{"paper_id":"16632c41-a562-42d3-bd37-b7946dd3cfa7","body_text":"HIV PrEP programmes as a framework for\ndiagnosing and treating HBV infection in adolescents\nand young adults in KwaZulu-Natal, South Africa\nGloria Sukali 1,2,3, Jacob Busang 1, Jaco Dreyer 1, Thandeka Khoza 1, Marion Delphin 3,\nNonhlanhla Okesola 1, Carina Herbst 1, Elizabeth Waddilove 3, Janine Upton 1,\nJanet Seeley 1, Collins Iwuji 1,4, Motswedi Anderson 1,3,\nPhilippa C Matthews 2,3,5*, Maryam Shahmanesh 1,5*\n* joint senior/corresponding\n1 Africa Health Research Institute, KwaZulu-Natal, South Africa\n2 Division of Infection and Immunity, University College London, Gower Street, London, WC1E\n6BT , UK\n3 The Francis Crick Institute, 1 Midland Road, London, NW1 1AT , UK\n4 Department of Global Health & Infection, Brighton and Sussex Medical School, University of\nSussex, Falmer, Brighton, BN1 9PX, UK\n5 Department of Infectious Diseases, University College London Hospital, Euston Road, London\nNW1 2BU, UK\nKey words: HIV, HBV, hepatitis B, South Africa, infection, prevention, prevalence, diagnosis,\ndecentralisation, treatment, PrEP\n1\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.\n\nAbstract\nBackground: Hepatitis B virus (HBV) is a neglected public health threat with poor community\nawareness and access to prevention, despite having a safe and effective vaccine. There are still\ngaps in diagnosis and treatment, particularly in the World Health Organization (WHO) African\nregion. New WHO HBV guidelines, for the first time, include the use of dual therapy for HBV\ntreatment (T enofovir (TDF) and Emtricitabine or Lamivudine (XTC) due to challenges in\naccessing TDF monotherapy. TDF/XTC is also recommended as Pre-Exposure Prophylaxis\n(PrEP) in adolescents and adults at risk of Human Immunodeficiency Virus (HIV).HBV\nScreening, treatment and prevention need to be decentralized to improve access. We\nhypothesize that HBV programmes in African settings can use pre-existing HIV infrastructure, in\nparticular building on PrEP programmes, for access to TDF .\nMethods: At the Africa Health Research Institute (AHRI) in KwaZulu Natal, South Africa, the\nnew Evaluation of Vukuzazi LiVEr disease - Hepatitis B (‘EVOLVE-HBV’, UCL ethics ref.\n23221/001) research programme explored the PrEP uptake and retention cascade amongst\nadolescents and youth aged 15-30 year-olds living with HBV through decentralized sexual\nhealth /HIV services of the ‘Thetha nami ngithethe nawe’ and the Long-acting HIV Pre-Exposure\nProphylaxis (LAPIS) study (UKZN BREC ethics ref. 473/2019 and 3735/2021). Following point\nof care testing (POCT) for HBsAg, follow-up venous samples were taken for laboratory\nconfirmation.\nResults: Over the time reviewed (May 2021 - Sept 2024), 15,847 adolescents and young adults\nreceived a ‘needs assessment’ by peer navigators in the community, of whom 3481 (21.9%)\nwere eligible for HIV prevention interventions and referred for clinical review. 3431 (98.6%)\naccepted HBV POCT as part of routine screening, of whom 21 (0.6%) tested positive for HBsAg.\nThese 21 individuals had not previously been aware of their HBV status, but one was already on\nantiretroviral (ART) for HIV infection. Amongst the remaining 20, 16 were considered eligible for\nPrEP , 1/16 (6.3%) decided not to take it and 15 (93.8%) started PrEP as a combined\nintervention for HBV treatment and HIV prophylaxis. When investigating follow up and retention\nin care, out of the 14/15 (93.3%) that were due for a refill, 8/14 (57,1%) returned for at least 1\nrefill, amongst whom 6/12 (50%) had two or more refills (Suppl figure 1).