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The syndemic of HIV, sexually transmitted infections (STIs), and early pregnancy remain a key challenge to global public health. Decision-making around sexual and reproductive health (SRH) behaviours is critical to ensuring the uptake of biomedical technologies. Drawing from behavioural science theories, we propose a novel conceptual framework-the Decision Cascade-to describe the decision-making process that a user will go through as they navigate these decisions. Analogous to the HIV prevention and treatment cascade, this model describes key steps individuals go through when deciding to use HIV prevention technologies. Each step (being cued/triggered to act, reacting to the behaviour, evaluating the behaviour, assessing the feasibility of acting and the timing and final execution of the action), is influenced by a myriad of individual and socio-cultural factors, shaping the ultimate decision and behaviour outcome in a continual cycle. This framework has applications beyond HIV prevention, extending to other SRH technologies and treatments. By prioritizing human-centered design and understanding user decision-making intricacies, interventions can enhance effectiveness and address the complexities of SRH service uptake across diverse populations. The Decision Cascade framework offers a comprehensive lens to inform intervention design, emphasizing the need for nuanced approaches that resonate with the realities of decision-makers. Adopting such approaches is essential to achieving meaningful impact in HIV prevention and broader SRH initiatives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Heavy alcohol use among people living with HIV in sub-Saharan Africa can hinder the success of HIV treatment programmes, impacting progress towards United Nations Programme on HIV/AIDS goals. Primary partners can provide critical forms of social support to reduce heavy drinking and could be included in motivational interviewing (MI) interventions to address heavy drinking; however, few studies have evaluated MI interventions for couples living with HIV in sub-Saharan Africa. We aim to evaluate the feasibility and acceptability of a couple-based MI intervention with mobile breathalyser technology to reduce heavy alcohol use and improve HIV treatment outcomes among HIV-affected couples in South Africa., Methods and Analysis: We will employ a three-arm randomised controlled trial to assess the efficacy of couple-based MI (MI-only arm) and in conjunction with mobile breathalysers (MI-plus arm) to address alcohol use and HIV outcomes, as compared with enhanced usual care (control arm). We will enrol heterosexual couples aged 18-49 in a primary relationship for at least 6 months who have at least one partner reporting hazardous alcohol use and on antiretroviral therapy for 6 months. Participants in both MI arms will attend three manualised counselling sessions and those in the MI-plus arm will receive real-time feedback on blood alcohol concentration levels using a mobile breathalyser. Couples randomised in the control arm will receive enhanced usual care based on the South African ART Clinical Guidelines. Feasibility and acceptability indicators will be analysed descriptively, and exploratory hypotheses will be examined through regression models considering time points and treatment arms., Ethics and Dissemination: The study was approved by the University of California, San Francisco (HRPP; protocol number 21-35034) and Human Sciences Research Council Research Ethics Committee (REC: protocol number 1/27/20/21). We will disseminate the results at local community meetings, community-level health gatherings and conferences focused on HIV and alcohol use., Trial Registration Number: NCT05756790., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Traditional gender and social norms reinforce asymmetrical power relations, increase the risk of experiencing gender-based violence and mediate poor engagement with sexual and reproductive health services. This study explored gender norms and expectations amongst cisgender adolescents in rural KwaZulu-Natal, South Africa. A purposive sample of 29 adolescents aged 16-19 years old were enrolled as part of a longitudinal qualitative study. The current analysis reports on the first round of in-depth interviews, which focused on the role of men and women in their community. A theoretically informed thematic analysis identified three broad themes: 1) Adolescent interpretation and understanding of gender identity, 2) Gendered essentialism and Gender roles (two sub-themes: Young men: Power through providing, and Young women: The domestication process which highlighted that gender roles were defined by being the provider for men, and the successful fulfilment of traditional domestic behaviours amongst women), 3) Gender and fertility highlighted how participants highly valued fertility as affirming of manhood/womanhood. These norms reinforce gender roles that maintain asymmetrical power relations, carrying them over into adulthood. The subtle social pressure to prove fertility could have unintended consequences for driving teenage pregnancy. Structural, gender-based interventions emphasising positive gender-role development in early childhood are needed., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2024 Marshall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ensuring access to a package of integrated primary health care services is essential for achieving universal health coverage. In many countries, community health programs are necessary for primary health care service provision, but they are generally underfunded, and countries often lack the necessary evidence on costs and resource requirements. We conducted prospective cost analyses of community health programs in 6 countries in sub-Saharan Africa using the Community Health Planning and Costing Tool., Methods: The Community Health Planning and Costing Tool is a spreadsheet-based tool designed to cost key programmatic elements of community health services packages, including training, equipment, incentives, supervision, and management. In each country, stakeholders defined a package of community health services and corresponding standard treatment guidelines to estimate normative costs, which were applied to program scale-up targets. The data were entered into the tool, and cost models were prepared for different geographical and service utilization scenarios. The results were reviewed and validated with the governments, implementing partners, and expert panels. Additional scale-up scenarios were modeled, taking into account probable constraints to increasing community health service provision and potential funding limitations., Results: The services and scope of community health service packages varied by country, depending on contextual factors and determined health priorities. The package costs also varied significantly depending on the size and contents of the service package, the service delivery approach, the remuneration of the community health workers, and the cost of medicines and supplies., Conclusions: Community health programs and service packages are different in every country and change over time as they evolve. They should be routinely costed as an integral part of the planning and budgeting process and to ensure that sufficient resources are allocated for their effective and efficient implementation., (© Collins et al.)

