Quantifying the impact of cascade inequalities: a modelling study on the prevention impacts of antiretroviral therapy scale-up in Eswatini.

Background: Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95-95-95 targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate additional HIV infections expected in Eswatini if cascade scale-up had not been equal, and under which epidemic conditions these inequalities could have the largest influence. Methods: Drawing on population-level and FSW-specific surveys in Eswatini, we developed a compartmental model of heterosexual HIV transmission which included eight subpopulations and four sexual partnership types. We calibrated the model to stratified HIV prevalence, incidence, and ART cascade data. Taking observed cascade scale-up in Eswatini as the base-case-reaching 95-95-95 in the overall population by 2020-we defined four counterfactual scenarios in which the population overall reached 80-80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60-40-80. We quantified relative additional cumulative HIV infections by 2030 in counterfactual vs base-case scenarios. We further estimated linear effects of viral suppression gap among FSW and clients on additional infections by 2030, plus effect modification by FSW/client population sizes, rates of turnover, and HIV prevalence ratios. Results: Compared with the base-case scenario, leaving behind neither FSW nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 14.9 (10.4, 18.4)% vs 26.3 (19.7, 33.0)% if both were left behind-a 73 (40, 149)% increase. The effect of lower cascade on additional infections was larger for clients vs FSW, and both effects increased with population size and relative HIV incidence. Conclusions: Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade, particularly those that intersect with high transmission risk, could maximize incidence reductions from cascade scale-up.

Uptake of and intention to use oral pre-exposure prophylaxis for HIV among pregnant and post-natal women in Eswatini: a cross-sectional survey.

Introduction: In Eswatini, HIV incidence among women of childbearing age is 1.45%. Eswatini introduced oral pre-exposure prophylaxis (PrEP) for HIV prevention in 2016 and requires that all HIV-negative pregnant and post-natal women (PPW) visiting health care facilities be offered PrEP. Methods: Between September-November 2021, we conducted a survey among HIV-negative PPW from 16 purposively selected healthcare facilities in the Hhohho and Shiselweni regions in Eswatini. We interviewed consenting HIV-negative PPW using a structured questionnaire to collect data on PrEP knowledge, attitudes, intentions, and practices, as well as information on partner HIV status and stigma. Multivariate logistic regression was used to determine predictors of PrEP use and intention, adjusted for significant covariates. Results: Of 1,484 PPW women approached, 1,149 consented and were interviewed, of whom 704 (61.3%) were post-partum and 445 (38.7%) pregnant. The median age was 25 years [Interquartile Range (IQR) = 21-30 years], with 533 (46.4%) 18-24 years old. Among the 1,149 women, 930 (80.7%) had ever heard about PrEP; 635 (55.3%) had knowledge about PrEP; 183 (15.9%) were currently using PrEP; and 285 (24.8%) had ever used PrEP. Increased odds of PrEP use were associated having HIV-positive male partner (aOR:7.76, 95%CI 3.53- 17.04); positive attitudes to PrEP (aOR:1.56, 95%CI: 1.02-2.40); and high self-efficacy (aOR:1.49, 95%CI:1.13-1.98). Among 864 women who never used PrEP, 569 (65.3%) intended to use PrEP in the future. Odds of intention to use PrEP were higher among women with low levels of education (aOR:2.23, 95% CI: 1.32-3.77); who ever heard about PrEP (aOR:1.69, 95%CI: 1.12-2.56); and had high self-efficacy (aOR:1.57, 95%CI: 1.31-1.87). Regarding stigma, among all women, 759 (66%) either agreed or strongly agreed that people would think they have HIV if they were to use PrEP; 658 (57.3%) reported they would be labelled as having multiple sex partners; 468 (40.7%) reported that their partner would think they are having risky sex with other people. Of 102 women who had discontinued PrEP, a majority stopped due to side effects 32 (35.2%). Conclusion: Only about 50% of women had knowledge of PrEP, and PrEP uptake among PPW was low, though intention to use appeared high. More efforts to reduce stigma and promote PrEP use, including adequate information on side effects, are needed.