\nConclusion: Sexual health and PrEP programmes provide an important opportunity for HBV\ntesting and treatment for young adults across high HIV burden settings. However, attrition from\nthe care cascade at each step highlights the pressing need for interventions that address\nbarriers to sustainable delivery of long-term care. Our HBV and PrEP programmes continue\nworking to support education, clinical evaluation and service development for HBV in these\npopulations.\n2\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nIntroduction\nHigh profile global goals have been established for the elimination of hepatitis B virus (HBV) as\na public health threat, with specific targets for the year 2030 [1]. Nucleos/tide analogue (NAs)\nagents are offered to those deemed at the highest risk of chronic liver disease to reduce\nmorbidity and mortality, and to reduce transmission. T enofovir disoproxil fumarate (TDF), the\nfirst line agent, is included in the WHO essential medications list, and should be widely\naccessible and affordable (global benchmark price US $2.40/month) [2]. However, the practical\nreality is that TDF is not available or incurs high out-of-pocket costs for many high-prevalence\npopulations, including the World Health Organisation (WHO) African region, which now\naccounts for >60% of new HBV infections [2].\nIn March 2024, the WHO published new guidelines for HBV [3], which simplify and widen\ntreatment eligibility criteria, and for the first time endorse dual therapy when TDF monotherapy\nis not available. This provides flexibility for TDF to be prescribed as part of fixed-dose\ncombination therapy, together with either lamivudine (3TC) or emtricitabine (FTC), collectively\ntermed ‘TDF/XTC’ [3]. In many settings, TDF/XTC is more affordable and accessible than TDF\nmonotherapy as a result of its widespread procurement for HIV treatment. These fixed-dose\ncombinations are also used as Pre-Exposure Prophylaxis (PrEP) in adolescents/adults who are\nat risk of HIV acquisition. PrEP therefore offers the combined benefit of HBV treatment and HIV\nprevention [4]. Such approaches may be of particular strength in many African settings, where\nHBV programmes can build on expertise, infrastructure and resources that have been\ndeveloped for tackling HIV [5].\nIn South Africa (SA), HIV and HBV infection are co-endemic [6, 7]. HIV has been tackled\nthrough scale-up of education, screening and treatment, leading to proactive community\nengagement and robust access pathways to diagnosis and treatment. Antiretroviral therapy\n(ART) is free of charge through the Global Fund and the United States President’s Emergency\nPlan for AIDS Relief. In comparison, HBV infection has been neglected [8, 9], with poor\nawareness, high stigma, and low access to interventions for prevention, diagnosis and\ntreatment [10–12].\nWe here describe the results of a collaboration between translational research studies for\nprovision of HIV-PrEP and HBV care pathways, based at the Africa Health Research Institute\n(AHRI) in KwaZulu-Natal (KZN), SA. We set out to gather preliminary data to explore the\nprevalence of HBV infection among adolescents and young adults (AYA) engaging with sexual\nhealth screening and PrEP services, and to determine the uptake of PrEP (for people testing\nHBsAg-positive).\nMethods\nStudy setting and research cohorts\nWe developed a collaboration between programmes at AHRI (Figure 1). The ‘EVOLVE-HBV’\nstudy started in 2023 as a collaboration between AHRI and University College London (UCL)\nand the Francis Crick Institute in the UK, to describe HBV epidemiology in the KZN population,\ncharacterize the clinical and laboratory features of HBV infection, and engage with local\n3\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\ncommunities and healthcare providers to implement sustainable care pathways to diagnosis [10,\n13]. This study is approved by the University of KwaZulu-Natal (UKZN) Biomedical Research\nEthics Committee (BREC) (ref. 00004495/2022) in SA, and UCL ethics committee in the UK (ref.