Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1ß has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. METHODS AND ANALYSIS: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part. The diagnostic study aims to evaluate GIFT's performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. ETHICS AND DISSEMINATION: Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d'Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484). TRIAL REGISTRATION NUMBER: NCT05723484.

Differentiated care for youth in Zimbabwe: Outcomes across the HIV care cascade.

Youth living with HIV are at higher risk than adults of disengaging from HIV care. Differentiated models of care such as community delivery of antiretroviral therapy (ART) may improve treatment outcomes. We investigated outcomes across the HIV cascade among youth accessing HIV services in a community-based setting. This study was nested in a cluster-randomised controlled trial (CHIEDZA: Clinicaltrials.gov, Registration Number: NCT03719521) conducted in three provinces in Zimbabwe and aimed to investigate the impact of a youth-friendly community-based package of HIV services, integrated with sexual and reproductive health services for youth (16-24 years), on population-level HIV viral load (VL). HIV services included HIV testing, ART initiation and continuous care, VL testing, and adherence support. Overall 377 clients were newly diagnosed with HIV at CHIEDZA, and linkage to HIV care was confirmed for 265 (70.7%, 234 accessed care at CHIEDZA and 31 with other providers); of these 250 (94.3%) started ART. Among those starting ART at CHIEDZA who did not transfer out and had enough follow up time (>6 months), 38% (68/177) were lost-to-follow-up within six months. Viral suppression (HIV Viral Load <1000 copies/ml) among those who had a test at 6 months was 90% (96/107). In addition 1162 clients previously diagnosed with HIV accessed CHIEDZA; 714 (61.4%) had a VL test, of whom 565 (79.1%) were virally suppressed. This study shows that provision of differentiated services for youth in the community is feasible. Linkage to care and retention during the initial months of ART was the main challenge and needs concerted attention to achieve the ambitious 95-95-95 UNAIDS targets.

Prevalence of hypertension and high-normal blood pressure among young adults in Zimbabwe: findings from a large, cross-sectional population-based survey.

BACKGROUND: Hypertension is the greatest driver of cardiovascular mortality and onset might be in youth. We aimed to investigate the prevalence of and risk factors for elevated blood pressure (hypertension ≥140 mm Hg systolic, ≥90 mm Hg diastolic, or both) and high-normal blood pressure (130-139 mm Hg systolic, 85-89 mm Hg diastolic, or both) among youth in Zimbabwe. METHODS: A population-based, cross-sectional survey of randomly sampled youth aged 18-24 years from 24 urban and peri-urban communities in three provinces (Harare, Bulawayo, and Mashonaland East) in Zimbabwe was conducted between Oct 4, 2021, and June 2, 2022. Standardised questionnaires were used by research assistants to collect sociodemographic, behavioural, and clinical data. Height, bodyweight, and blood pressure were recorded. Three seated blood pressure measurements were taken at standardised timepoints during participant interview using a digital sphygmomanometer and cuffs sized on mid-upper arm circumference. The association of potential risk factors with elevated blood pressure was examined using multivariable logistic regression. FINDINGS: 17 682 (94·4%) of 18 729 eligible participants were recruited, 17 637 (99·7%) of whom had complete data, and 16 883 (95·7%) of whom were included in the final study sample after excluding 754 (4·3%) pregnant women. The median age was 20 years (IQR 19-22), 9973 (59·1%) participants were female, and 6910 (40·9%) were male. The prevalence of hypertension was 7·4% (95% CI 7·0-7·8) and high-normal blood pressure was 12·2% (11·7-12·7). Overall, prevalence of hypertension was higher in men (8·7% [95% CI 8·2-9·6]) than in women (6·6% [6·0-6·9]), but with age increased to similar levels (at age 18 years 7·3% [6·2-8·6] and 4·3% [3·5-5·2]; at age 23-24 years 10·9% [9·3-12·6] and 9·5% [8·4-10·7] in men and women, respectively). After adjusting for factors associated with hypertension in the crude analysis, hypertension was associated with male sex (adjusted odds ratio 1·53 [95% CI 1·36-1·74]), increasing age (age 19-20 years 1·20 [1·00-1·44]; age 21-22 years 1·45 [1·20-1·75]; age 23-24 years 1·90 [1·57-2·30], vs age 18 years), and BMI of 30·0 kg/m2 or more (1·94 [1·53-2·47] vs 18·5-24·9 kg/m2). A BMI of 18·5 kg/m2 or less (0·79 [0·63-0·98] vs 18·5-24·9 kg/m2) and living with HIV (0·71 [0·55-0·92]) were associated with lower odds of hypertension. INTERPRETATION: Prevalence of elevated blood pressure is high among urban and peri-urban youth in Zimbabwe and increases rapidly with age. Further research is needed to understand drivers of blood pressure elevation and the extent of target organ damage in youth in Zimbabwe and similar sub-Saharan African settings, to guide implementation of prevention and management strategies. FUNDING: Wellcome Trust.

