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Background: Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset. Methods: In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min. Findings: We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13 523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22–1·81; I2=25%) and grade 2 and higher events (OR 1·75, 0·68–4·49; I2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18 676 individuals from 15 countries (1453 [7·8%] from RCTs) and 79 (0·42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14 368 PrEP users and 349 (2·43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60·00–89·99 mL/min (adjusted hazard ratio [aHR] 8·49, 95% CI 6·44–11·20) and less than 60 mL/min (aHR 20·83, 12·83–33·82). Interpretation: RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use. Funding: Unitaid, Bill & Melinda Gates Foundation, WHO.

HIV treatment and prevention as well as other chronic disease care can require regular kidney function assessment based on a creatinine test. To assess the costs of creatinine testing in a public health care system, we conducted activity-based costing during a HIV pre-exposure prophylaxis (PrEP) demonstration project in the Hhohho region of Eswatini. Resource use was assessed by a laboratory technician and valued with government procurement prices, public sector salaries, and own cost estimates. Obtaining a blood sample in a clinic and performing a creatinine test in a high-throughput referral laboratory ( 660,000 blood tests, including 120,000 creatinine tests, in 2018) were estimated to have cost, on average, $1.98 in 2018. Per test, $1.95 were variable costs ($1.38 personnel, ¢39 consumables, and ¢18 other costs) and ¢2.6 were allocated semi-fixed costs (¢1.1 laboratory equipment, ¢0.85 other, ¢0.45 consumables, and ¢1.3 personnel costs). Simulating different utilization of the laboratory indicated that semi-fixed costs of the laboratory (e.g., equipment purchase or daily calibration of the chemistry analyzer) contributed less than variable costs (e.g., per-test personnel time and test reagents) to the average creatinine test cost when certain minimum test numbers can be maintained. Our findings suggest, first, lower creatinine testing costs than previously used in cost and cost-effectiveness analyses of HIV services and, second, that investment in laboratory equipment imposed a relatively small additional cost on each performed test in the high-throughput referral laboratory.El tratamiento y la prevención del VIH, así como el cuidado de otras enfermedades crónicas, pueden requerir una evaluación periódica de la función renal basada en una prueba de creatinina. Para evaluar los costes de las pruebas de creatinina en un sistema de atención sanitaria público, realizamos un cálculo de costes basado en actividades durante un proyecto de demostración de profilaxis preexposición al VIH (PrEP) en la región de Hhohho de Eswatini. El uso de los recursos fue evaluado por un técnico de laboratorio y valorado con los precios de adquisición del gobierno, los salarios del sector público y las estimaciones de costes propias. La obtención de una muestra de sangre en una clínica y la realización de una prueba de creatinina en un laboratorio de referencia de alto rendimiento ( 660.000 pruebas de sangre, incluidas 120.000 pruebas de creatinina, en 2018) se estimó que habían costado, en promedio, $1,98 en 2018. Por prueba, $1,95 eran costes variables ($1,38 de personal, ¢39 de consumibles y ¢18 de otros costes) y ¢2,6 eran costes semifijos asignados (¢1,1 de equipamiento de laboratorio, ¢0,85 de otros, ¢0,45 de consumibles y ¢1,3 de personal). La simulación de utilización diferente del laboratorio indicó que los costes semifijos del laboratorio (por ejemplo, la compra de equipos o la calibración diaria del analizador químico) contribuyeron menos que los costes variables (por ejemplo, el tiempo del personal por prueba y los reactivos de la prueba) al coste medio de la prueba de creatinina cuando se pueden mantener ciertos números mínimos de pruebas. Nuestros resultados sugieren, en primer lugar, que los costes de las pruebas de creatinina son inferiores a los utilizados anteriormente en los análisis de coste y costo-efectividad de los servicios de VIH y, en segundo lugar, que la inversión en equipos de laboratorio supuso un coste adicional relativamente pequeño en cada prueba realizada en el laboratorio de referencia de alto rendimiento.