\n23221/001 EVOLVE-HBV).\nT o explore the role and impact of programmes providing HIV PrEP for tackling HBV infection in\nAYA aged 15-30 years, we used a framework established by ‘Thetha nami ngithethe nawe’\n(‘T alk to me and I’ll talk to you’ in IsiZulu) [14], which is a cluster-randomised study established\nto investigate the effectiveness, implementation and cost effectiveness of peer-led social\nmobilisation through decentralised HIV and sexual reproductive health (SRH) services,\napproved by UKZN BREC (ref. 473/2019). Young people in the community are engaged by peer\nnavigators, and offered a needs assessment. Those at risk of sexually transmitted infection\n(STI) are referred for review in nurse-led mobile clinics that provide testing and treatment, offer\ncontraception, preconception care, and tailored HIV prevention. PrEP is offered as a continuous\n(rather than event-based) intervention to those who are sexually active, and willing to engage\nwith taking daily medication and attending follow-up. Thetha nami has also provided a platform\nfor the long-acting HIV PrEP (LAPIS) study, approved by UKZN BREC (ref. 3735/2021). LAPIS\nis a cluster-randomised controlled trial of effectiveness and implementation of offering injectable\nPrEP , continuous oral daily PrEP , vaginal rings, or packs of post exposure prophylaxis.\nClinical screening, and data collection\nWe retrospectively reviewed records of participants in SRH programmes between June 2022 -\nSeptember 2024. Mobile study clinics follow a monthly schedule visiting different sites in the\nstudy area. Individuals who attend are offered HIV counselling and point of care testing (POCT),\nwith immediate information and initiation of ART for those testing HIV positive. Individuals who\nare HIV negative undergo assessment for PrEP eligibility according to SA National PrEP/ART\nguidelines (box 1). The current preferred PrEP regimen in SA is a fixed-dose combination of\noral TDF/FTC.\nAll individuals presenting at the clinics are also offered testing for STI with POCT for syphilis,\nand self-taken vaginal swabs or urine tests for gonorrhoea and chlamydia (Supplementary\nmethods). If any of the STIs are positive these individuals receive treatment [15] and the\nprogram supports partner notification.\nHepatitis B screening is undertaken using POCT in Thetha nami and taking venous blood for\nlaboratory testing in LAPIS. Confirmation tests are conducted using Abbott Architect System\n(Abbott Park, Illinois, USA). HBV vaccine is offered to those who screen HBV negative.\nSexual health screening and follow-up\nFor individuals who screened positive for HBsAg, we reviewed their progress using the care\ncascade for HBV (Figure 2), focusing on testing (offer and uptake), referral to study physician,\nPrEP uptake and return for refill. Once participants have been initiated for PrEP , they are\nscheduled for a mobile clinic appointment one month after PrEP initiation. As per national\n4\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nguidelines, refills and monitoring are every 3 months thereafter through mobile clinic\nappointments [14]; we provide community refills aiming for continuous PrEP supplies. For those\nwho do not return for a PrEP refill, the clinical and study teams aim to make contact by phone,\npeers or trackers (providing home visits).