Financial incentives to improve uptake of partner services for sexually transmitted infections in Zimbabwe antenatal care: protocol for a cluster randomised trial.

Introduction: Sexually transmitted infections (STIs) such as chlamydia, gonorrhoea, trichomoniasis, and syphilis, are associated with adverse birth outcomes. Treatment should be accompanied by partner services to prevent re-infection and break cycles of transmission. Partner services include the processes of partner notification (PN) as well as arranging for their attendance for testing and/or treatment. However, due to a complex mix of cultural, socio-economic, and health access factors, uptake of partner services is often very low, in many settings globally. Alternative strategies to facilitate partner services are therefore needed.The aim of this study is to assess the impact of a small financial incentive on uptake of partner services for STIs as part of antenatal care (ANC) services in Zimbabwe. Methods and analysis: This trial will be embedded within a prospective interventional study in Harare, aiming to evaluate integration of point-of-care diagnostics for STIs into ANC settings. One thousand pregnant women will be screened for chlamydia, gonorrhoea, trichomoniasis, and syphilis. All individuals with STIs will be offered treatment, risk reduction counselling, and client PN. Each clinic day will be randomised 1:1 to be an incentive or non-incentive day. On incentive days, participants diagnosed with a curable STI will be offered a PN slip, that when returned will entitle their partners to $3 (USD) in compensation. On non-incentive days, regular PN slips with no incentive are provided.The primary outcome measure is the proportion of individuals with at least one partner who returns for partner services based on administrative records. Secondary outcomes will include the number of days between index case diagnosis and the partner attending for partner services, uptake of PN slips by pregnant women, adverse birth outcomes in index cases, partners who receive treatment, and intervention cost. Registration: Pan African Clinical Trials Registry: PACTR202302702036850 (Approval date 18 th February 2022).

Fertility preservation and protection: young women's decision-making about contraceptive use in Zimbabwe.

The study explored social and health system influences on young women's decision-making about family planning in a community setting with low uptake. Seventy-two semi-structured interviews were conducted between April 2020 and November 2021, with both young women accessing, and healthcare workers providing, a community-based integrated package of HIV and sexual and reproductive health services (CHIEDZA) in Zimbabwe. Data were thematically analysed. Although long-acting contraception was freely available as part of the CHIEDZA initiative, uptake was low. Young women's contraception choices were influenced by a desired reproductive sequence, which reflected prevailing social norms and was conveyed by peers and female relatives. Nulliparous young women preferred short-term contraception and avoided hormonal contraceptives prepartum to 'preserve' their fertility. Once fertility had been confirmed within marriage through the birth of a child, hormonal contraceptive use became socially permissible. Healthcare workers, cognisant of community discourse, sensitively proposed alternative approaches. Increasing the availability of correct and adequate information and commodities is critical to improving the uptake of contraceptives for young women, but it is insufficient alone. Recognising and responding to local contextual understandings which frame considerations of appropriateness is paramount. Successful implementation of family planning interventions requires engaging with social norms and the influential groups that perpetuate them.

Addressing sociodemographic disparities in COVID-19 vaccine uptake among youth in Zimbabwe.

