Prevalence and risk of burnout among HIV service providers in South Africa and Zambia: findings from the HPTN 071 (PopART) trial.

BACKGROUND: In the high disease burden and resource-constrained contexts of sub-Saharan Africa (SSA), health workers experience a range of psychosocial stressors that leave them vulnerable to developing burnout, which can reduce service quality and negatively impact their own health and wellbeing. As universal testing and treatment (UTT) for HIV scales up across SSA, we sought to understand the implications of this human resource-intensive approach to HIV prevention to inform decision-making about health workforce staffing and support needs. METHODS: Using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), we assessed the prevalence of three domains of burnout-emotional exhaustion, depersonalization, and personal accomplishment-among three cadres of health workers delivering health services in areas receiving a UTT intervention in Zambia and South Africa. These cadres included health facility workers (n = 478), community health workers (n = 159), and a study-specific cadre of community HIV care providers (n = 529). We used linear regression to assess risk factors associated with emotional exhaustion, the only domain with sufficient variation in our sample. RESULTS: The MBI-HSS was completed by 1499/2153 eligible participants (69.6% response rate). Less than 1% of health workers met Maslach's definition for burnout. All groups of health workers reported lower levels of emotional exhaustion than found in previous studies of this type (mean score scores ranged from 10.7 to 15.4 out of 54 across health cadres). Higher emotional exhaustion was associated with higher educational attainment (ßadj = 2.24, 95% CI 0.76 to 3.72), greater years providing HIV services (ßadj = 0.20, 95% CI 0.03 to 0.36), and testing negative for HIV at last HIV test (ßadj = - 3.88 - 95% CI 5.69 to - 2.07). Working as a CHW was significantly associated with lower emotional exhaustion (ßadj = - 2.52, 95% CI - 4.69 to - 0.35). Among all health workers, irrespective of HIV status, witnessing stigmatizing behaviors towards people living with HIV among their co-workers was associated with significantly increased emotional exhaustion (ßadj = 3.38, 95% CI 1.99 to 4.76). CONCLUSIONS: The low level of burnout detected among health workers is reassuring. However, it remains important to assess how UTT may affect levels of emotional exhaustion among health workers over time, particularly in the context of emerging global pandemics, as burnout may impact the quality of HIV services they provide and their own mental health and wellbeing. Interventions to reduce HIV stigma in health facilities may protect against emotional exhaustion among health workers, as well as interventions to increase mindfulness and resilience among health workers at risk of burnout. Trial registration ClinicalTrials.gov number: NCT01900977.

Effect of Universal Testing and Treatment on HIV Incidence - HPTN 071 (PopART).

BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.).

Experiences and lessons learned from the real-world implementation of an HIV recent infection testing algorithm in three routine service-delivery settings in Kenya and Zimbabwe.

INTRODUCTION: Testing for recent HIV infection can distinguish recently acquired infection from long-standing infections. Given current interest in the implementation of recent infection testing algorithms (RITA), we report our experiences in implementing a RITA in three pilot studies and highlight important issues to consider when conducting recency testing in routine settings. METHODS: We applied a RITA, incorporating a limited antigen (LAg) avidity assay, in different routine HIV service-delivery settings in 2018: antenatal care clinics in Siaya County, Kenya, HIV testing and counselling facilities in Nairobi, Kenya, and female sex workers clinics in Zimbabwe. Discussions were conducted with study coordinators, laboratory leads, and facility-based stakeholders to evaluate experiences and lessons learned in relation to implementing recency testing. RESULTS: In Siaya County 10/426 (2.3%) of women testing HIV positive were classified as recent, compared to 46/530 (8.7%) of women and men in Nairobi and 33/313 (10.5%) of female sex workers in Zimbabwe. Across the study setting, we observed differences in acceptance, transport and storage of dried blood spot (DBS) or venous blood samples. For example, the acceptance rate when testing venous blood was 11% lower than when using DBS. Integrating our study into existing services ensured a quick start of the study and kept the amount of additional resources required low. From a laboratory perspective, the LAg avidity assay was initially difficult to operationalise, but developing a network of laboratories and experts to work together helped to improve this. A challenge that was not overcome was the returning of RITA test results to clients. This was due to delays in laboratory testing, the need for multiple test results to satisfy the RITA, difficulties in aligning clinic visits, and participants opting not to return for test results. CONCLUSION: We completed three pilot studies using HIV recency testing based on a RITA in Kenya and Zimbabwe. The main lessons we learned were related to sample collection and handling, LAg avidity assay performance, integration into existing services and returning of test results to participants. Our real-world experience could provide helpful guidance to people currently working on the implementation of HIV recency testing in sub-Saharan Africa.