\nPrEP initiation and follow-up time definitions\n● Time 0 - initiation visit (30 day PrEP supplied)\n● Time 1 - First refill (90 days PrEP supplied)\n● Time 2 - Second PrEP refill (90 days PrEP supplied)\nResults\nCommunity screening for HBV\nOver the time period reviewed (May 2021 - Sept 2024), 15,847 AYA received a ‘needs\nassessment’ by peer navigators in the community, of whom 3481 (21.9%) were eligible for HIV\nprevention interventions and referred for clinical review. Of these, 3431 (98.6%) accepted HBV\nscreening and 21 (0.6%) tested positive for HBsAg (Table 1). Overall, most of the participants\nwere female (2019/3431, 59%) living in rural areas (2712/3431, 79%) and aged 20–24 years\n(1295/3431, 38%).\nCharacteristics of individuals living with HBV\nCompared to the HBV-negative population, the 21 AYA testing HBsAg positive were comparable\nin sex (14/21, 66.7% female), and location (13/21, 61.9% rural). However, those testing\nHBsAg-positive were typically older than their HBsAg-negative counterparts, between 25-30\nyears (18/21, 85.7%), p<0.001. The proportion of common curable STIs in AYA living with HBV\nwas no different from those who tested HBsAg-negative (7/21 vs 668/2293, 33.3% vs 29.1%\np=0.7). The proportion of syphilis in HBsAg positive was no different when compared to that of\nthe general population (1/21 vs 55/3409, 4.8 vs 1.6% p=0.3) (Suppl Table 1).\nAssessment for PrEP\nThe 21 individuals diagnosed with HBV had not previously been aware of their HBV status, but\none was already receiving ART for HIV infection. The other 20 were counselled regarding\nstarting oral PrEP , among whom 4/20 (20%) were not eligible following assessment (Box 1) and\n16/20 (80%) were considered eligible for PrEP as an intervention for HIV prevention.\nPrEP uptake\nPrEP was taken up as a combined intervention for HBV treatment and HIV prophylaxis in 15/16\n(94%) of those eligible, while 1/16 (6.3%) decided not to take it. When investigating follow up\nand retention in care, out of the 14/15 (93.3%) that were due for a refill, 8/14 (57.1%) returned\nfor at least 1 refill, amongst whom 6/12 (50%) had two or more refills (Suppl figure 1). At the\ntime of follow-up for HBsAg positive individuals and on PrEP , the maximum followup time was 3\nmonths.\n5\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nDiscussion\nThis study provides a pilot assessment of HBV screening and offering PrEP as part of a\nprogram of SRH interventions for AYA in KZN, SA. WHO guidelines have been expanded with\nthe goal of reaching 40 million more people with HBV treatment by the year 2026, and provide\nflexibility for use of dual therapy TDF/XTC [2]. The use of TDF/XTC as a combination therapy for\nHIV PrEP and HBV treatment meets mandates for decentralisation and task-sharing [3], making\ninterventions more accessible to wider populations, and with potential cost-savings for health\nsystems. Capitalising on existing frameworks for HIV and SRH will improve pathways for\ndiagnosis and access to treatment.\nWe found a lower prevalence of active HBV infection (0.6%) compared to HBV prevalence rates\npreviously observed in individuals receiving HIV care, and high risk individuals (sex workers\n(SWs), men who have sex with men (MSM) and people who inject drugs (PWID)) in whom HBV\nprevalence is 8.5% and 4% respectively [16, 17]. Lower rates in the general population are in\nkeeping with the success of HBV vaccine roll-out as part of the WHO Expanded Programme on\nImmunization since the mid-1990’s. However, the results also reflect gaps in population HBV\nimmunity, with some AYA living with HBV, reflecting the lack of roll out of the birth dose vaccine,\nand possible gaps in coverage of the routine multivalent vaccine infant vaccine schedule.\nAmong the small number of diagnosed PLWHB, there was a high PrEP uptake but a fall-off in\nPrEP continuity over time.