INTRODUCTION: COVID-19 vaccine acceptance research has mostly originated from high-income countries and reasons why youth may not get vaccinated may differ in low-income settings. Understanding vaccination coverage across different population groups and the sociocultural influences in healthcare delivery is important to inform targeted vaccination campaigns. METHODS: A population-based survey was conducted in 24 communities across three provinces (Harare, Bulawayo and Mashonaland East) in Zimbabwe between October 2021 and June 2022. Youth aged 18-24 years were randomly selected using multistage sampling. Sociodemographic characteristics, COVID-19 vaccination uptake and reasons for non-uptake were collected, and odds of vaccination was investigated using logistic regression. RESULTS: 17 682 youth were recruited in the survey (n=10 742, 60.8% female). The median age of participants was 20 (IQR: 19-22) years. Almost two thirds (n=10 652, 60.2%) reported receiving at least one dose of COVID-19 vaccine. A higher proportion of men than women had been vaccinated (68.9% vs 54.7%), and vaccination prevalence increased with age (<19 years: 57.5%, 20-22: 61.5%, >23: 62.2%). Lack of time to get vaccinated, belief that the vaccine was unsafe and anxiety about side effects (particularly infertility) were the main reasons for not getting vaccinated. Factors associated with vaccination were male sex (OR=1.69, 95% CI 1.58 to 1.80), increasing age (>22 years: OR=1.12, 95% CI 1.04 to 1.21), education level (postsecondary: OR=4.34, 95% CI 3.27 to 5.76) and socioeconomic status (least poor: OR=1.32, 95% CI 1.20 to 1.47). CONCLUSION: This study found vaccine inequity across age, sex, educational attainment and socioeconomic status among youth. Strategies should address these inequities by understanding concerns and tailoring vaccine campaigns to specific groups.

Delivery of index-linked HIV testing for children: learnings from a qualitative process evaluation of the B-GAP study in Zimbabwe.

BACKGROUND: Index-linked HIV testing for children, whereby HIV testing is offered to children of individuals living with HIV, has the potential to identify children living with undiagnosed HIV. The "Bridging the Gap in HIV Testing and Care for Children in Zimbabwe" (B-GAP) study implemented and evaluated the provision of index-linked HIV testing for children aged 2-18 years in Zimbabwe. We conducted a process evaluation to understand the considerations for programmatic delivery and scale-up of this strategy. METHODS: We used implementation documentation to explore experiences of the field teams and project manager who delivered the index-linked testing program, and to describe barriers and facilitators to index-linked testing from their perspectives. Qualitative data were drawn from weekly logs maintained by the field teams, monthly project meeting minutes, the project coordinator's incident reports and WhatsApp group chats between the study team and the coordinator. Data from each of the sources was analysed thematically and synthesised to inform the scale-up of this intervention. RESULTS: Five main themes were identified related to the implementation of the intervention: (1) there was reduced clinic attendance of potentially eligible indexes due to community-based differentiated HIV care delivery and collection of HIV treatment by proxy individuals; (2) some indexes reported that they did not live in the same household as their children, reflecting the high levels of community mobility; (3) there were also thought to be some instances of 'soft refusal'; (4) further, delivery of HIV testing was limited by difficulties faced by indexes in attending health facilities with their children for clinic-based testing, stigma around community-based testing, and the lack of familiarity of indexes with caregiver provided oral HIV testing; (5) and finally, test kit stockouts and inadequate staffing also constrained delivery of index-linked HIV testing. CONCLUSIONS: There was attrition along the index-linked HIV testing cascade of children. While challenges remain at all levels of implementation, programmatic adaptations of index-linked HIV testing approaches to suit patterns of clinic attendance and household structures may strengthen implementation of this strategy. Our findings highlight the need to tailor index-linked HIV testing to subpopulations and contexts to maximise its effectiveness.

Investigating point-of-care diagnostics for sexually transmitted infections and antimicrobial resistance in antenatal care in Zimbabwe (IPSAZ): protocol for a mixed-methods study.