Background: Adolescents and young women are at high risk for sexually transmitted infections (STIs) and unintended pregnancies. However, conversations about sexual and reproductive health (S&RH) are difficult and stigmatised. Visual art-based approaches have been a useful adjunct to language-dependent interviews, encouraging embodied memory recall. Here, we explored a novel visual art-based methodology-"Stories from the Edge"-with a cohort of young women to understand how artmaking might facilitate dialogue of how S&RH experiences influenced behaviour, to enrich dialogues captured in the individual in-depth interviews (IDIs)., Methods: Seven isiXhosa-speaking young women (aged 21-25 years) were recruited into a six-session art-based engagement, painting the stories of their S&RH experiences. Large format artmaking and IDIs contributed to the data set. IDIs were audio recorded, transcribed, and translated and then analysed thematically., Results: Young women felt that the visual art-based methodology eased barriers to communicating experiences of S&RH-seeking behaviours, with one woman commenting that "words are too small" to capture lived experiences. Artmaking provided the opportunity to express emotional complexities of the pleasures of intimate relationships and the heartbreak of betrayal for which they had no language. Significant social relationships (family, partners, peers) influenced sexual and reproduction attitudes and practices more than healthcare facilities and staff and more distal socio-cultural attitudes/practices. These influences shifted from adolescence to adulthood-from family to peer and partners., Conclusion: Young women valued using the art-based methodology, which facilitated recall and verbalising their S&RH experiences more fully than language-only research. The process outlined here could provide a creative method that builds communication skills to negotiate the needs and desires of young women with partners and staff at S&RH services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LM declared a past coauthorship with the authors J-AP and L-GB., (© 2023 Hartley, Knight, Humphries, Trappler, Gill, Bekker, MacKenny and Passmore.)

Background: In sub-Saharan Africa, high HIV incidence rates in adolescent girls and young women (AGYW) persist despite extensive HIV prevention efforts., Methods: A prospective cohort of 2,710 HIV-negative AGYW (15-24 years) in KwaZulu-Natal, South Africa were interviewed at baseline and followed-up approximately 18 months later (2014-2017). Associations between HIV seroconversion and socio-demographic and behavioural variables measured at baseline and follow-up were examined using Cox regression and a proximate determinants framework. Inter-relationships between determinants were measured using logistic regression. Separate models were built for 15-19 and 20-24-year-olds., Results: Weighted HIV incidence was 3.92 per 100 person-years (95% confidence interval: 3.27-4.69; 163 seroconversions over 4,016 person-years). Among 15-19-year-olds, absence of family support (adjusted hazards ratio (aHR): 3.82 (1.89-7.72)), having a circumcised partner (aHR: 0.5 (0.27-0.94)) or one who was HIV-positive and not on antiretroviral therapy (ART) (aHR: 6.21 (2.56-15.06)) were associated with HIV incidence. Those reporting an absence of family support were also more likely to report >1 partner during follow-up (odds ratio (OR): 2.7(1.11-6.57)). Among 20-24-year-olds, failure to complete secondary school (aHR: 1.89 (1.11-3.21)), inconsistent condom use (aHR: 3.01 (1.14-7.96)) and reporting partner(s) who were HIV-positive and not on ART (aHR: 7.75 (3.06-19.66)) were associated with HIV incidence. Failure to complete secondary school among 20-24-year-olds was associated with inconsistent condom use (OR: 1.82 (1.20-2.77)) and reporting an HIV-positive partner not on ART (OR: 3.53(1.59-7.82)) or an uncircumcised partner (OR: 1.39 (1.08-1.82)., Conclusion: Absence of family support and incomplete schooling are associated with risky sexual behaviours and HIV acquisition in AGYW. In addition, partner-level prevention-condom use, medical circumcision, and viral suppression-continue to play an important role in reducing HIV risk in AGYW. These findings support the use of combination HIV prevention programs that consider structural as well as biological and behavioural HIV risk factors in their design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lewis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants., Competing Interests: The authors have declared that no competing interests exist.