BackgroundMinors who sell sex are likely to have complex mental health needs that may persist into adulthood. This topic is understudied in Sub-Saharan Africa. This study hypothesized that adult female sex workers in Eswatini who started selling sex as minors have a higher prevalence of depression than those who started as adults. We also examined correlates of depression and underage initiation of selling sex, including stigma and condom-related behaviors.MethodsFrom October-December 2014, women aged 18 or older who sold sex in the past 12 months in Eswatini were recruited through venue-based sampling. Participants completed a survey including the 9-item Patient Health Questionnaire (PHQ-9) and a question about the age at which they first sold sex for money. T-tests, χ2 tests and multivariable logistic regression were used to assess associations.ResultsOverall, 43.1% of participants (332/770) had probable depression, and 16.6% (128/770) started selling sex as minors under the age of 18. Over half (55.5%, 71/128) of those who started selling sex as minors had depression. This was significantly higher than the 40.7% (261/642) prevalence of depression among participants who started selling sex as adults (p=0.002). After adjusting for confounders, female sex workers who started selling sex as minors had higher odds of depression than those who started as adults (adjusted odds ratio 1.70, 95% confidence interval 1.11-2.60). Both depression and underage initiation of selling sex were associated with anticipating stigma toward sex workers in healthcare settings and the number of times the participant reported a condom slipped off or broke in the past month.ConclusionResults highlight the need for trauma-informed and adolescent-friendly mental health services in settings free of stigma toward female sex workers in Eswatini.

People in receipt of pre-exposure prophylaxis (PrEP) for the prevention of HIV in Sub-Saharan Africa often discontinue taking the medication. We conducted 27 semi-structured interviews with men and women who had started PrEP but did not return to the clinic for a refill after a 1, 2 or 3-month period. These 'discontinuation' clients were enrolled in a PrEP demonstration project for the general population in nurse-led, public-sector, primary-care clinics in Eswatini. Reasons for discontinuation included changes to self-perceived HIV risk such as the end of pregnancy and absent partners. Others described PrEP as inaccessible when working away from home and many described difficulties relating to a daily pill regimen and managing side effects. Female clients described being prohibited from using PrEP by their partners and co-wives. From these results, we recommend that client-centred counselling stresses the prevention-effective adherence paradigm, which promotes PrEP use in risk periods that are identifiable and PrEP discontinuation when the risk period has finished. A national scale up of PrEP may mitigate problems accessing PrEP. Extended counselling and support could assist with adherence and the management of side effects. Education and support for partners and families of PrEP clients may also contribute to better PrEP continuation.

Due to the high HIV incidence among the general population of Eswatini, pre-exposure prophylaxis (PrEP) for HIV-exposed individuals is recommended. However, little is known about PrEP uptake and preferences in PrEP delivery healthcare setting among the general population. We conducted a secondary analysis of a randomized trial that aimed to increase PrEP uptake. All clients eligible for PrEP in one of six public-sector healthcare facilities in Eswatini were included. PrEP uptake was stratified by initial reason for visit (e.g. outpatient). Preferences in PrEP delivery setting were collected among those clients who initiated PrEP. A total of 1782 clients had their HIV acquisition risk assessed. Of these, 72% (1277/1782) were considered at risk by healthcare providers and, among them, 40% (517/1277) initiated PrEP. Uptake was higher among clients visiting specifically to initiate PrEP (93%), followed by HIV testing visits (45.8%) and outpatient visits (40%). Among those who initiated PrEP, preferred delivery settings were outpatient services (31%), HIV testing services (26%), family planning (21%) and antenatal services (14%). Men or those at high risk of HIV acquisition were more likely to prefer HIV testing and outpatient services, while young women were more likely to visit and express a preference for antenatal and family planning services. Outpatient services and HIV testing services could be preferable choices for PrEP delivery integration, due to the high PrEP uptake and delivery setting preferences of the populations who use these services. Antenatal and family planning could also be considered with a view to targeting the youngest women.Debido a la alta incidencia del VIH entre la población general de Eswatini, se recomienda la profilaxis previa a la exposición (PrEP) para las personas expuestas al VIH. Sin embargo, se sabe poco sobre la aceptación de la PrEP y las preferencias en el ámbito de la atención sanitaria de la PrEP entre la población general. Se realizó un análisis secundario de un ensayo clínico que pretendía aumentar la aceptación de la PrEP. Se incluyó a todos los clientes elegibles para la PrEP en uno de los seis centros sanitarios del sector público de Eswatini. La aceptación de la PrEP se estratificó según el motivo inicial de la visita (por ejemplo, paciente externo). Se recogieron las preferencias en el entorno de administración de la PrEP entre aquellos clientes que iniciaron la PrEP. Se evaluó el riesgo de adquisición del VIH de un total de 1.782 clientes (de 2.238 contactados, el 80%). De ellos, el 72% (1277/1782) fueron considerados de riesgo por los profesionales sanitarios y, entre ellos, el 40% (517/1277) iniciaron la PrEP. El consumo fue mayor entre los clientes que acudieron específicamente para iniciar la PrEP (93%), seguido de las visitas para realizar la prueba del VIH (45,8%) y las visitas ambulatorias (40%). Entre los que iniciaron la PrEP, los entornos de prestación preferidos fueron los servicios ambulatorios (31%), los servicios de pruebas del VIH (26%), la planificación familiar (21%) y los servicios prenatales (14%). Los hombres o las personas con alto riesgo de contraer el VIH tenían más probabilidades de preferir las pruebas del VIH y los servicios ambulatorios, mientras que las mujeres jóvenes tenían más probabilidades de acudir a los servicios prenatales y de planificación familiar y expresar su preferencia por ellos. Los servicios ambulatorios y los servicios de pruebas del VIH podrían ser opciones preferibles para la integración de la entrega de la PrEP, debido a la alta aceptación de la PrEP y a las preferencias del entorno de entrega de las poblaciones que utilizan estos servicios. Los servicios prenatales y de planificación familiar también podrían considerarse con vistas a dirigirse a las mujeres más jóvenes.