INTRODUCTION: Sexually transmitted infections (STIs) can cause serious morbidity, including pelvic inflammatory disease, and adverse pregnancy outcomes. In low/middle-income countries, limited laboratory infrastructure has resulted in a syndrome-based approach being used for management of STIs, which has poor sensitivity and specificity, leading to considerable underdiagnosis and overtreatment. The WHO has called for development and evaluation of strategies to inform replacement of syndromic management by diagnostic testing.The aim of this project is to evaluate a strategy of point-of-care testing for six STIs in antenatal care (ANC) in Zimbabwe. METHODS AND ANALYSIS: A prospective interventional study will be conducted in ANC clinics in Harare province, Zimbabwe. One thousand pregnant women will be recruited when registering for routine ANC. Alongside routine HIV and syphilis testing, participants will be offered an integrated screening package including testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and hepatitis B. All individuals with STIs will receive treatment, partner notification services, risk reduction counselling and referral if needed according to national guidelines. Gonorrhoea samples will be cultured and tested for antimicrobial resistance as per WHO enhanced gonococcal antimicrobial surveillance programme guidelines.The primary outcome measure is the composite prevalence of CT, NG, TV, syphilis and hepatitis B. A mixed-methods process evaluation and economic evaluation will be conducted to understand the acceptability, feasibility and cost-effectiveness of integrated STI testing, compared with standard of care (syndromic management). ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board, and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policymaking bodies. TRIAL REGISTRATION NUMBER: NCT05541081.

A mixed-methods study measuring the effectiveness of a menstrual health intervention on menstrual health knowledge, perceptions and practices among young women in Zimbabwe.

OBJECTIVES: While integral to women's physical and mental well-being, achieving good menstrual health (MH) remains a challenge for many women. This study investigated the effectiveness of a comprehensive MH intervention on menstrual knowledge, perceptions and practices among women aged 16-24 years in Harare, Zimbabwe. DESIGN: A mixed-methods prospective cohort study with pre-post evaluation of an MH intervention. SETTING: Two intervention clusters in Harare, Zimbabwe. PARTICIPANTS: Overall, 303 female participants were recruited, of whom 189 (62.4%) were seen at midline (median follow-up 7.0; IQR 5.8-7.7 months) and 184 (60.7%) were seen at endline (median follow-up 12.4; IQR 11.9-13.8 months). Cohort follow-up was greatly affected by COVID-19 pandemic and associated restrictions. INTERVENTION: The MH intervention provided MH education and support, analgesics, and a choice of menstrual products in a community-based setting to improve MH outcomes among young women in Zimbabwe. PRIMARY AND SECONDARY OUTCOMES: Effectiveness of a comprehensive MH intervention on improving MH knowledge, perceptions, and practices among young women over time. Quantitative questionnaire data were collected at baseline, midline, and endline. At endline, thematic analysis of four focus group discussions was used to further explore participants' menstrual product use and experiences of the intervention. RESULTS: At midline, more participants had correct/positive responses for MH knowledge (adjusted OR (aOR)=12.14; 95% CI: 6.8 to 21.8), perceptions (aOR=2.85; 95% CI: 1.6 to 5.1) and practices for reusable pads (aOR=4.68; 95% CI: 2.3 to 9.6) than at baseline. Results were similar comparing endline with baseline for all MH outcomes. Qualitative findings showed that sociocultural norms, stigma and taboos around menstruation, and environmental factors such as limited access to water, sanitation and hygiene facilities affected the effect of the intervention on MH outcomes. CONCLUSIONS: The intervention improved MH knowledge, perceptions and practices among young women in Zimbabwe, and the comprehensive nature of the intervention was key to this. MH interventions should address interpersonal, environmental and societal factors. TRIAL REGISTRATION NUMBER: NCT03719521.

Family Planning Experiences and Needs of Young Women Living With and Without HIV Accessing an Integrated HIV and SRH Intervention in Zimbabwe-An Exploratory Qualitative Study.