Universal HIV testing and treatment and HIV stigma reduction: a comparative thematic analysis of qualitative data from the HPTN 071 (PopART) trial in South Africa and Zambia.

Despite continued development of effective HIV treatment, expanded access to care and advances in prevention modalities, HIV-related stigma persists. We examine how, in the context of a universal HIV-testing and treatment trial in South Africa and Zambia, increased availability of HIV services influenced conceptualisations of HIV. Using qualitative data, we explore people's stigma-related experiences of living in 'intervention' and 'control' study communities. We conducted exploratory data analysis from a qualitative cohort of 150 households in 13 study communities, collected between 2016 and 2018. We found that increased availability of HIV-testing services influenced conceptualisations of HIV as normative (non-exceptional) and the visibility of people living with HIV (PLHIV) in household and community spaces impacted opportunities for stigma. There was a shift in community narratives towards individual responsibility to take up (assumingly) widely available service - for PLHIV to take care of their own health and to prevent onward transmission. Based on empirical data, we show that, despite a growing acceptance of HIV-related testing services, anticipated stigma persists through the mechanism of shifting responsibilisation. To mitigate the responsibilisation of PLHIV, heath implementers need to adapt anti-stigma messaging and especially focus on anticipated stigma.

Association between HIV stigma and antiretroviral therapy adherence among adults living with HIV: baseline findings from the HPTN 071 (PopART) trial in Zambia and South Africa.

OBJECTIVES: Adherence to antiretroviral therapy (ART) leads to viral suppression for people living with HIV (PLHIV) and is critical for both individual health and reducing onward HIV transmission. HIV stigma is a risk factor that can undermine adherence. We explored the association between HIV stigma and self-reported ART adherence among PLHIV in 21 communities in the HPTN 071 (PopART) trial in Zambia and the Western Cape of South Africa. METHODS: We conducted a cross-sectional analysis of baseline data collected between 2013 and 2015, before the roll-out of trial interventions. Questionnaires were conducted, and consenting participants provided a blood sample for HIV testing. Poor adherence was defined as self-report of not currently taking ART, missing pills over the previous 7 days or stopping treatment in the previous 12 months. Stigma was categorised into three domains: community, health setting and internalised stigma. Multivariable logistic regression was used for analysis. RESULTS: Among 2020 PLHIV self-reporting ever taking ART, 1888 (93%) were included in multivariable analysis. Poor ART adherence was reported by 15.8% (n = 320) of participants, and 25.7% (n = 519) reported experiencing community stigma, 21.5% (n = 434) internalised stigma, and 5.7% (n = 152) health setting stigma. PLHIV who self-reported previous experiences of community and internalised stigma more commonly reported poor ART adherence than those who did not (aOR 1.63, 95% CI 1.21 -2.19, P = 0.001 and aOR 1.31, 95% CI 0.96-1.79, P = 0.09). CONCLUSIONS: HIV stigma was associated with poor ART adherence. Roll-out of universal treatment will see an increasingly high proportion of PLHIV initiated on ART. Addressing HIV stigma could make an important contribution to supporting lifelong ART adherence.