Information regarding HIV pre-exposure prophylaxis (PrEP) for the general population is largely lacking, because the majority of PrEP demonstration projects have focused on key populations. This qualitative study examines barriers and facilitators to PrEP uptake and adherence among the general population in Eswatini, where PrEP is offered through public-sector primary-care clinics. We analysed 106 semi-structured in-depth interviews with healthcare workers (

Background: Previous World Health Organization (WHO) guidance on tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards. Creatinine screening may represent barriers to PrEP implementation and uptake. We systematically reviewed published literature on renal toxicity among PrEP users and conducted an individual patient data meta-analysis (IPDMA) on kidney function among PrEP users in a global data set. Methods: Meta-analyses were conducted on published data to estimate pooled relative risks of grade 1+ and 2+ kidney-related adverse events among PrEP users. The IPDMA included data on PrEP users from 19 PrEP programmes. Estimated creatinine clearance at baseline and change in creatinine clearance after PrEP initiation were described by age, gender, and comorbidities. Random-effects regressions estimated risk in decline in creatinine clearance to

Clinical trials have shown that antiretroviral drugs used as pre-exposure prophylaxis (PrEP) are highly effective for preventing HIV acquisition. PrEP efforts, including in sub-Saharan Africa, have almost exclusively focused on certain priority groups, particularly female sex workers, men having sex with men, pregnant women, serodiscordant couples, and young women. As part of a PrEP demonstration project involving the general population at six primary health care facilities in Eswatini (formerly Swaziland), we conducted a randomized trial of a health care facility-based PrEP promotion package designed to increase PrEP uptake. Over the 18-month study duration, 33.6% (517 of 1538) of adults identified by health care workers as being at risk of acquiring HIV took up PrEP, and 30.0% of these individuals attended all scheduled appointments during the first 6 months after initiation of PrEP. The PrEP promotion package was associated with a 55% (95% confidence interval, 15 to 110%; P = 0.036) relative increase in the number of individuals taking up PrEP, with an absolute increase of 2.2 individuals per month per health care facility. When asked how PrEP uptake could be improved in 217 accompanying in-depth qualitative interviews, interviewees recommended an expansion of PrEP promotion activities beyond health care facilities to communities. Although a health care facility-based promotion package improved PrEP uptake, both uptake and retention remained low. Expanding promotion activities to the community is needed to achieve greater PrEP coverage among adults at risk of HIV infection in Eswatini and similar settings.