\nOne individual who had tested HBsAg-positive and was deemed PrEP eligible declined this\nintervention. The motives for not wishing to take PrEP were not investigated, but potential\nbarriers to PrEP uptake include pill burden, stigmatization, doubting the efficacy of PrEP , size of\nthe pill, concerns about side effects, myths and misconceptions about PrEP use, and costs of\nlong-term access (e.g. travelling or missed time from work to collect refills) [18].\nCaveats and limitations\nThe Theta Nami and LAPIS studies are successfully engaging a sexually active group with high\nPrEP eligibility. However, to date, we have only identified a small number of individuals who\nstarted PrEP as a combined intervention for HBV treatment and HIV prophylaxis. Although all\nyoung people in the communities targeted can access the SRH clinics, our data are not fully\nrepresentative of the whole community, as those who do not engage or opt out may have\nspecific vulnerabilities putting them at risk of blood-borne virus infections.\nLonger term aims\nFuture aims for HBV will include investigating the community’s acceptance of screening,\ntreatment and preventive interventions for HBV with qualitative research to determine\nknowledge, beliefs and experiences, and to identify and tackle barriers. There is a need for\ncontinuous evaluation of the impact of shifting HIV interventions on the HBV treatment\nlandscape, as HIV treatment moves towards dual therapy regimens (based on dolutegravir) and\nlong-acting injectable PrEP , neither of which currently incorporate HBV-active agents, nor have\n6\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nbeen clinically tested in people co-infected with HIV/HBV [19]. Long-term adherence to PrEP for\nPLWHB is important, as there are concerns about the potential for flares of HBV associated with\ntreatment interruptions [20], but in practice serious adverse events have not been described on\nPrEP cessation in PLWHB [4].\nPrEP is primarily used for HIV prevention but could also be expanded to individuals at risk of\nHBV. The integration of SRH, HIV and HBV services offers opportunities to combine education,\nscreening, family planning, delivery of perinatal care and prevention of mother to child\ntransmission (PMTCT) in keeping with the global ‘triple elimination agenda’ for HIV, HBV and\nsyphilis.\nConclusion\nThe framework we present here highlights opportunities to shape and integrate HBV education,\nprevention, diagnosis and treatment into wider SRH programs [3]. PrEP may be a valuable way\nfor delivering effective and consistent antiviral therapy to PLWHB, especially in settings in which\ninfrastructure for delivery of viral hepatitis care is currently limited or absent.\n7\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nFigures and tables\nFigure 1: Schematic structure of studies at the Africa Health Research Institute (AHRI) to\ninvestigate frameworks for delivery of sexual health services and HIV pre-exposure\nprophylaxis (PrEP) as a foundation for delivering testing and treatment for HBV. A:\nLocation of study sites; map shows South Africa with the KwaZulu-Natal province coloured gold\nand the two AHRI sites of Durban and Somkhele highlighted. B: Collaboration between PrEP\nstudies and HBV program. C: Pathway offered to adolescents and young adults showing HBV\nscreening, assessment, offer of PrEP and follow-up.