareness of some other interlocking and dynamic aspects of decision-making &#x2013; one that internalizes the inherent dynamic context in HIV prevention decision-making and can build on changing levels of perceived risk, product availability and usage (
                <xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
            <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                <label>Figure 1. </label>
                <caption>
                    <title>Illustrative view augmenting dynamic time-based context onto the static view of the ecosystem levels.</title>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://gatesopenresearch-files.f1000.com/manuscripts/17428/4bb176f2-5a39-44af-a9db-fbc398532197_figure1.gif"/>
            </fig>
            <p>As illustrated in 
                <xref ref-type="fig" rid="f1">Figure 1</xref>, an integrated approach can integrate the two components surrounding a HIV prevention decision &#x2013; time and ecosystem level. This enables the understanding that the influence of the three ecosystem levels at any given point of time is not the same, and this influence also varies with time. Variation within levels can be understood as differing effects of the numerous factors present at that level. For instance, a systemic level can have variable influence on the HIV prevention decision if the underlying factors for the level&#x2014;say, stigma and poverty&#x2014;change with respect to time. Hence a policy or law criminalizing same-sex marriage at a given point in time can increase the influence of systemic level on HIV prevention decisions, as compared with other levels (individual and interactional).</p>
            <p>Recently, the focus of HIV prevention has shifted towards self-care, defined by the World Health Organization as &#x201c;the ability of individuals, families, and communities to promote health, prevent disease, maintain health, and cope with illness and disability, with or without the support of a health worker&#x201d;
                <sup>
                    <xref ref-type="bibr" rid="ref-142">142</xref>
                </sup>. This paradigm shift requires moving beyond mere access and availability of HIV prevention products and services. Prevention-related decisions involve continuously varying risk perception, product availability and preferences, and desired prevention actions. Risk perception not only concerns an individual's attention but also drives the necessary intent to act. With advancements in product development, exploring users&#x2019; preferences is crucial for optimally allocating and positioning these products throughout their health-seeking journey. Traditionally, efforts have been focused on uptake and adherence&#x2014;regular use of prevention products&#x2014;but shifting towards effective use emphasizes selecting the right HIV prevention approach based on one&#x2019;s current circumstances, integrating optimal risk assessment and positive product preference. For instance, this might mean opting for PrEP when an individual perceives themselves to be at risk of HIV and has a positive outlook towards its use, devoid of stigma or cost barriers; or deciding against PrEP when the individual assesses their risk to be negligible. An integrated socio-ecological approach, grounded in extensive user research and appreciation of these dynamic contexts, can provide policymakers and program planners with critical insights to support appropriate choices and effective use of HIV prevention products, ensuring decisions are contextually relevant and sustainable across different levels within the ecosystem.</p>
        </sec>
        <sec sec-type="conclusions">
            <title>Conclusion</title>
            <p>Unlike treatment, HIV prevention necessitates multi-level and multi-point interventions, lacks immediate urgency for users, demands different product usage protocols based on the perception of risk, and involves a diverse population with varying needs, risks, and vulnerabilities. As HIV-related investments continue to benefit an increasing number of individuals, leading to a decline in overall incidence and prevalence, it becomes important to develop a more comprehensive approach for public-health practitioners to extend prevention services to key and at-risk populations to limit primary transmission. An approach incorporating the dynamic, time-contingent components of decision-making can offer insights to funders and policymakers to address ineffective program implementation and drop-off from uptake of prevention products and services.</p>
        </sec>
        <sec>
            <title>Disclaimer</title>
            <p>The views expressed in this article are those of the author(s). Publication in the Gates Open Journal does not imply endorsement by The Bill and Melinda Gates Foundation.</p>
        </sec>
    </body>
    <back>
        <sec sec-type="data-availability">
            <title>Data availability</title>
            <sec>
                <title>Underlying data</title>
                <p>No data associated with this article.</p>
            </sec>
        </sec>
        <ack>
            <title>Acknowledgments</title>
            <p>We acknowledge the support of Ms. Jill Gada and Mr. Rahul Porwal, who assisted the research team during this study.</p>
        </ack>
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    </back>
    <sub-article article-type="reviewer-report" id="report37948">
        <front-stub>
            <article-id pub-id-type="doi">10.21956/gatesopenres.17428.r37948</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Bhattacharjee</surname>
                        <given-names>Parinita</given-names>
                    </name>
                    <xref ref-type="aff" rid="r37948a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-3277-7693</uri>
                </contrib>
                <aff id="r37948a1">
                    <label>1</label>University of Manitoba, Manitoba, Canada</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>3</day>