The relationship between underage initiation of selling sex and depression among female sex workers in Eswatini.

Background: Minors 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. Methods: From 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. Results: Overall, 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 [aOR] 1.70, 95% confidence interval 1.11-2.60). Conclusion: Results highlight the need for trauma-informed and adolescent-friendly mental health services in settings free of stigma toward female sex workers in Eswatini.

'We Should Not Be Quiet but We Should Talk': Qualitative Accounts of Community-Based Communication of HIV Pre-Exposure Prophylaxis.

Community leaders play an important role in the acceptance of public health services, but little is known about their willingness to facilitate HIV pre-exposure prophylaxis (PrEP) roll-out in Eswatini. We conducted in-depth interviews (n = 25) with purposefully selected male and female community leaders in Eswatini. We analysed our data inductively using a thematic analysis approach. Community leaders feel they are important communicators of culturally appropriate PrEP messaging. Our participants described a complex social space within their communities influenced by religion, tradition, values, and HIV stigma. Community leaders use their position to provide leverage for unique, effective, and easily accessible messages and platforms to reach the community in a manner that ensures trust, relatability, familiarity, and shared faith. Community leaders feel that they are trusted and see trust manifesting in the conversations they are able to engage in, and have a reach that extends beyond formal health services. Existing PrEP programming should embed community leader participation in PrEP programming and engage the trust, knowledge, and potential of community leaders to support PrEP uptake and acceptance.

Cultural Repertoires and Situated Selections as an Alternative Framework to Hegemonic Masculinities: Findings From Eswatini.

Since the 1980s studies on men have frequently utilized Connell's framework of hegemonic masculinities. We critically appraise this framework in the context of a population-based HIV pre-exposure prophylaxis study in Eswatini. Our findings highlight that men confidently show variation in their behavior and choices, which manifest across different men and within the same men acting in particular situations and over the life course. This led us to interrogate the hegemonic masculinities framework on the following grounds: Men's choices and behavior do not seem to fit the model of aspiring to a hegemonic ideal; the delineation of masculine traits as hegemonic or subordinate remain vague in terms of "responsibility," "fidelity," and "consideration for others"; the binary gender concept underpinning hegemonic masculinities seems outdated. Building on the work of Hirsch and Kachtan, we propose cultural repertoires as an alternative framework which also bridges the gender divide.

Associations between punitive policies and legal barriers to consensual same-sex sexual acts and HIV among gay men and other men who have sex with men in sub-Saharan Africa: a multicountry, respondent-driven sampling survey.

BACKGROUND: Few assessments of associations between structural-level factors and HIV among gay men and other men who have sex with men (MSM) have been conducted, especially in sub-Saharan Africa. Our objective was to examine HIV testing history, HIV status, and stigmas among MSM living in ten countries with heterogeneous legal environments. METHODS: This study used pooled data from ten country-specific, cross-sectional studies done in 25 sites in Burkina Faso, Cameroon, Côte d'Ivoire, The Gambia, Guinea-Bissau, Nigeria, Senegal, Eswatini, Rwanda, and Togo. MSM were recruited by respondent-driven sampling and were eligible if they met country-specific requirements for age, area of residence, and self reported being assigned male sex at birth and having anal sex with a man in the past 12 months. Policy related to same-sex sexual behaviour for each country was categorised as not criminalised or criminalised. Countries were also categorised on the basis of recent reports of prosecutions related to same-sex sexual acts. Legal barriers were defined as those that legally prevented registration or operation of sexual orientation related civil society organisations (CSOs). Individual data on HIV testing history, HIV status, and stigma were collected via interviewer-administered sociobehavioural questionnaires and HIV testing. Multilevel logistic regression with random intercepts was used to assess the association between policies, recent prosecutions, legal barriers to CSOs, and HIV-related factors with adjusted odds ratios (aORs) and 95% CIs. FINDINGS: Between Aug 3, 2011, and May 27, 2020, we recruited 8047 MSM with a median age of 23 years (IQR 21-27). 4886 (60·7%) lived in countries that criminalise same-sex sexual acts. HIV prevalence among MSM was higher in criminalised settings than non-criminalised settings (aOR 5·15, 95% CI 1·12-23·57); higher in settings with recent prosecutions than in settings without prosecutions (12·06, 7·19-20·25); and higher in settings with barriers to CSOs than without barriers to CSOs (9·83, 2·00-48·30). HIV testing or status awareness was not associated with punitive policies or practices. Stigma was associated with HIV status but did not consistently vary across legal environments. Disparities in HIV prevalence between MSM and other adult men were highest in punitive settings. INTERPRETATION: Structural risks including discriminatory country-level policies, prosecutions, and legal barriers might contribute to higher HIV prevalence among MSM. Taken together, these data highlight the importance of decriminalisation and decreasing enforcement, alongside stigma reduction, as central to effective control for HIV. FUNDING: National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Out-of-pocket Expenses and Time Spent on Clinic Visits Among HIV Pre-exposure Prophylaxis Users and Other Clinic Attendees in Eswatini.