\n8\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nTABLES\nTable 1: Characteristics of adolescents and young adults attending the ‘Thetha\nnami’/’LAPIS’ study mobile clinics in KwaZulu-Natal, classified by Hepatitis B surface\nantigen (HBsAg) status\nParticipant\ncharacteristic\nTotal cohort\nN=3,431\nHBsAg positive\nN=21\nHBsAg negative\nN=3,410 P-value1\nSex 0.465\nMale 1412/3431 (41.2%) 7/21 (33.3%) 1405/3410 (41.2%)\nFemale 2019/3431 (58.8%) 14/21 (66.7%) 2005/3410 (58.8%)\nAge (median, in years) 22 (19, 26) 29 (25, 30) 22 (19, 26) <0.001\nAge groups (in years) <0.001\n15 - 19 1019/3431 (29.7%) 0/21 (0.0%) 1019/3410 (29.9%)\n20 - 24 1295/3431 (37.8%) 3/21 (14.3%) 1292/3410 (37.9%)\n25 - 30 1114/3431 (32.5%) 18/21 (85.7%) 1096/3410 (32.2%)\nArea of residence 0.053\nRural 2712/3431 (79.0%) 13/21 (61.9%) 2699/3410 (79.1%)\nUrban/ Peri-urban 719/3431 (21%) 8/21 (38.1%) 711/3410 (20.9%)\n1 Chi-squared or exact p-value as appropriate\nHBsAg: Hepatitis B Virus surface antigen\n9\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nBox 1: PrEP eligibility and risk assessment questions based on South African National\nPrEP/ART guidelines [21]\nEligible for PrEP\n1. HIV negative\n2. Willing and able to take a pill a day?\n3. Willing to return for 3 monthly follow-ups?\n4. Understand that PrEP does not protect against pregnancy and STIs (contraception or\ncondoms needed)\nRisk assessment\n1. Participant at significant risk of acquiring HIV (adolescent and young person who\nwants PrEP due to self-perceived risk; key population – esp. if adolescent or young:\nHIV negative MSM or transgender person; engage in transactional sex or sex work;\nperson who inject drugs)\n2. 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Sexually Transmitted Infections Management Guidelines: Adapted the standard treatment\nguidelines and essential medicine list PHC.\nhttps://knowledgehub.health.gov.za/system/files/elibdownloads/2021-02/Primary%20Health\ncare%20STGs%20and%20EML%207th%20edition%20-%202020-v2.0.pdf. Accessed 20\nNov 2024\n16. Msomi N, Naidoo K, Yende-Zuma N, Padayatchi N, Govender K, Singh JA, Abdool-Karim\nS, Abdool-Karim Q, Mlisana K (2020) High incidence and persistence of hepatitis B virus\ninfection in individuals receiving HIV care in KwaZulu-Natal, South Africa. BMC Infect Dis\n20:1–9\n17. Scheibe A, Young K, Versfeld A, Wendy Spearman C, Sonderup M, Sing NP , Puren A,\nHausler H (2019) Hepatitis B, hepatitis C and HIV prevalence and related risk practices\namong key populations in South Africa: findings from a seven-city cross-sectional survey.\nhttps://doi.org/10.21203/rs.2.12025/v1\n18. Muhumuza R, Ssemata AS, Kakande A, et al (2021) Exploring Perceived Barriers and\nFacilitators of PrEP Uptake among Young People in Uganda, Zimbabwe, and South Africa.\nArch Sex Behav 50:1729–1742\n19. Mohareb AM, Kouamé MG, Nouaman M, et al (2024) What does the scale-up of long-acting\nHIV pre-exposure prophylaxis mean for the global hepatitis B epidemic? J Int AIDS Soc\n27:e26218\n20. Mohareb AM, Larmarange J, Kim AY , Coffie PA, Kouamé MG, Boyd A, Freedberg KA, Hyle\nEP (2022) Risks and benefits of oral HIV pre-exposure prophylaxis for people with chronic\nhepatitis B. Lancet HIV 9:e585–e594\n21. 2021 Updated guidelines for the provision of oral Pre-Exposure Prophylaxis (PrEP) to\npersons at substantial risk of HIV.\nhttps://knowledgehub.health.gov.za/system/files/elibdownloads/2022-08/PrEP%20Guideline\ns%20Update%2012%20%20Nov%20%202021%20Final.pdf. Accessed 20 Nov 2024\n12\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nSUPPLEMENTARY MATERIAL\nSupplementary methods\nStorage and collection of samples for sexually transmitted infection:\nSpecimen collection kits are kept at ambient range (18 - 25C). These kits are in a cooler box\nwith ice bricks when nurses are going to different collection sites. POCT (for syphilis and\nHBsAg) is done from a finger-prick by the nurse at the site of clinical review and recruitment.\nVaginal swab and urine samples were transported in a cooler box with ice bricks to the\nSomkhele laboratory. Urine is aliquoted into Xpert transport collection tubes and then stored\nrefrigerated (2 to 8C°). Vaginal swab samples were collected into Xpert transport tubes (at the\nclinic) and then refrigerated overnight in the Somkhele laboratory. Both urine and swabs were\nshipped to Durban refrigerated; once received in Durban, these samples are frozen (-20C°) until\ntesting.