Background: People living with HIV have higher unmet family planning needs compared to those without HIV. This is heightened for young people. However, the provision of family planning for young people within HIV programmes is uncommon. We investigated family planning uptake, acceptability of, and engagement with a service offering integrated HIV and sexual and reproductive health services for youth in a community-based setting in Zimbabwe. Methods: CHIEDZA, a community-based intervention offering integrated HIV and sexual and reproductive health services to young people aged 16-24 years, is being trialed in Zimbabwe. This exploratory qualitative study was nested within an ongoing study process evaluation. Data was collected between March-May 2021 with two sets of interviews conducted: I) twelve semi-structured interviews with young women living with HIV aged 17-25 years and II) fifteen interviews conducted with young women without HIV aged between 20 and 25 years who used a contraceptive method. A thematic analysis approach was used. Results: Before engaging with CHIEDZA, young women had experienced judgmental providers, on account of their age, and received misinformation about contraceptive use and inadequate information about ART-contraceptive interactions. These presented as barriers to uptake and engagement. Upon attending CHIEDZA, all the young women reported receiving non-judgmental care. For those living with HIV, they were able to access integrated HIV and family planning services that supported them having broader sexual and reproductive needs beyond their HIV diagnosis. The family planning preference of young women living with HIV included medium to long-acting contraceptives to minimize adherence challenges, and desired partner involvement in dual protection to prevent HIV transmission. CHIEDZA's ability to meet these preferences shaped uptake, acceptability, and engagement with integrated HIV and family services. Conclusions: Recommendations for an HIV and family planning integrated service for young people living with HIV include: offering a range of services (including method-mix contraceptives) to choose from; supporting their agency to engage with the services which are most acceptable to them; and providing trained, supportive, knowledgeable, and non-judgmental health providers who can provide accurate information and counsel. We recommend youth-friendly, differentiated, person-centered care that recognize the multiple and intersecting needs of young people living with HIV.

Interrupted Access to and Use of Family Planning Among Youth in a Community-Based Service in Zimbabwe During the First Year of the COVID-19 Pandemic.

The COVID-19 pandemic has had serious impacts on economic, social, and health systems, and fragile public health systems have become overburdened in many countries, exacerbating existing service delivery challenges. This study describes the impact of the COVID-19 pandemic on family planning services within a community-based integrated HIV and sexual and reproductive health intervention for youth aged 16-24 years being trialled in Zimbabwe (CHIEDZA). It examines the experiences of health providers and clients in relation to how the first year of the pandemic affected access to and use of contraceptives.

"Other risks don't stop": adapting a youth sexual and reproductive health intervention in Zimbabwe during COVID-19.

COVID-19 threatens hard-won gains in sexual and reproductive health (SRH) through compromising the ability of services to meet needs. Youth are particularly threatened due to existing barriers to their access to services. CHIEDZA is a community-based integrated SRH intervention for youth being trialled in Zimbabwe. CHIEDZA closed in March 2020, in response to national lockdown, and reopened in May 2020, categorised as an essential service. We aimed to understand the impact of CHIEDZA's closure and its reopening, with adaptations to reduce COVID-19 transmission, on provider and youth experiences. Qualitative methods included interviews with service providers (n = 22) and youth (n = 26), and observations of CHIEDZA sites (n = 10) and intervention team meetings (n = 7). Analysis was iterative and inductive. The sudden closure of CHIEDZA impeded youth access to SRH services. The reopening of CHIEDZA was welcomed, but the necessary adaptations impacted the intervention and engagement with it. Adaptations restricted time with healthcare providers, heightening the tension between numbers of youths accessing the service and quality of service provision. The removal of social activities, which had particularly appealed to young men, impacted youth engagement and access to services, particularly for males. This paper demonstrates how a community-based youth-centred SRH intervention has been affected by and adapted to COVID-19. We demonstrate how critical ongoing service provision is, but how adaptations negatively impact service provision and youth engagement. The impact of adaptations additionally emphasises how time with non-judgemental providers, social activities, and integrated services are core components of youth-friendly services, not added extras.

"It was difficult to offer same day results": evaluation of community-based point-of-care testing for sexually transmitted infections among youth using the GeneXpert platform in Zimbabwe.