BackgroundImplementation evidence for pre-exposure prophylaxis (PrEP) for the general population in primary-care clinics in Southern Africa is limited. Perspective from those providing PrEP in ‘real world’ settings is needed to better inform future programming, policy, and scale up. MethodsFrom September 2017 to January 2019 we conducted 54 semi-structured in-depth interviews with purposively selected healthcare workers (HCWs) from six public sector, nurse-led, primary-care clinics in Eswatini. Data from observational notes, daily debriefing sessions and interview transcripts were analyzed using Nvivo 12 following the tenets of Grounded Theory. We present our results within six domains of a modified Consolidated Framework for Implementation (CFIR). ResultsHCWs said that they adapted implementation guidelines in order to inform more people of PrEP. HCWs said that clinic and community based PrEP education and promotion was essential for demand creation, uptake and continued PrEP use. Clinic modifications included conducting PrEP risk assessments during existing TB screening services, and targeting PrEP counselling for pregnant women and clients with sexually transmitted infections. HCWs described streamlining the PrEP initiation process by fast-tracking at-risk clients for initiation and pill collection. HCW said they emphasised PrEP as being for ‘everyone’ to avoid stigma. ConclusionsIntegration of PrEP delivery into existing screening and treatment services may help reach those most vulnerable to HIV infection, avoid time-consuming referrals, and prevent loss of clients between different components of the care continuum. PrEP education and promotion should be both clinic and community based to ensure potential clients have enough information before reaching the clinic, prevent PrEP-associated stigma and assist in family and partner understanding of PrEP use. HCWs providing PrEP in public-sector clinics have first-hand knowledge of implementation in ‘real world’ settings in a field where policy and program implementation is largely undefined. Integrating their feedback into future programming and policy may support effective PrEP delivery in Eswatini and other high prevalence settings in Southern Africa.

Background: Epidemiological data are needed to characterize the age-specific HIV burden and engagement in HIV services among young, marginalized women in sub-Saharan Africa. Setting: Women aged ≥18 years who reported selling sex were recruited across 9 countries in Southern, Central, and West Africa through respondent driven sampling (N = 6592). Methods: Individual-level data were pooled and age-specific HIV prevalence and antiretroviral therapy (ART) coverage were estimated for each region using generalized linear mixed models. HIV-service engagement outcomes (prior HIV testing, HIV status awareness, and ART use) were compared among women living with HIV across age strata (18–19, 20–24, and ≥25 years) using generalized estimating equations. Results: By age 18%–19%, 45.4% [95% confidence interval (CI): 37.9 to 53.0], 5.8% (95% CI: 4.3 to 7.8), and 4.0% (95% CI: 2.9 to 5.4) of young women who sell sex were living with HIV in Southern, Central, and West Africa respectively. Prevalence sharply increased during early adulthood in all regions, but ART coverage was suboptimal across age groups. Compared with adult women ≥25, young women aged 18–19 were less likely to have previously tested for HIV [prevalence ratio (PR) 0.76; 95% CI: 0.72 to 0.80], less likely to already be aware of their HIV status (PR 0.48; 95% CI: 0.35 to 0.64), and less likely to be taking ART (PR 0.67; 95% CI: 0.59 to 0.75). Conclusions: HIV prevalence was already high by age 18–19 in this pooled analysis, demonstrating the need for prevention efforts that reach women who sell sex early in their adolescence. ART coverage remained low, with women in the youngest age group the least engaged in HIV-related services. Addressing barriers to HIV service delivery among young women who sell sex is central to a comprehensive HIV response