User costs constitute a barrier to the uptake of HIV pre-exposure prophylaxis (PrEP), but their magnitude appears rarely assessed. In this prospective observational study, we assessed self-reported out-of-pocket expenses (OOPE) and time spent on clinic visits during a PrEP demonstration project in Eswatini. At six public primary care clinics, 240 PrEP users and other clinic attendees were interviewed after a clinic visit. Among the 79.2% of clinic attendees reporting any medical OOPE (e.g., expenses for consultations or drugs) and/or non-medical OOPE (e.g., expenses for transport, food, or phone use), the median total OOPE was $1.36 (IQR 0.91-1.96). Non-medical OOPE occurred mostly due to transport expenses. The median travel time for a clinic visit was 1.0 h (IQR 0.67-2.0). The median time spent in the clinic was 2.0 h (IQR 1.15-3.0). The median opportunity cost of a clinic visit was $7.54 (IQR 5.42-11) when valuing time spent on a clinic visit with Eswatini's per-capita gross domestic product. Our findings can guide measures to reduce the user costs of PrEP in Eswatini and other contexts in which oral PrEP is provided through health care facilities.

RESUMEN: Los costes de los usuarios constituyen un obstáculo para la adopción de la profilaxis previa a la exposición al VIH (PrEP), pero su magnitud rara vez se evalúa. En este estudio observacional prospectivo, evaluamos los gastos de bolsillo (OOPE) declarados por los propios usuarios y el tiempo dedicado a las visitas clínicas durante un proyecto de demostración de la PrEP en Eswatini. En seis clínicas públicas de atención primaria, se entrevistó a 240 usuarios de la PrEP y a otros asistentes a la clínica después de una visita a la misma. Entre el 79,2% de los asistentes a las clínicas que declararon algún OOPE médico (por ejemplo, gastos por consultas o medicamentos) y/o OOPE no médico (por ejemplo, gastos de transporte, comida o uso del teléfono), la mediana del OOPE total fue de 1,36 dólares (IQR: 0,91­1,96). Los gastos no médicos se debieron principalmente a los gastos de transporte. La mediana del tiempo de viaje para una visita a la clínica fue de 1,0 horas (IQR 0,67­2,0). La mediana del tiempo empleado en la clínica fue de 2 horas (IQR 1,15­3,0). La mediana del coste de oportunidad de una visita a la clínica fue de 7,65 dólares (IQR 5,55­11) al valorar el tiempo dedicado a una visita a la clínica con el producto interior bruto per cápita de Eswatini. Nuestros resultados pueden orientar las medidas para reducir los costes de uso de la PrEP en Eswatini y en otros contextos en los que se suministra la PrEP oral a través de los centros de salud.

Human resource needs and costs for HIV pre-exposure prophylaxis provision in nurse-led primary care in Eswatini and opportunities for task sharing.