BACKGROUND: Point-of-care testing for sexually transmitted infections (STIs) may improve diagnosis and treatment of STIs in low- and middle-income counties. We explored the facilitators and barriers to point-of-care testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) for youth in community-based settings in Zimbabwe. METHODS: This study was nested within a cluster randomised trial of community-based delivery of integrated HIV and sexual and reproductive health services for youth aged 16 to 24 years. On-site CT/NG testing on urine samples using the Xpert® CT/NG test was piloted in four intervention clusters, with testing performed by service providers. On-site testing was defined as sample processing on the same day and site as sample collection. Outcomes included proportion of tests processed on-site, time between sample collection and collection of results, and proportion of clients receiving treatment. In-depth interviews were conducted with nine service providers and three staff members providing study co-ordination or laboratory support to explore facilitators and barriers to providing on-site CT/NG testing. RESULTS: Of 847 Xpert tests, 296 (35.0%) were performed on-site. Of these, 61 (20.6%) were positive for CT/NG; one (1.6%) received same day aetiological treatment; 33 (54.1%) presented later for treatment; and 5 (8.2%) were treated as a part of syndromic management. There was no difference in the proportion of clients who were treated whether their sample was processed on or off-site (64% (39/61) vs 60% (66/110); p = 0.61). The median (IQR) number of days between sample collection and collection of positive results was 14 (7-35) and 14 (7-52.5) for samples processed on and off-site, respectively, The interviews revealed four themes related to the provision of on-site testing associated with the i) diagnostic device ii) environment, iii) provider, and iv) clients. Some of the specific barriers identified included insufficient testing capacity, inadequate space, as well as reluctance of clients to wait for their results. CONCLUSIONS: In addition to research to optimise the implementation of point-of-care tests for STIs in resource-limited settings, the development of new platforms to reduce analytic time will be necessary to scale up STI testing and reduce the attrition between testing and treatment. TRIAL REGISTRATION: Registered in clinical trials.gov ( NCT03719521 ).

Adolescent Health Series: Engagement with young people as partners in health research: Four case studies from Sub-Saharan Africa.

OBJECTIVES: Existing health services for young people (YP)(10-24 years), which are predominantly designed for but not with young people, often do not meet YP's needs. The 2018 Global Consensus Statement on meaningful adolescent and youth engagement affirms that YP have a fundamental right to actively and meaningfully engage in all matters that affect their lives. We present four case studies from three countries in sub-Saharan Africa as practical examples of the engagement of young people as partners in health research. We critically reflect on best practices to inform and guide the increasing adoption of collaborative approaches. METHODS: We developed a narrative summary of each case study through review of study documentation and discussions with research staff and young people. A youth engagement framework was used to describe partnership activities according to the following dimensions: purpose, process, positioning, perspective, power relations, place and protection. We reflected on innovative practices used, overall level of participation achieved and strategies to address ethical, logistical and/or financial barriers. RESULTS: In all case studies, we found evidence of engagement activities that aligned with the Global Consensus Statement on Meaningful Youth Engagement. However, access to participation was often uneven and despite efforts, marginalised young people continue to have insufficient opportunities to engage. Furthermore, although young people had some opportunity to influence the research methods, many of the key design decisions had been determined prior to their involvement. In our case studies, researchers had built in insufficient opportunities to evaluate the level and impact of youth engagement. CONCLUSIONS: We therefore recommend early involvement of young people in the research process so that they can contribute to setting the research agenda, the design of planned studies and thus increase the scope of their engagement from the beginning. Youth engagement activities need to be evaluated from the perspective of all stakeholders including young people themselves with a focus on opportunities to engage, the level of engagement achieved and impact of engagement. From the beginning, researchers should provide space for learning, and involve young people in encouraging critical reflection of what does not yet work, as well as what does, to enable improvements.

The impact of community-based integrated HIV and sexual and reproductive health services for youth on population-level HIV viral load and sexually transmitted infections in Zimbabwe: protocol for the CHIEDZA cluster-randomised trial.