Introduction Oral pre‐exposure prophylaxis (PrEP) provision is a priority intervention for high HIV prevalence settings and populations at substantial risk of HIV acquisition. This mathematical modelling analysis estimated the impact, cost and cost‐effectiveness of scaling up oral PrEP in 13 countries. Methods We projected the impact and cost‐effectiveness of oral PrEP between 2018 and 2030 using a combination of the Incidence Patterns Model and the Goals model. We created four PrEP rollout scenarios involving three priority populations—female sex workers (FSWs), serodiscordant couples (SDCs) and adolescent girls and young women (AGYW)—both with and without geographic prioritization. We applied the model to 13 countries (Eswatini, Ethiopia, Haiti, Kenya, Lesotho, Mozambique, Namibia, Nigeria, Tanzania, Uganda, Zambia and Zimbabwe). The base case assumed achievement of the Joint United Nations Programme on HIV/AIDS 90‐90‐90 antiretroviral therapy targets, 90% male circumcision coverage by 2020 and 90% efficacy and adherence levels for oral PrEP. Results In the scenarios we examined, oral PrEP averted 3% to 8% of HIV infections across the 13 countries between 2018 and 2030. For all but three countries, more than 50% of the HIV infections averted by oral PrEP in the scenarios we examined could be obtained by rollout to FSWs and SDCs alone. For several countries, expanding oral PrEP to include medium‐risk AGYW in all regions greatly increased the impact. The efficiency and impact benefits of geographic prioritization of rollout to AGYW varied across countries. Variations in cost‐effectiveness across countries reflected differences in HIV incidence and expected variations in unit cost. For most countries, rolling out oral PrEP to FSWs, SDCs and geographically prioritized AGYW was not projected to have a substantial impact on the supply chain for antiretroviral drugs. Conclusions These modelling results can inform prioritization, target‐setting and other decisions related to oral PrEP scale‐up within combination prevention programmes. We caution against extensive use given limitations in cost data and implementation approaches. This analysis highlights some of the immediate challenges facing countries—for example, trade‐offs between overall impact and cost‐effectiveness—and emphasizes the need to improve data availability and risk assessment tools to help countries make informed decisions.

IntroductionAs HIV is very effectively acquired during condomless receptive anal intercourse (AI) with serodiscordant and viremic partners, the practice could contribute to the high prevalence among female sex workers (FSW) in eSwatini (formerly known as Swaziland). We aim to estimate the proportion reporting AI (AI prevalence) among Swazi FSW and to identify the correlates of AI practice in order to better inform HIV prevention interventions among this population.MethodsUsing respondent-driven sampling (RDS), 325 Swazi FSW were recruited in 2011. We estimated the prevalence of AI and AI with inconsistent condom use in the past month with any partner type, and inconsistent condom use during AI and vaginal intercourse (VI) by partner type. Univariate and multivariable logistic regression models were used to identify behavioural and structural correlates associated with AI and AI with inconsistent condom use.ResultsRDS-adjusted prevalence of AI and AI with inconsistent condom use was high, at 44%[95% confidence interval (95%CI):35-53%]) and 34%[95%CI:26-42%], respectively and did not vary by partner type. HIV prevalence was high in this sample of FSW (70%), but knowledge that AI increases HIV acquisition risk low, with only 10% identifying AI as the riskiest sex act. Those who reported AI were more likely to be better educated (adjusted odds ratio(aOR) = 1.92[95%CI:1.03-3.57]), to have grown up in rural areas (aOR = 1.90[95%CI:1.09-3.32]), have fewer new clients in the past month (aOR = 0.33[95%CI:0.16-0.68]), and for last sex with clients to be condomless (aOR = 2.09[95%CI:1.07-4.08]). Although FSW reporting AI in past month were more likely to have been raped (aOR = 1.95[95%CI:1.05-3.65]) and harassed because of being a sex worker (aOR = 2.09[95%CI:1.16-3.74]), they were also less likely to have ever been blackmailed (aOR = 0.50[95%CI:0.25-0.98]) or been afraid to walk in public places (aOR = 0.46[95%CI:0.25-0.87]). Correlates of AI with inconsistent condom use were similar to those of AI.ConclusionsAI is commonly practised and condom use is inconsistent among Swazi FSW. Sex act data are needed to determine how frequently AI is practiced. Interventions to address barriers to condom use are needed, as are biomedical interventions that reduce acquisition risk during AI.

[This corrects the article DOI: 10.1371/journal.pone.0228849.].

Long-acting injectable (LAI) HIV pre-exposure prophylaxis (PrEP) may mitigate adherence challenges reported by young women in Southern Africa. We assessed preferences for PrEP in public-sector, primary care clinics in Swaziland. Among surveyed respondents, 75% (95% confidence interval = 65-83%) stated preference for LAI over oral PrEP; with no differences by sex, age, or sexual behavior (all P > 0.05). Notably, over 70% (95% confidence interval 58-82%) with current use of oral PrEP also stated preference for LAI PrEP.