OBJECTIFS: L'adhésion à la thérapie antirétrovirale (ART) conduit à la suppression virale pour les personnes vivant avec le VIH (PVVIH) et est essentielle à la fois pour la santé individuelle et pour réduire la transmission du VIH. La stigmatisation du VIH est un facteur de risque qui peut compromettre l'adhésion. Nous avons exploré l'association entre la stigmatisation du VIH et l'adhésion autodéclarée à l'ART chez les PVVIH dans 21 communautés dans l'essai HPTN 071 (PopART) en Zambie et dans le Western Cape en Afrique du Sud. MÉTHODES: Nous avons effectué une analyse transversale des données de base collectées entre 2013-2015, avant le déploiement des interventions d'essai. Des questionnaires ont été réalisés et les participants consentants ont fourni un échantillon de sang pour le dépistage du VIH. Une mauvaise adhésion a été définie comme l'autodéclaration de ne pas prendre actuellement l'ART, d'omettre des comprimés au cours des 7 jours précédents ou d'arrêter le traitement au cours des 12 mois précédents. La stigmatisation a été classée en trois domaines: communautaire, en milieu de santé et stigmatisation intériorisée. Une régression logistique multivariée a été utilisée pour l'analyse. RÉSULTATS: Parmi les 2.020 PVVIH autodéclarant avoir déjà pris un ART, 1.888 (93%) ont été inclus dans l'analyse multivariée. Une mauvaise adhésion à l'ART a été signalée par 15,8% (n = 320) des participants, 25,7% (n = 519) ont déclaré avoir subi une stigmatisation communautaire, 21,5% (n = 434) une stigmatisation internalisée et 5,7% (n = 152) une stigmatisation en milieu de santé. Les PVVIH qui ont auto-déclaré des expériences antérieures de stigmatisation communautaire et intériorisée ont plus souvent rapporté une mauvaise adhésion à l'ART que ceux qui ne l'ont pas fait (aOR 1,63 ; IC95%: 1,21-2,19 ; P = 0,001 et aOR 1,31 ; IC95%: 0,96-1,79 ; P = 0,09). CONCLUSIONS: La stigmatisation du VIH était associée à une mauvaise adhésion à l'ART. Le déploiement du traitement universel verra une proportion de plus en plus élevée de PVVIH initiées à l'ART. Lutter contre la stigmatisation du VIH pourrait apporter une contribution importante au soutien de l'adhésion à l'ART au cours de la vie. NUMÉRO D'ESSAI CLINIQUE: NCT01900977.

Exploring the Association Between Mobility and Access to HIV Services Among Female Sex Workers in Zimbabwe.

Female sex workers (FSW) face structural barriers to HIV-service access, however the effect of their mobility is uncertain. Using cross-sectional data from 2839 FSW in 14 sites in Zimbabwe, we explored the association between mobility (number of trips, distance, duration) in the past 12 months and five HIV-service-access outcomes: exposure to community mobilisation, clinic attendance, HIV testing, antiretroviral treatment initiation, and viral suppression (< 1000 copies per mL). We used modified-Poisson regression, and natural-effects models to estimate how the effect of trip frequency was mediated by distance and duration away. Each additional trip in 12 months was associated with increased community-mobilisation-event attendance (adjusted RR 1.08, 95% CI 1.04-1.12) and attending clinic two-or-more times (adjusted RR 1.02, 95% CI 1.00-1.05). There was little evidence of any other associations, or of mediation. Our findings are consistent with literature that found the effects of mobility to vary by context and outcome. This is the first study to consider many FSW-mobility and HIV-service-access measures together. Future research on mobility and health-related behaviour should use a spectrum of measures.

Stigma and HIV service access among transfeminine and gender diverse women in South Africa - a narrative analysis of longitudinal qualitative data from the HPTN 071 (PopART) trial.

BACKGROUND: Transgender women have a disproportionately high HIV prevalence compared to cisgender women and men who have sex with men, which puts them at risk of HIV-related stigma (Baral SD et al., Lancet Infect Dis, 13;3, 2013). People whose gender identities are in tension with dominant social norms (including transgender women) often also experience gender identity-related stigma. There has been increasing attention to transgender people in HIV research and interventions. However, very little research has been done in sub-Saharan African countries. METHODS: We conducted a qualitative cohort study which included eight transfeminine and/or gender diverse women (four living with HIV) in Western Cape, South Africa, for a follow-up period of 12-18 months. Using a narrative analysis approach, we set out to understand how transfeminine and gender diverse participants in the cohort anticipated, experienced and internalised HIV stigma and gender identity stigma, and how these stigmas affected HIV service access. RESULT: We found that participants reported anticipated, experienced, and internalised stigma relating both to their gender identity and to living with HIV. Participants reported inconsistent uptake of antiretroviral therapy (ART) services (including ART initiation and adherence) that they linked to stigma. We also found that gender diverse women and transfeminine women are challenged with other stigmatising social identities, like being a sex worker, drug user and/or a man (or assigned male sex at birth) who have sex with men (MSM). We use the terms 'transfeminine' and 'gender diverse' as terms that are inclusive of gender variant people who were all assigned male sex at birth and identify as women in some or all aspects of their lives. The persons in our study also showed gender identifications that were fluid and sometimes varied in different contexts and situations, therefore gender identity and sexual identity were often conflated for these individuals. Participants managed high levels of reported stigma by drawing on social support networks like families, friends and peers. CONCLUSION: Our study provides exploratory work on how stigma may affect HIV services uptake amongst gender diverse women and transfeminine women in South Africa. We recommend future studies to further explore the unique HIV risks of gender diverse individuals. TRIAL REGISTRATION: DOH-27-0513-4253 .