                <month>10</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Bhattacharjee P</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport37948" related-article-type="peer-reviewed-article" xlink:href="10.12688/gatesopenres.16067.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This is an interesting article focusing on the demand for HIV prevention and sharing factors that may influence the uptake of HIV prevention products and services. The article prioritizes populations who are at risk of acquiring HIV. This is a timely article as we will be missing the 2025 global HIV prevention targets and have to rethink how we can increase the demand and utilization of HIV prevention products by populations that need them the most.</p>
            <p> </p>
            <p> However, I think the article would benefit more if the recommendations and next steps were clearer, with examples of how this framework can be used to address real-life problems. More emphasis on the application of the framework is needed. In the discussion section, the authors mention that this approach has aided policymakers and program managers in refining implementation strategies.... A few examples of such strategy revisions would be helpful.</p>
            <p> </p>
            <p> I also struggled to understand the dynamic time-based context and its integration into the static view of the ecosystem levels and its application. Again, the use of relevant examples to show how decision-making changes with or without the inclusion of dynamic time-based context may help.</p>
            <p>Does the article adequately reference differing views and opinions?</p>
            <p>Partly</p>
            <p>Are all factual statements correct, and are statements and arguments made adequately supported by citations?</p>
            <p>Yes</p>
            <p>Is the Open Letter written in accessible language?</p>
            <p>Yes</p>
            <p>Where applicable, are recommendations and next steps explained clearly for others to follow?</p>
            <p>Partly</p>
            <p>Is the rationale for the Open Letter provided in sufficient detail?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>HIV prevention, key populations</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment3753-37948">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Gantayat</surname>
                            <given-names>Nishan</given-names>
                        </name>
                        <aff>Behavioral Science, Not Applicable, Mumbai, Maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>22</day>
                    <month>11</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <italic>Authors Response: Thank you for the feedback. We have noted this and have made changes to the paper to elaborate more on the dynamism associated with the framework with real-life HIV prevention-related decisions as examples. Also we have chosen to be specific on the strategic implications of this integrated approach by concentrating on self-care. Changes have been made to the discussion section to include these aspects.&#x00a0;</italic>
                </p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report37951">
        <front-stub>
            <article-id pub-id-type="doi">10.21956/gatesopenres.17428.r37951</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Schaefer</surname>
                        <given-names>Robin</given-names>
                    </name>
                    <xref ref-type="aff" rid="r37951a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-4733-4692</uri>
                </contrib>
                <aff id="r37951a1">
                    <label>1</label>Forum for Collaborative Research, University of California Berkeley, Berkeley, California, USA</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>28</day>
                <month>9</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Schaefer R</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport37951" related-article-type="peer-reviewed-article" xlink:href="10.12688/gatesopenres.16067.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>I thank the editors for inviting me to review this interesting article on an ecosystem-based approach to understanding HIV prevention decision-making. The authors provide a systematic overview of the range of factors influencing uptake of prevention products, at the individual, social, and structural level, and propose a dynamic framework to understand how these factors interact. The article is well-written and comprehensive. However, as noted in one of the comments below, the article needs to be situated in the broader literature on this topic and justify its added value. Below I provide further suggestions to improve the article. Once these are addressed, the article can make a useful contribution to the literature and will likely be of interest to a broad range of readers.</p>
            <p> </p>
            <p> Abstract 
                <list list-type="bullet">
                    <list-item>
                        <p>In the second paragraph, the authors mention that they focus on &#x201c;demand for HIV prevention&#x201d;. I think the article is more broadly about &#x201c;factors that influence uptake of prevention products&#x201d;, not just demand-side factors.</p>
                    </list-item>
                </list> Introduction 
                <list list-type="bullet">
                    <list-item>
                        <p>First paragraph: This article is focused on HIV prevention, so it may be more appropriate to start the article with a focus on HIV prevention target. The 95-95-95 targets are about HIV treatment. While treatment-as-prevention is an important concept, we know that there are limits to its impact on HIV incidence, so primary prevention is most critical.</p>
                    </list-item>
                    <list-item>