\n13\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nSupplementary tables:\nSupplementary Table 1: Relationship between hepatitis B surface antigen (HBsAg)\nstatus and sexually transmitted infections (STIs)\nSTI Characteristics Total\nN=3,431\nHBsAg positive\nN=21\nHBsAg negative\nN=3,410\nP-value†\nAny STI* 0.673\nNo 1639/2314 (70.8%) 14/21 (66.7%) 1625/2293 (70.9%)\nYes 675/2314 (29.2%) 7/21 (33.3%) 668/2293 (29.1%)\nChlamydia 0.302\nNo 1762/2312 (76.2%) 14/21 (66.7%) 1748/2291 (76.3%)\nYes 550/2312 (23.8%) 7/21 (33.3%) 543/2291 (23.7%)\nGonorrhoea 0.162\nNo 2157/2312 (93.3%) 18/21 (85.7%) 2139/2291 (93.4%)\nYes 155/2312 (6.7%) 3/21 (14.3%) 152/2291 (6.6%)\nTrichomonas‡ 0.618\nNo 1408/1513 (93.1%) 15/15 (100.0%) 1393/1498 (93.0%)\nYes 105/1513 (6.9%) 0/15 (0.0%) 105/1498 (7.0%)\nSyphilis 0.293\nNegative 3374/3430 (98.4%) 20/21 (95.2%) 3354/3409 (98.4%)\nPositive 56/3430 (1.6%) 1/21 (4.8%) 55/3409 (1.6%)\nEver treated any STI 0.609\nNo 115/675 (17.0%) 0/7 (0.0%) 115/668 (17.2%)\nYes 560/675 (83.0%) 7/7 (100.0%) 553/668 (82.8%)\n† Chi-squared or exact p-value\n* Any STI is the combination of common curable STIs in our setting (Chlamydia, Gonorrhoea, Trichomonas and\nSyphilis\n‡ Trichomonas is now being tested among female participants only\n14\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nSupplementary Table 2: PrEP uptake and retention according to Hepatitis B surface\nantigen (HBsAg) status among adolescent and young adult participants of sexual health\nscreening and prevention programmes in KwaZulu Natal, South Africa\nTotal\nN=3,431\nHBsAg positive\nN=21\nHBsAg negative\nN=3,410\nP-value*\nAssessed for PrEP eligibility 1.000\nNo 289/3431 (8.4%) 1/21 (4.8%) 288/3410 (8.4%)\nYes 3142/3431 (91.6%) 20/21 (95.2%) 3122/3410 (991.6%)\nEver eligible for PrEP 0.022\nNo 1467/3142 (46.7%) 4/20 (20.0%) 1463/3122 (46.9%)\nYes 1675/3142 (53.3%) 16/20 (80.0%) 1659/3122 (53.1%)\nEver started PrEP 0.008\nNo 638/1675 (38.1%) 1/16 (6.2%) 637/1659 (38.4%)\nYes 1037/1675 (61.9%) 15/16 (93.8%) 1022/1659 (61.6%)\nDue for first PrEP refill 0.110\nNo 8/1037 (0.8%) 1/15 (6.7%) 7/1022 (0.7%)\nYes 1029/1037 (99.2%) 14/15 (93.3%) 1015/1022 (99.3%)\nAt least one PrEP refill 0.163\nNo 627/1029 (60.9%) 6/14 (42.9%) 621/1015 (61.2%)\nYes 402/1029 (39.1%) 8/14 (57.1%) 394/1015 (38.8%)\nAt least two PrEP refills† 0.004\nNo 812/991 (81.9%) 6/12 (50.0%) 806/979 (82.3%)\nYes 179/991 (18.1%) 6/12 (50.0%) 173/979 (17.7%)\nFollow-up time (months)\n(mean, min, max)\n2.8 (0, 26) 7.8 (0, 22) 2.8 (0, 26) <0.001\nTime on PrEP (months)\n(mean, min, max)\n2.0 (0, 14) 1.7 (0, 3) 2.0 (0, 14) 0.384\nHBsAg: Hepatitis B Virus surface antigen; PrEP: Pre-exposure Prophylaxis.\n* Chi-squared or exact p-value\n† The denominator re\nfl\nects those who were due for their second PrEP re\nfi\nlls\n15\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint \n\nSupplementary figure 1: Care cascade summary of screening, linkage to care, receipt of\nPrEP and continuation of PrEP for young adults and adolescents accessing sexual and\nreproductive health services in a rural population in KwaZulu Natal, South Africa.\nN: number of people represented in each category of the care cascade; HBsAg: Hepatitis B\nsurface antigen; PrEP: Pre Exposure Prophylaxis (in this case used for HIV prophylaxis and\nHBV treatment).\n16\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted December 5, 2024. ; https://doi.org/10.1101/2024.11.29.24318178doi: medRxiv preprint","source_license":"CC-BY-4.0","license_restricted":false}