Background: Youth have poorer HIV-related outcomes when compared to other age-groups. We describe the protocol for a cluster randomised trial (CRT) to evaluate the effectiveness of community-based, integrated HIV and sexual and reproductive health services for youth on HIV outcomes. Protocol: The CHIEDZA trial is being conducted in three provinces in Zimbabwe, each with eight geographically demarcated areas (clusters) (total 24 clusters) randomised 1:1 to standard of care (existing health services) or to the intervention. The intervention comprises community-based delivery of HIV services including testing, antiretroviral therapy, treatment monitoring and adherence support as well as family planning, syndromic management of sexually transmitted infections (STIs), menstrual health management, condoms and HIV prevention and general health counselling. Youth aged 16-24 years living within intervention clusters are eligible to access CHIEDZA services. A CRT of STI screening (chlamydia, gonorrhoea and trichomoniasis) is nested in two provinces (16 of 24 clusters). The intervention is delivered over a 30-month period by a multidisciplinary team trained and configured to provide high-quality, youth friendly services.Outcomes will be ascertained through a population-based survey of 18-24-year-olds. The primary outcome is HIV viral load <1000 copies/ml in those living with HIV and proportion who test positive for STIs (for the nested trial). A detailed process and cost evaluation of the trial will be conducted. Ethics and Dissemination: The trial protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policy-making bodies. Trial Registration: https://clinicaltrials.gov/: NCT03719521.

Putting youth at the centre: co-design of a community-based intervention to improve HIV outcomes among youth in Zimbabwe.

Background:  Youth have disproportionately poor HIV outcomes. We aimed to co-design a community-based intervention with youth to improve HIV outcomes among 16-24 year-olds, to be trialled in Zimbabwe. Methods:  We conducted 90 in-depth interviews with youth, family members, community gatekeepers and healthcare providers to understand the barriers to uptake of existing HIV services. The interviews informed an outline intervention, which was refined through two participatory workshops with youth, and subsequent pilot-testing. Results:  Participants considered existing services inaccessible and unappealing: health facilities were perceived to be for 'sick people', centred around HIV and served by judgemental providers. Proposed features of an intervention to overcome these barriers included: i) delivery in a youth-only community space; ii) integration of HIV services with broader health services; iii) non-judgemental skilled healthcare providers; iv) entertainment to encourage attendance; and v) tailored timings and outreach. The intervention framework stands on three core pillars, based on optimizing access (community-based youth-friendly settings); uptake and acceptability (service branding, confidentiality, and social activities); and content and quality (integrated HIV care cascade, high quality products, and trained providers). Conclusions:  Ongoing meaningful youth engagement is critical to designing HIV interventions if access, uptake, and coverage is to be achieved.

Identifying youth at high risk for sexually transmitted infections in community-based settings using a risk prediction tool: a validation study.

BACKGROUND : Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common bacterial sexually transmitted infections (STIs) worldwide. In the absence of affordable point-of-care STI tests, WHO recommends STI testing based on risk factors. This study aimed to develop a prediction tool with a sensitivity of > 90% and efficiency (defined as the percentage of individuals that are eligible for diagnostic testing) of < 60%. METHODS: This study offered CT/NG testing as part of a cluster-randomised trial of community-based delivery of sexual and reproductive health services to youth aged 16-24 years in Zimbabwe. All individuals accepting STI testing completed an STI risk factor questionnaire. The outcome was positivity for either CT or NG. Backwards-stepwise logistic regression was performed with p ≥ 0.05 as criteria for exclusion. Coefficients of variables included in the final multivariable model were multiplied by 10 to generate weights for a STI risk prediction tool. A maximum likelihood Receiver Operating Characteristics (ROC) model was fitted, with the continuous variable score divided into 15 categories of equal size. Sensitivity, efficiency and number needed to screen were calculated for different cut-points. RESULTS: From 3 December 2019 to 5 February 2020, 1007 individuals opted for STI testing, of whom 1003 (99.6%) completed the questionnaire. CT/NG prevalence was 17.5% (95% CI 15.1, 19.8) (n = 175). CT/NG positivity was independently associated with being female, number of lifetime sexual partners, relationship status, HIV status, self-assessed STI risk and past or current pregnancy. The STI risk prediction score including those variables ranged from 2 to 46 with an area under the ROC curve of 0.72 (95% CI 0.68, 0.76). Two cut-points were chosen: (i) 23 for optimised sensitivity (75.9%) and specificity (59.3%) and (ii) 19 to maximise sensitivity (82.4%) while keeping efficiency at < 60% (59.4%). CONCLUSIONS: The high prevalence of STIs among youth, even in those with no or one reported risk factor, may preclude the use of risk prediction tools for selective STI testing. At a cut-point of 19 one in six young people with STIs would be missed.