Tuberculosis (TB) remains a global health problem and there is an ongoing effort to develop more effective therapies and new combination regimes that can reduce duration of treatment. The purpose of this study was to demonstrate utility of a physiologically-based pharmacokinetic modeling approach to predict plasma and lung concentrations of 11 compounds used or under development as TB therapies (bedaquiline [and N-desmethyl bedaquiline], clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, linezolid, pyrazinamide, rifampicin, and rifapentine). Model accuracy was assessed by comparison of simulated plasma pharmacokinetic parameters with healthy volunteer data for compounds administered alone or in combination. Eighty-four percent (area under the curve [AUC]) and 91% (maximum concentration [C max ]) of simulated mean values were within 1.5-fold of the observed data and the simulated drug-drug interaction ratios were within 1.5-fold (AUC) and twofold (C max ) of the observed data for nine (AUC) and eight (C max ) of the 10 cases. Following satisfactory recovery of plasma concentrations in healthy volunteers, model accuracy was assessed further (where patients' with TB data were available) by comparing clinical data with simulated lung concentrations (9 compounds) and simulated lung: plasma concentration ratios (7 compounds). The 5th-95th percentiles for the simulated lung concentration data recovered between 13% (isoniazid and pyrazinamide) and 88% (pyrazinamide) of the observed data points (Am J Respir Crit Care Med, 198, 2018, 1208; Nat Med, 21, 2015, 1223; PLoS Med, 16, 2019, e1002773). The impact of uncertain model parameters, such as the fraction of drug unbound in lung tissue mass (fu mass ), is discussed. Additionally, the variability associated with the patient lung concentration data, which was sparse and included extensive within-subject, interlaboratory, and experimental variability (as well interindividual variability) is reviewed. All presented models are transparently documented and are available as open-source to aid further research., (© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Providing viral load (VL) results to people living with HIV (PLHIV) on antiretroviral therapy (ART) remains a challenge in low and middle-income countries. Point-of-care (POC) VL testing could improve ART monitoring and the quality and efficiency of differentiated models of HIV care. We assessed the acceptability of POC VL testing within a differentiated care model that involved task-shifting from professional nurses to less highly-trained enrolled nurses, and an option of collecting treatment from a community-based ART delivery programme., Methods: We undertook a qualitative sub-study amongst clients on ART and nurses within the STREAM study, a randomized controlled trial of POC VL testing and task-shifting in Durban, South Africa. Between March and August 2018, we conducted 33 semi-structured interviews with clients, professional and enrolled nurses and 4 focus group discussions with clients. Interviews and focus groups were audio recorded, transcribed, translated and thematically analysed., Results: Amongst 55 clients on ART (median age 31, 56% women) and 8 nurses (median age 39, 75% women), POC VL testing and task-shifting to enrolled nurses was acceptable. Both clients and providers reported that POC VL testing yielded practical benefits for PLHIV by reducing the number of clinic visits, saving time, travel costs and days off work. Receiving same-day POC VL results encouraged adherence amongst clients, by enabling them to see immediately if they were 'good' or 'bad' adherers and enabled quick referrals to a community-based ART delivery programme for those with viral suppression. However, there was some concern regarding the impact of POC VL testing on clinic flows when implemented in busy public-sector clinics. Regarding task-shifting, nurses felt that, with extra training, enrolled nurses could help decongest healthcare facilities by quickly issuing ART to stable clients. Clients could not easily distinguish enrolled nurses from professional nurses, instead they highlighted the importance of friendliness, respect and good communication between clients and nurses., Conclusions: POC VL testing combined with task-shifting was acceptable to clients and healthcare providers. Implementation of POC VL testing and task shifting within differentiated care models may help achieve international treatment targets., Trial Registration: NCT03066128 , registered 22/02/2017.