Friendships Among Young South African Women, Sexual Behaviours and Connections to Sexual Partners (HPTN 068).

Friends could be influential on young women's sexual health via influences on sexual behaviours and as connections to sexual partners, but are understudied in sub-Saharan Africa. We cross-sectionally surveyed 2326 13-20 year-old young women eligible for grades 8-11 in rural South Africa about their sexual behaviour and up to three sexual partners. Participants each described five specific but unidentified friends and the relationships between them in an 'egocentric' network analysis design. We used logistic regression to investigate associations between friendship characteristics and participants' reports of ever having had sex (n = 2326) and recent condom use (n = 457). We used linear regression with random effects by participant to investigate friendship characteristics and age differences with sexual partners (n = 633 participants, 1051 partners). We found that it was common for friends to introduce young women to those who later became sexual partners, and having older friends was associated with having older sexual partners, (increase of 0.37 years per friend at least 1 year older, 95% CI 0.21-0.52, adjusted). Young women were more likely to report ever having had sex when more friends were perceived to be sexually active (adjusted OR 1.85, 95% CI 1.72-2.01 per friend) and when they discussed sex, condoms and HIV with friends. Perception of friends' condom use was not associated with participants' reported condom use. While this study is preliminary and unique in this population and further research should be conducted, social connections between friends and sexual partners and perceptions of friend sexual behaviours could be considered in the design of sexual health interventions for young women in South Africa.

Application of an HIV Prevention Cascade to Identify Gaps in Increasing Coverage of Voluntary Medical Male Circumcision Services in 42 Rural Zambian Communities.

Increased coverage of voluntary medical male circumcision (VMMC) is needed in countries with high HIV prevalence. We applied an HIV-prevention cascade to identify gaps in male circumcision coverage in Zambia. We used survey data collected in 2013 and 2014/15 to describe circumcision coverage at each time-point, and prevalence of variables related to demand for and supply of VMMC. We explored whether circumcision coverage in 2014/15 was associated with demand and supply among uncircumcised men in 2013. Results show that circumcision coverage was 11.5% in 2013 and 18.0% in 2014/15. Levels of having heard of circumcision and agreeing with prevention benefits was similar at both time-points (79.8% vs 83.2%, and 49.7% vs 50.7%, respectively). In 2013, 39.3% of men perceived services to be available compared to 54.7% in 2014/15. Levels of having heard of circumcision in 2013 was correlated with and higher perceived service availability associated with coverage in 2014/15. VMMC coverage was low in these study sites. Knowledge of prevention tools and of service availability are necessary to increase coverage but alone are insufficient.

Changes Over Time in HIV Prevalence and Sexual Behaviour Among Young Female Sex-Workers in 14 Sites in Zimbabwe, 2013-2016.