A costing analysis of B-GAP: index-linked HIV testing for children and adolescents in Zimbabwe.

BACKGROUND: By testing children and adolescents of HIV positive caretakers, index-linked HIV testing, a targeted HIV testing strategy, has the ability to identify high risk children and adolescents earlier and more efficiently, compared to blanket testing. We evaluated the incremental cost of integrating index-linked HIV testing via three modalities into HIV services in Zimbabwe. METHODS: A mixture of bottom-up and top-down costing was employed to estimate the provider cost per test and per HIV diagnosis for 2-18 year olds, through standard of care testing, and the incremental cost of index-linked HIV testing via three modalities: facility-based testing, home-based testing by a healthcare worker, and testing at home by the caregiver using an oral mucosal transudate test. In addition to interviews, direct observation and study process data, facility registries were abstracted to extract outcome data and resource use. Costs were converted to 2019 constant US$. RESULTS: The average cost per standard of care test in urban facilities was US$5.91 and US$7.15 at the rural facility. Incremental cost of an index-linked HIV test was driven by the uptake and number of participants tested. The lowest cost approach in the urban setting was home-based testing (US$6.69) and facility-based testing at the rural clinic (US$5.36). Testing by caregivers was almost always the most expensive option (rural US$62.49, urban US$17.49). CONCLUSIONS: This is the first costing analysis of index-linked HIV testing strategies. Unit costs varied across sites and with uptake. When scaling up, alternative testing solutions that increase efficiency such as index-linked HIV testing of the entire household, as opposed to solely targeting children/adolescents, need to be explored.

Feasibility and Accuracy of HIV Testing of Children by Caregivers Using Oral Mucosal Transudate HIV Tests.

BACKGROUND: Children encounter multiple barriers in accessing facilities. HIV self-testing using oral mucosal transudate (OMT) tests has been shown to be effective in reaching hard-to-reach populations. We evaluated the feasibility and accuracy of caregivers conducting HIV testing using OMTs in children in Zimbabwe. METHODS: We offered OMTs to caregivers (>18 years) living with HIV to test children (2-18 years) living in their households. All caregivers were provided with manufacturer instructions. In Phase 1 (January-December 2018, 9 clinics), caregivers additionally received a demonstration by a provider using a test kit and video. In Phase 2 (January-May 2019, 3 clinics), caregivers did not receive a demonstration. We collected demographic data and assessed caregiver's ability to perform the test and interpret results. Caregiver performance was assessed by direct observation and scored using a predefined checklist. Factors associated with obtaining a full score were analyzed using logistic regression. RESULTS: Overall 400 caregivers (83.0% female, median age 38 years) who were observed tested 786 children (54.6% female, median age 8 years). For most tests, caregivers correctly collected oral fluid [87.1% without provider demonstrations (n = 629) and 96.8% with demonstrations (n = 157), P = 0.002]. The majority correctly used a timer (90.3% without demonstrations and 96.8% with demonstrations, P = 0.02). In multivariate logistic regression caregivers who obtained a full score for performance were more likely to have received a demonstration (odds ratio 4.14, 95% confidence interval: 2.01 to 8.50). CONCLUSIONS: Caregiver-provided testing using OMTs is a feasible and accurate HIV testing strategy for children. We recommend operational research to support implementation at scale.