Background: Understanding sexual activity is necessary to prevent sexually transmitted infections. Evidence from Sub-Saharan Africa suggests that 10-20% of youth aged 15-24 are sexually active before reaching 15 years, yet estimating sexual activity remains challenging. This study explored the use of multiple sexual health outcomes to identify sexually-active young women in rural KwaZulu-Natal, South Africa., Methods: Using a multi-component sexual activity profile (MSAP), we aimed to identify sexually active students. Based on data from 2675 grade 9 and 10 students attending 14 high schools) in rural KwaZulu-Natal, we constructed a descriptive diagram identifying students who were sexually active by self-report vs MSAP profile. T-tests for two independent samples was performed to compare by sex and ecological variables that characterise students newly-identified as sexually active., Results: Using self-report only, 40.3% self-reported as sexually active, whilst the MSAP identified 48.7% (223 additional students). More females were identified than males. Younger adolescents were more likely to underreport sexual activity but were identified using MSAP. Newly-identified as sexually active were more likely to be female (p = < 0.000), 15 years old or younger (p = 0.008), less likely to perceive being at risk (p = 0.037) or have ever used alcohol (p = < 0.000). At a relational level, they were less likely to report having ever had a boyfriend/girlfriend (p = 0.000) or to have felt pressured to have sex by their peers (p = < 0.000) or partners (p = 0.008). At a familial level they more likely to be of medium socioeconomic (SES) status (p = 0.037) whilst at a school and community level they were less likely to have repeated a grade (p = 0.024) and were more likely to be engaged in social activities (p = 0.032)., Conclusions: The MSAP profile identified more potentially sexually active students, and gave insight into the characteristics of students who may be unwilling to self-report sexual activity Future work should investigate how this approach could enhance and describe sexually-active adolescents for research and healthcare provision.

Purpose: Young women are at high risk for negative sexual health outcomes. Despite their high risk, many sexually-active women never experience negative sexual health outcomes. This study explored the ecological risk factors associated with the risk profiles of sexually-active female high school-learners in rural KwaZulu-Natal, South Africa., Methods: Using baseline data from N = 596 sexually-active school-going women, we explored the ecological factors associated with being sexually-active and managing risk successfully [SARS] or unsuccessfully [SARU]. Generalised estimated equations (GEE) were applied to data collected at multiple levels while adjusting for school and other included variables. GEE were used to calculate probability of being SARU., Results: Amongst SARU learners, 21.9% had HIV, 38.6% had HSV-2, 12.5% were pregnant, 28.7% self-reported STI symptoms and 51.9% reported a previous pregnancy. Individual-level factors had the greatest impact on being SARU. Univariate and multivariate analysis highlighted several important partner factors associated with SARU. Age was significantly associated with the risk profiles (p<0.0001), a greater proportion of SARU learners were 18 or older compared to the SARS learners. The odds of being SARU decreased when ≥18 years (aOR = 0.2577, 95% CI 0.1462-0.4542) or if not falling pregnant was important (aOR = 0.6343, 95% CI 0.4218-0.9538). Having >1 HIV test (aOR = 2.2161, 95% CI 1.3964-3.5169) increased the odds a SARU profile., Conclusion: Individual and partner level factors are important for the sexual health profile of an adolescent female. While the exploratory findings require further research; managing multiple sexual health outcomes, tailoring responses around a risk profile and including partners is essential for successful interventions.

Background: Group B Streptococcus (GBS) is a major cause of mortality and morbidity in infants and is associated with transmission from a colonized mother at birth and via infected breastmilk. Although maternal/infant colonization with GBS is common, the majority of infants exposed to GBS remain unaffected. The association between breastmilk immune factors and infant colonization and disease prevention has not been elucidated., Objectives: We have investigated the association between SIgA and cytokines in breastmilk and infant GBS colonization and clearance., Methods: Mother/infant GBS colonization was determined in a prospective cohort of 750 Gambian mother/infant pairs followed to day 89 of life. Anti-GBS secretory IgA bound to the surface of whole bacteria was assessed by flow cytometry and a panel of 12 cytokines quantified by mesoscale discovery in colostrum, breastmilk and serum., Results: Compared with infants receiving low anti-GBS SIgA in colostrum, infants receiving high anti-GBS SIgA were at decreased risk of GBS colonization for serotypes III and V. Infants colonized at day 6 were twice as likely to receive colostrum with high TGF-β1, TNFα, IL10, and IL-6 compared to uncolonized infants. Infants receiving high colostral TGF-β1, TNFα, and IL-6 had two-fold enhanced GBS clearance between birth and day 89., Conclusion: Our results suggest that the infant GBS colonization risk diminishes with increasing anti-GBS SIgA antibody in breastmilk and that key maternally derived cytokines might contribute to protection against infant colonization. These findings might be leveraged to develop interventions including maternal vaccination that may reduce infant GBS colonization.