Young female sex-workers (FSW) aged 18-24 are at high risk of HIV due to high numbers of sexual partners, difficulty negotiating condom use, increased risk of gender-based violence, and limited access to services. Here we describe changes in sexual behaviours among young FSW across Zimbabwe between 2013 and 2016, and risk factors for prevalent HIV in 2013 and 2016. FSW ≥ 18 years were recruited using respondent-driven sampling in 14 sites across Zimbabwe in 2013 and 2016 as part of the SAPPH-IRe trial. We collected data on socio-demographics and sexual behaviour and offered HIV testing. Statistical analyses were RDS-II weighted. Characteristics of young FSW aged 18-24 were described, stratified by age. Logistic regression was used to assess difference in sexual behaviours by reported HIV status between 2013 and 2016, and to explore associations with prevalent HIV in 2013 and 2016. 656 young FSW were recruited in 2013 and 503 in 2016. Characteristics of young FSW were similar across both surveys. HIV prevalence was similar at both time points (35% vs 36%) and rose steeply with age. Compared to young FSW in 2013, reported condom-less sex with a steady partner and condom-less sex with clients was higher in 2016 among women self-reporting HIV negative status (OR = 6.41; 95%CI: 3.40-12.09; P<0.001) and (OR = 1.69; 95%CI: 1.14-2.51, P = 0.008), respectively, but not among young FSW self-reporting HIV positive status (OR = 2.35; 95%CI: 0.57-9.76; P = 0.236) and (OR = 1.87; 95%CI: 0.74-4.74; P = 0.186). After adjusting for age in 2016, young FSW who had ever been married had increased odds of testing HIV positive (OR = 1.88; 95% CI 1.04-3.39; P = 0.036) compared with those who had never married. Young FSW who completed secondary education or higher were less likely to test HIV positive (OR = 0.41; 95% CI 0.20-0.83; P = 0.012) compared with those with primary education or less. Young FSW remain at very high risk of HIV. Strategies to identify young FSW when they first start selling and refer them into services that address their economic, social and sexual vulnerabilities are critical.

Sexuality, fertility and family planning characteristics of married women aged 15 to 19 years in Ethiopia, Nigeria and Tanzania: a comparative analysis of cross-sectional data.

BACKGROUND: Adolescents 360 (A360) is an initiative being rolled out across Ethiopia, Nigeria and Tanzania with the aim of increasing uptake of voluntary modern contraception among sexually active women aged 15 to 19 years. Using evaluation baseline survey data, we described key sexuality, fertility and contraceptive use characteristics of married women aged 15 to 19 years living in three sub-national settings. METHODS: Cross-sectional baseline surveys of married women aged 15 to 19 years were conducted in Oromia (Ethiopia), Nasarawa (Northern Nigeria), and Mwanza (Tanzania) between August 2017 and February 2018. We also interviewed the husbands of a sub-group of married respondents to measure spousal acceptance and support for adolescent women to use modern contraception. A clustered sampling design was used in all three countries. We produced descriptive statistics on the socio-demographic and sexual and reproductive health characteristics of married women aged 15 to 19 years by study setting. RESULTS: In Oromia, Nasarawa and Mwanza, 31.4% (327/1198), 27.4% (1321/4816) and 7.5% (15/201) of married women surveyed had no education, and 68.3, 81.3 and 83.1% had ever been pregnant, respectively. Unmet need for modern contraception was 20.5, 21.9 and 32.0% in married women in Oromia, Nasarawa and Mwanza, made up almost entirely of unmet need for spacing. The vast majority of married women surveyed in Oromia (89.1%) and Mwanza (90.1%) had seen or heard about contraception in the last 12 months, compared to 30.1% of those surveyed in Nasarawa. Modern contraceptive prevalence (mCPR) was highest in married women aged 15 to 19 years in Oromia (47.2%), followed by Mwanza (19.4%) and Nasarawa (8.7%). Of those using a modern method of contraception in Oromia, 93.4% were using injectables or long-acting methods, compared to 49.4% in Nasarawa and 69.6% in Mwanza. CONCLUSIONS: Overall, unmet need for modern contraception is high among married women aged 15 to 19 years across the three settings. mCPR for married women aged 15 to 19 years is low in Nasarawa and Mwanza. Ultimately, no single intervention will suit all situations, but improving the quality, analyses and utilisation of subnational data can help decision-makers design more context specific interventions.

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

Background: Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. Methods: This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Results: Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/µL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Conclusions: Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

Estimating Sizes of Key Populations at the National Level: Considerations for Study Design and Analysis.