BACKGROUND: The global expansion of HIV pre-exposure prophylaxis (PrEP) includes health systems that face a shortage of skilled health care workers (HCWs). We estimated the human resource needs and costs for providing PrEP in nurse-led primary care clinics in Eswatini. Furthermore, we assessed potential cost savings from task sharing between nurses and other HCW cadres. METHODS: We conducted a time-and-motion and costing study in a PrEP demonstration project between August 2017 and January 2019. A form for recording time and performed activities ("motion") was filled by HCWs of six primary care clinics. To estimate the human resource needs for specific PrEP activities, we allocated recorded times to performed PrEP activities using linear regression with and without adjusting for a workflow interruption, that is, if a client was seen by different HCWs or by the same HCW at different times. We assessed a base case in which a nurse provides all PrEP activities and five task shifting scenarios, of which four include workflow interruptions due to task sharing between different HCW cadres. RESULTS: On average, PrEP initiation required 29 min (95% CI 25-32) of HCW time and PrEP follow-up 16 min (95% CI 14-18). The HCW time cost $4.55 (uncertainty interval [UI] 1.52-9.69) for PrEP initiation and $2.54 (UI 1.07-4.64) for PrEP follow-up when all activities were performed by a nurse. Time costs were $2.30-4.25 (UI 0.62-9.19) for PrEP initiation and $1.06-2.60 (UI 0.30-5.44) for PrEP follow-up when nurses shared tasks with HCWs from lower cadres. Interruptions of the workflow added, on average, 3.4 min (95% CI 0.69-6.0) to the time HCWs needed for a given number of PrEP activities. The cost of an interrupted workflow was estimated at $0.048-0.87 (UI 0.0098-1.63) depending on whose time need increased. CONCLUSIONS: A global shortage of skilled HCWs could slow the expansion of PrEP. Task shifting to lower-cadre HCW in nurse-led PrEP provision can free up nurse time and reduce the cost of PrEP provision even if interruptions associated with task sharing increase the overall human resource need.

Casting a Wide Net: HIV Drug Resistance Monitoring in Pre-Exposure Prophylaxis Seroconverters in the Global Evaluation of Microbicide Sensitivity Project.

BACKGROUND: Evidence of HIV drug resistance (HIVDR) in individuals using oral pre-exposure prophylaxis (PrEP) who acquire HIV is limited to clinical trials and case studies. More data are needed to understand the risk of HIVDR with oral PrEP during PrEP rollout. Mechanisms to collect these data vary, and are dependent on cost, scale of PrEP distribution, and in-country infrastructure for the identification, collection, and testing of samples from PrEP seroconverters. METHODS: The Global Evaluation of Microbicide Sensitivity (GEMS) project, in collaboration with country stakeholders, initiated HIVDR monitoring among new HIV seroconverters with prior PrEP use in Eswatini, Kenya, South Africa, and Zimbabwe. Standalone protocols were developed to assess HIVDR among a national sample of PrEP users. In addition, HIVDR testing was incorporated into existing demonstration projects for key populations. LESSONS LEARNED: Countries are supportive of conducting a time-limited evaluation of HIVDR during the early stages of PrEP rollout. As PrEP rollout expands, the need for long-term HIVDR monitoring with PrEP will need to be balanced with maintaining national HIV drug resistance surveillance for pretreatment and acquired drug resistance. Laboratory capacity is a common obstacle to setting up a monitoring system. CONCLUSIONS: Establishing HIV resistance monitoring within PrEP programs is feasible. Approaches to drug resistance monitoring may evolve as the PrEP programs mature and expand. The methods and implementation support offered by GEMS assisted countries in developing methods to monitor for drug resistance that best fit their PrEP program needs and resources.

PrEP uptake and delivery setting preferences among clients visiting six healthcare facilities in Eswatini.

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.

RESUMEN: 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.

Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data.

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.

The Costs of Creatinine Testing in the Context of a HIV Pre-Exposure Prophylaxis Demonstration Project in Eswatini.

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.

RESUMEN: 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.