                        <p>Second paragraph: &#x201c;CAB-LA&#x201d; is a more commonly used acronym for long-acting injectable cabotegravir. The authors should spell this out on first occurrence. Furthermore, CAB-LA should not be described as &#x201c;ART&#x201d; (although it is an antiretroviral drug). Finally, the authors may want to add information on oral PrEP and nuance the statement on new PrEP products as these are not yet widely available.</p>
                    </list-item>
                    <list-item>
                        <p>Third paragraph: Similar to the comment above, the focus should not be on an HIV treatment target (90-90-90).</p>
                    </list-item>
                    <list-item>
                        <p>Seventh paragraph: Since the authors note that they focus on the prevention landscape in eastern and southern Africa, they may want to include some general background on the region, such as HIV incidence and HIV prevention efforts and progress (including among key populations).</p>
                    </list-item>
                </list> Individual level 
                <list list-type="bullet">
                    <list-item>
                        <p>Table 1: &#x201c;Control&#x201d; in the last row should also be in bold.</p>
                    </list-item>
                    <list-item>
                        <p>Table 1: The statement in the &#x201c;Relevance&#x201d; section requires a reference or needs to be written in a more general sense.</p>
                    </list-item>
                    <list-item>
                        <p>Risk saliency section, third paragraph: Here, and elsewhere, avoid language around &#x201c;risky sexual behaviour&#x201d;. This language can be stigmatizing. More neutral language of &#x201c;behaviour associated with increased HIV acquisition risk&#x201d; or something similar should be adopted.</p>
                    </list-item>
                    <list-item>
                        <p>Coping ability section: Towards the end of this section, different PrEP products are described. This should be included in the introduction of the article.</p>
                    </list-item>
                    <list-item>
                        <p>Coping ability section, last paragraph: This section could also mention CAB-LA, as well as other PrEP products under development (e.g., lenacapavir). Moreover, remove the word &#x201c;early&#x201d; when speaking of clinical trials for DVR.</p>
                    </list-item>
                    <list-item>
                        <p>Control section, first paragraph: I think it is an overstatement to say that there is success in improving choice. While new PrEP products are becoming available, their roll-out is slow and access is limited. The choices for most people are really limited to condoms and oral PrEP.</p>
                    </list-item>
                </list> Interaction level 
                <list list-type="bullet">
                    <list-item>
                        <p>Catering to multiple needs section: This factor, as described at the beginning of this section and in the table, seems to be more about the individual rather than the interaction level. As the section goes on, it focuses more on interactions between healthcare providers and individuals, which is more suitable for this section. So the authors may want to rephrase the heading and description of this factor.</p>
                    </list-item>
                    <list-item>
                        <p>Catering to multiple needs, second paragraph: The statement on PrEP is hugely outdated (as there has been a significant scale-up of PrEP in the region since 2020). Please revise.</p>
                    </list-item>
                    <list-item>
                        <p>Interaction level: whole section heavily focuses on healthcare provider and the provision of health services (including through DSD models). While appropriate, there is limited focus on partners, families, and communities. Only in the &#x201c;Building engaged interactions&#x201d; section, there is some (limited) mentioning of partner involvement. I suggest expanding on this.</p>
                    </list-item>
                    <list-item>
                        <p>Availability of supportive stakeholders, third paragraph: The authors may want to consider examples of peer-led services from Thailand and Vietnam.</p>
                    </list-item>
                </list> Systemic level 
                <list list-type="bullet">
                    <list-item>
                        <p>Societal constraints section: More could be included on interventions that aimed to address the harmful gender norms mentioned in this section.</p>
                    </list-item>
                    <list-item>
                        <p>Economic vulnerabilities section: The authors combine in this section elements of individual economic vulnerabilities (first paragraph) and system constraints (second paragraph). These elements are quite different. The second aspect may deserve its own section (could be titled &#x201c;Health systems constraints&#x201d;).</p>
                    </list-item>
                </list> Discussion 
                <list list-type="bullet">
                    <list-item>
                        <p>Second paragraph: The authors mention cascade approaches for treatment and prevention but the included reference only relates to treatment. I suggest adding further references to the HIV prevention cascade.</p>
                    </list-item>
                    <list-item>
                        <p>The proposed integrated approach proposed by the authors is welcomed and useful, but given that it is a key contribution of their article, they may want to expand on this (a whole article is devoted to the &#x2018;static view&#x2019;, while only one paragraph relates to the &#x2018;dynamic view&#x2019;).</p>
                    </list-item>
                    <list-item>