BACKGROUND: National estimates of the sizes of key populations, including female sex workers, men who have sex with men, and transgender women are critical to inform national and international responses to the HIV pandemic. However, epidemiologic studies typically provide size estimates for only limited high priority geographic areas. This article illustrates a two-stage approach to obtain a national key population size estimate in the Dominican Republic using available estimates and publicly available contextual information. METHODS: Available estimates of key population size in priority areas were augmented with targeted additional data collection in other areas. To combine information from data collected at each stage, we used statistical methods for handling missing data, including inverse probability weights, multiple imputation, and augmented inverse probability weights. RESULTS: Using the augmented inverse probability weighting approach, which provides some protection against parametric model misspecification, we estimated that 3.7% (95% CI = 2.9, 4.7) of the total population of women in the Dominican Republic between the ages of 15 and 49 years were engaged in sex work, 1.2% (95% CI = 1.1, 1.3) of men aged 15-49 had sex with other men, and 0.19% (95% CI = 0.17, 0.21) of people assigned the male sex at birth were transgender. CONCLUSIONS: Viewing the size estimation of key populations as a missing data problem provides a framework for articulating and evaluating the assumptions necessary to obtain a national size estimate. In addition, this paradigm allows use of methods for missing data familiar to epidemiologists.

Evaluating the impact of DREAMS on HIV incidence among young women who sell sex: protocol for a non-randomised study in Zimbabwe.

BACKGROUND: "Determined, Resilient, AIDS-free, Mentored and Safe" (DREAMS) is a package of biomedical, social and economic interventions offered to adolescent girls and young women aged 10-24 years with the aim of reducing HIV incidence. In four of the six DREAMS districts in Zimbabwe, DREAMS includes an offer of oral pre-exposure prophylaxis (DREAMS+PrEP), alongside interventions to support demand and adherence, to women aged 18-24 who are at highest risk of HIV infection, including young women who sell sex (YWSS). This evaluation study addresses the question: does the delivery of DREAMS+PrEP through various providers reduce HIV incidence among YWSS Zimbabwe? We describe our approach to designing a rigorous study to assess whether DREAMS+PrEP had an impact on HIV incidence. METHODS: The study design needed to account for the fact that: 1) DREAMS+PrEP was non-randomly allocated; 2) there is no sampling frame for the target population for the evaluation; 3) there are a small number of DREAMS districts (N = 6), and 4) DREAMS+PrEP is being implemented by various providers. The study will use a cohort analysis approach to compare HIV incidence among YWSS in two DREAMS+PrEP districts to HIV incidence among YWSS in non-DREAMS comparison sites. YWSS will be referred to services and recruited into the cohort through a network-based (respondent-driven) recruitment strategy, and followed-up 12- and 24-months after enrolment. Women will be asked to complete a questionnaire and offered HIV testing. Additional complications of this study include identifying comparable populations of YWSS in the DREAMS+PrEP and non-DREAMS comparison sites, and retention of YWSS over the 24-month period. The primary outcome is HIV incidence among YWSS HIV-negative at study enrolment measured by repeat, rapid HIV testing over 24-months. Inference will be based on plausibility that DREAMS+PrEP had an impact on HIV incidence. A process evaluation will be conducted to understand intervention implementation, and document any contextual factors determining the success or failure of intervention delivery. DISCUSSION: HIV prevention products of known efficacy are available. Innovative studies are needed to provide evidence of how to optimise product use through combination interventions to achieve population impact within different contexts. We describe the design of such a study.

Evaluating the impact of the DREAMS partnership to reduce HIV incidence among adolescent girls and young women in four settings: a study protocol.

BACKGROUND: HIV risk remains unacceptably high among adolescent girls and young women (AGYW) in southern and eastern Africa, reflecting structural and social inequities that drive new infections. In 2015, PEPFAR (the United States President's Emergency Plan for AIDS Relief) with private-sector partners launched the DREAMS Partnership, an ambitious package of interventions in 10 sub-Saharan African countries. DREAMS aims to reduce HIV incidence by 40% among AGYW over two years by addressing multiple causes of AGYW vulnerability. This protocol outlines an impact evaluation of DREAMS in four settings. METHODS: To achieve an impact evaluation that is credible and timely, we describe a mix of methods that build on longitudinal data available in existing surveillance sites prior to DREAMS roll-out. In three long-running surveillance sites (in rural and urban Kenya and rural South Africa), the evaluation will measure: (1) population-level changes over time in HIV incidence and socio-economic, behavioural and health outcomes among AGYW and young men (before, during, after DREAMS); and (2) causal pathways linking uptake of DREAMS interventions to 'mediators' of change such as empowerment, through to behavioural and health outcomes, using nested cohort studies with samples of ~ 1000-1500 AGYW selected randomly from the general population and followed for two years. In Zimbabwe, where DREAMS includes an offer of pre-exposure HIV prophylaxis (PrEP), cohorts of young women who sell sex will be followed for two years to measure the impact of 'DREAMS+PrEP' on HIV incidence among young women at highest risk of HIV. In all four settings, process evaluation and qualitative studies will monitor the delivery and context of DREAMS implementation. The primary evaluation outcome is HIV incidence, and secondary outcomes include indicators of sexual behavior change, and social and biological protection. DISCUSSION: DREAMS is, to date, the most ambitious effort to scale-up combinations or 'packages' of multi-sectoral interventions for HIV prevention. Evidence of its effectiveness in reducing HIV incidence among AGYW, and demonstrating which aspects of the lives of AGYW were changed, will offer valuable lessons for replication.