Background: Acquired myasthenia gravis (MG) in cats most commonly causes generalized weakness without megaesophagus and is more often associated with a cranial mediastinal mass, compared to dogs., Hypothesis/objectives: To extend the clinical findings described in the report of 2000 on MG in cats (J Am Vet Med Assoc 215:55-57)., Animals: Two hundred and thirty-five cats with MG., Methods: Retrospective case study to evaluate the long-term outcome and incidence of spontaneous remission in myasthenic cats. Information including signalment, clinical presentation, presence of and type of cranial mediastinal mass, treatment including surgical versus medical, survival time, and outcome including spontaneous remissions was collected and analyzed in cats diagnosed at the Comparative Neuromuscular Laboratory, University of California San Diego by detection of acetylcholine receptor antibody titers >0.3 nmol/L by immunoprecipitation radioimmunosassay., Results: Acquired MG in cats is associated with a euthanasia rate of 58%. Abyssinian and Somali cats had an increased incidence of MG compared to mixed breed cats or cats of other breeds. A cranial mediastinal mass, most commonly thymoma, was observed in 52% of the cats, which is higher than in the previous report. Spontaneous remission is not a characteristic of MG in cats., Conclusions and Clinical Importance: Myasthenia gravis in cats is a chronic disease associated with a high incidence of a cranial mediastinal mass. Spontaneous remission is not common and clinicians should warn owners of the necessity for long-term treatment. The clinical outcome with a cranial mediastinal mass did not differ between surgical or medical treatment., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.)

Background: Young people in South Africa are at high risk of HIV infection and yet may have more limited access to prevention and treatment services than others in the population. Testing facilitates the sharing of prevention messages but also enables the linkage to care and treatment of those who test positive and therefore has wider public health implications., Methods: This baseline survey conducted in 2005 for a community randomized trial in rural KwaZulu-Natal explored factors associated with a history of ever, repeat and recent testing amongst sexually debuted men and women aged 18 to 32 years., Results: Over 35% of this rural population ever tested for HIV, with men less likely to ever (unadjusted OR 0.26, 95% CI: 0.21-0.32) and repeatedly test than women (adjusted OR (aOR) 0.68, 95% CI: 0.48-0.97). Men aged 24-28 years (aOR 2.02, 95% CI: 1.10-3.71) and 29-32 years (aOR 2.69, 95% CI: 1.46-4.94) were more likely to ever test than those <20 years. Those who reported having discussed HIV with others had significantly greater odds of reporting ever (men's aOR 2.83, 95% CI: 1.63-4.89; women's aOR 3.36, 95% CI: 2.50-4.53), recent (irrespective of sex, aOR 2.87, 95% CI: 2.02-4.09) and repeat testing (aOR 2.02, 95% CI: 1.28-3.19)., Conclusion: These findings highlight the need for novel youth- and men-friendly testing services and emphasises the importance of discussions about HIV in the home and community to encourage testing.

Background: Epidemiological data from South Africa demonstrate that risk of human immunodeficiency virus (HIV) infection in males increases dramatically after adolescence. Targeting adolescent HIV-negative males may be an efficient and cost-effective means of maximising the established HIV prevention benefits of voluntary medical male circumcision (VMMC) in high HIV prevalence-, low circumcision practice-settings. This study assessed the feasibility of recruiting male high school students for VMMC in such a setting in rural KwaZulu-Natal., Methods and Findings: Following community and key stakeholder consultations on the acceptability of VMMC recruitment through schools, information and awareness raising sessions were held in 42 high schools in Vulindlela. A three-phase VMMC demand-creation strategy was implemented in partnership with a local non-governmental organization, ZimnadiZonke, that involved: (i) community consultation and engagement; (ii) in-school VMMC awareness sessions and centralized HIV counselling and testing (HCT) service access; and (iii) peer recruitment and decentralized HCT service access. Transport was provided for volunteers to the Centre for the AIDS Programme of Research in South Africa (CAPRISA) clinic where the forceps-guided VMMC procedure was performed on consenting HIV-negative males. HIV infected volunteers were referred to further care either at the CAPRISA clinic or at public sector clinics. Between March 2011 and February 2013, a total of 5165 circumcisions were performed, the majority (71%) in males aged between 15 and 19 years. Demand-creation strategies were associated with an over five-fold increase in VMMC uptake from an average of 58 procedures/month in initial community engagement phases, to an average of 308 procedures/month on initiation of the peer recruitment-decentralized service phase. Post-operative adverse events were rare (1.2%), mostly minor and self-resolving., Conclusions: Optimizing a high volume, adolescent-targeted VMMC program was feasible, acceptable and safe in this setting. Adaptive demand-creation strategies are required to sustain high uptake.