PrEP reminds me that I am the one to take responsibility of my life: a qualitative study exploring experiences of and attitudes towards pre-exposure prophylaxis use by women in Eswatini.

BACKGROUND: Pre-exposure-prophylaxis (PrEP) has been heralded for its potential to put women in control of preventing HIV infection, but uptake and continuation rates have been disappointing in high-incidence settings in sub-Saharan Africa. We explored structural and social factors that influenced PrEP use among young women and pregnant or breastfeeding women in rural Eswatini. METHODS: We conducted two in-depth interviews with ten women on PrEP, and one-time in-depth interviews with fourteen women who declined or discontinued PrEP. Interviews covered decision-making processes around PrEP initiation and experiences with pill-taking. In-depth interviews were conducted with nine health workers, covering experiences in delivering PrEP services, and two focus group discussions were held with men to elicit their perceptions of PrEP. Interviews and discussions were audio-recorded, translated, transcribed and analysed thematically, using an inductive approach. RESULTS: PrEP initiation and use were experienced by many women as empowering them to take control of their health and well-being, and stay HIV free, facilitating them to realise their aspirations relating to motherhood and educational attainment. However, the social norms that defined relationship dynamics with partners or family members either undermined or promoted this empowerment potential. In particular, young women were rarely supported by family members to take PrEP unless it was perceived to be for protecting an unborn child. Stigmatisation of pill-taking through its associations with HIV and the burden of daily pill-taking also contributed to PrEP discontinuation. CONCLUSIONS: Unlike many prevention tools, PrEP enabled women to achieve a sense of control over their lives. Nevertheless, women's agency to continue and adhere to PrEP was influenced by social and structural factors including gender norms, family expectations of young women, relationship dynamics and stigma related to HIV. Future interventions should address these barriers to promote PrEP use among sexually-active women.

Qualitative accounts of PrEP discontinuation from the general population 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.

A stepped-wedge randomized trial and qualitative survey of HIV pre-exposure prophylaxis uptake in the Eswatini population.

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.

"It's hard for us men to go to the clinic. We naturally have a fear of hospitals." Men's risk perceptions, experiences and program preferences for PrEP: A mixed methods study in Eswatini.

Few studies on HIV Pre-Exposure Prophylaxis (PrEP) have focused on men who have sex with women. We present findings from a mixed-methods study in Eswatini, the country with the highest HIV prevalence in the world (27%). Our findings are based on risk assessments, in-depth interviews and focus-group discussions which describe men's motivations for taking up or declining PrEP. Quantitatively, men self-reported starting PrEP because they had multiple or sero-discordant partners or did not know the partner's HIV-status. Men's self-perception of risk was echoed in the qualitative data, which revealed that the hope of facilitated sexual performance or relations, a preference for pills over condoms and the desire to protect themselves and others also played a role for men to initiate PrEP. Trust and mistrust and being able or unable to speak about PrEP with partner(s) were further considerations for initiating or declining PrEP. Once on PrEP, men's sexual behavior varied in terms of number of partners and condom use. Men viewed daily pill-taking as an obstacle to starting PrEP. Side-effects were a major reason for men to discontinue PrEP. Men also worried that taking anti-retroviral drugs daily might leave them mistaken for a person living with HIV, and viewed clinic-based PrEP education and initiation processes as a further obstacle. Given that men comprise only 29% of all PrEP users in Eswatini, barriers to men's uptake of PrEP will need to be addressed, in terms of more male-friendly services as well as trialing community-based PrEP education and service delivery.

High HIV Prevalence and Low HIV-Service Engagement Among Young Women Who Sell Sex: A Pooled Analysis Across 9 Sub-Saharan African Countries.

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.

Correction: Prevalence and correlates of anal intercourse among female sex workers in eSwatini.

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

Modelling impact and cost-effectiveness of oral pre-exposure prophylaxis in 13 low-resource countries.

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.

Prevalence and correlates of anal intercourse among female sex workers in eSwatini.

INTRODUCTION: As 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. METHODS: Using 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. RESULTS: RDS-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. CONCLUSIONS: AI 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.