                        <p>In the discussion or elsewhere, I think the article lacks a discussion on other articles that have been previously published and similarly discussed ecosystem models for HIV prevention (for instance, there is extensive literature on the socio-ecological model, which is very similar to the authors&#x2019; model). It is important to situate the article in the broader literature and justify its added value.</p>
                    </list-item>
                </list> Conclusion 
                <list list-type="bullet">
                    <list-item>
                        <p>I suggest avoiding the statement &#x201c;unlike treatment&#x201d; as many of the factors discussed relate to treatment as well.</p>
                    </list-item>
                    <list-item>
                        <p>The authors mention a decline in incidence and prevalence. This may be true for southern and eastern Africa, but many other regions have been experiencing stable or even increasing incidence. The authors may want to reflect on this.</p>
                    </list-item>
                </list>
            </p>
            <p>Does the article adequately reference differing views and opinions?</p>
            <p>Yes</p>
            <p>Are all factual statements correct, and are statements and arguments made adequately supported by citations?</p>
            <p>Partly</p>
            <p>Is the Open Letter written in accessible language?</p>
            <p>Yes</p>
            <p>Where applicable, are recommendations and next steps explained clearly for others to follow?</p>
            <p>Yes</p>
            <p>Is the rationale for the Open Letter provided in sufficient detail?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>HIV, global health, epidemiology</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment3752-37951">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Gantayat</surname>
                            <given-names>Nishan</given-names>
                        </name>
                        <aff>Behavioral Science, Not Applicable, Mumbai, Maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>22</day>
                    <month>11</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Thank you for the valuable feedback. Please find below our response, which has been incorporated into the new version.&#x00a0;</p>
                <p> </p>
                <p> Abstract 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the second paragraph, the authors mention that they focus on &#x201c;demand for HIV prevention&#x201d;. I think the article is more broadly about &#x201c;factors that influence uptake of prevention products&#x201d;, not just demand-side factors.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made.</italic>
                </p>
                <p> </p>
                <p> Introduction 
                    <list list-type="bullet">
                        <list-item>
                            <p>First paragraph: This article is focused on HIV prevention, so it may be more appropriate to start the article with a focus on HIV prevention target. The 95-95-95 targets are about HIV treatment. While treatment-as-prevention is an important concept, we know that there are limits to its impact on HIV incidence, so primary prevention is most critical.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made to include prevention-relevant numbers.&#x00a0;</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Second paragraph: &#x201c;CAB-LA&#x201d; is a more commonly used acronym for long-acting injectable cabotegravir. The authors should spell this out on first occurrence. Furthermore, CAB-LA should not be described as &#x201c;ART&#x201d; (although it is an antiretroviral drug). Finally, the authors may want to add information on oral PrEP and nuance the statement on new PrEP products as these are not yet widely available.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted. Edits and additions made.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Third paragraph: Similar to the comment above, the focus should not be on an HIV treatment target (90-90-90).</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made to include prevention-relevant statement.&#x00a0;</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Seventh paragraph: Since the authors note that they focus on the prevention landscape in eastern and southern Africa, they may want to include some general background on the region, such as HIV incidence and HIV prevention efforts and progress (including among key populations).</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made to include region-specific numbers.&#x00a0;</italic>
                </p>
                <p>
                    <italic> Individual level</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Table 1: &#x201c;Control&#x201d; in the last row should also be in bold.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Table 1: The statement in the &#x201c;Relevance&#x201d; section requires a reference or needs to be written in a more general sense.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Risk saliency section, third paragraph: Here, and elsewhere, avoid language around &#x201c;risky sexual behaviour&#x201d;. This language can be stigmatizing. More neutral language of &#x201c;behaviour associated with increased HIV acquisition risk&#x201d; or something similar should be adopted.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits to the whole of the document. Thank you for pointing this out.&#x00a0;</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Coping ability section: Towards the end of this section, different PrEP products are described. This should be included in the introduction of the article.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted. DVR and CAB-LA have already been mentioned in the introduction.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Coping ability section, last paragraph: This section could also mention CAB-LA, as well as other PrEP products under development (e.g., lenacapavir). Moreover, remove the word &#x201c;early&#x201d; when speaking of clinical trials for DVR.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits to remove &#x201c;early&#x201d; and also mention CAB-LA.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Control section, first paragraph: I think it is an overstatement to say that there is success in improving choice. While new PrEP products are becoming available, their roll-out is slow and access is limited. The choices for most people are really limited to condoms and oral PrEP.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made in the language.</italic>
                </p>
                <p> </p>
                <p> Interaction level 
                    <list list-type="bullet">
                        <list-item>
                            <p>Catering to multiple needs section: This factor, as described at the beginning of this section and in the table, seems to be more about the individual rather than the interaction level. As the section goes on, it focuses more on interactions between healthcare providers and individuals, which is more suitable for this section. So the authors may want to rephrase the heading and description of this factor.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Catering to multiple needs, second paragraph: The statement on PrEP is hugely outdated (as there has been a significant scale-up of PrEP in the region since 2020). Please revise.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and revision made</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Interaction level: whole section heavily focuses on healthcare provider and the provision of health services (including through DSD models). While appropriate, there is limited focus on partners, families, and communities. Only in the &#x201c;Building engaged interactions&#x201d; section, there is some (limited) mentioning of partner involvement. I suggest expanding on this.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and some edits made to expand on partner, family etc.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Availability of supportive stakeholders, third paragraph: The authors may want to consider examples of peer-led services from Thailand and Vietnam.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and citations have been added.</italic>
                </p>
                <p> </p>
                <p> Systemic level 
                    <list list-type="bullet">
                        <list-item>
                            <p>Societal constraints section: More could be included on interventions that aimed to address the harmful gender norms mentioned in this section.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and some additional norms related citations have been added.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Economic vulnerabilities section: The authors combine in this section elements of individual economic vulnerabilities (first paragraph) and system constraints (second paragraph). These elements are quite different. The second aspect may deserve its own section (could be titled &#x201c;Health systems constraints&#x201d;).</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made.</italic>
                </p>
                <p> </p>
                <p> Discussion 
                    <list list-type="bullet">
                        <list-item>
                            <p>Second paragraph: The authors mention cascade approaches for treatment and prevention but the included reference only relates to treatment. I suggest adding further references to the HIV prevention cascade.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and citations added.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>The proposed integrated approach proposed by the authors is welcomed and useful, but given that it is a key contribution of their article, they may want to expand on this (a whole article is devoted to the &#x2018;static view&#x2019;, while only one paragraph relates to the &#x2018;dynamic view&#x2019;).'</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and have tried to expand on the section.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the discussion or elsewhere, I think the article lacks a discussion on other articles that have been previously published and similarly discussed ecosystem models for HIV prevention (for instance, there is extensive literature on the socio-ecological model, which is very similar to the authors&#x2019; model). It is important to situate the article in the broader literature and justify its added value.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and have tried to situate the letter in midst of other papers on socio-ecological models&#x2019; application to HIV prevention.</italic>
                </p>
                <p> </p>
                <p> Conclusion 
                    <list list-type="bullet">
                        <list-item>
                            <p>I suggest avoiding the statement &#x201c;unlike treatment&#x201d; as many of the factors discussed relate to treatment as well.</p>
                        </list-item>
                    </list> 
                    <italic>Authors' Response - Noted and edits made.</italic> 
                    <list list-type="bullet">
                        <list-item>
                            <p>The authors mention a decline in incidence and prevalence. This may be true for southern and eastern Africa, but many other regions have been experiencing stable or even increasing incidence. The authors may want to reflect on this.</p>
                        </list-item>
                    </list> 
                    <italic>Authors Response - Noted, and edits were made so as to be more specific to the region.</italic>
                </p>
            </body>
        </sub-article>
    </sub-article>
</article>