Bias and inference from misspecified mixed-effect models in stepped wedge trial analysis.

Many stepped wedge trials (SWTs) are analysed by using a mixed-effect model with a random intercept and fixed effects for the intervention and time periods (referred to here as the standard model). However, it is not known whether this model is robust to misspecification. We simulated SWTs with three groups of clusters and two time periods; one group received the intervention during the first period and two groups in the second period. We simulated period and intervention effects that were either common-to-all or varied-between clusters. Data were analysed with the standard model or with additional random effects for period effect or intervention effect. In a second simulation study, we explored the weight given to within-cluster comparisons by simulating a larger intervention effect in the group of the trial that experienced both the control and intervention conditions and applying the three analysis models described previously. Across 500 simulations, we computed bias and confidence interval coverage of the estimated intervention effect. We found up to 50% bias in intervention effect estimates when period or intervention effects varied between clusters and were treated as fixed effects in the analysis. All misspecified models showed undercoverage of 95% confidence intervals, particularly the standard model. A large weight was given to within-cluster comparisons in the standard model. In the SWTs simulated here, mixed-effect models were highly sensitive to departures from the model assumptions, which can be explained by the high dependence on within-cluster comparisons. Trialists should consider including a random effect for time period in their SWT analysis model. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Self-care interventions for women's health and well-being.

The human right to health is universal and non-exclusionary, supporting health in full, and for all. Despite advances in health systems globally, 3.6 billion people lack access to essential health services. Women and girls are disadvantaged when it comes to benefiting from quality health services, owing to social norms, unequal power in relationships, lack of consideration beyond their reproductive roles and poverty. Self-care interventions, including medicines and diagnostics, which offer an additional option to facility-based care, can improve the autonomy and agency of women in managing their own health. However, tackling challenges such as stigma is essential to avoid scenarios in which self-care interventions provide more choice for those who already benefit from access to quality healthcare, and leave behind those with the greatest need. This Perspective explores the opportunities that self-care interventions offer to advance the health and well-being of women with an approach grounded in human rights, gender equality and equity.

Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.

INTRODUCTION: "Programme science" deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: (1) feasible to undertake, (2) useful, (3) rigorous, (4) real-world-relevant, (5) informative, and undertaken by (6) equitable partnerships. The acronym "FURRIE" is proposed to describe this set of six challenges. This paper discusses selected HIV/STI (sexually transmitted infection) programme science case studies to illustrate how programme science rises to the FURRIE challenges. DISCUSSION: One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, these data can be augmented through methods that reach potential clients of services who have not accessed services or been lost to follow-up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigour by limiting bias and confounding in the real-world context of programme science studies requires methodological innovation. Striving for scientific rigour can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the "real-world." Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. CONCLUSIONS: Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field.

Use of routinely collected blood donation data for expanded HIV and Syphilis surveillance in Blantyre district, Malawi.

The World Health Organization recommends that all blood donations be screened for transfusion transmissible infections; these data are currently not incorporated into national disease surveillance efforts. We set out to use routinely collected data from blood donors in Blantyre district, Malawi to explore HIV and syphilis prevalence and identify sero-conversions among repeat donors. We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service from 2015 to 2021. All blood donations were routinely screened for HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative on their last donation. A total of 23,280 donations from 5,051 donors were recorded, with a median frequency of donations of 3 (IQR:2-6). Most donors were male (4,294; 85%) and students (3,262; 64.6%). Prevalence of HIV at first donation was 1.0% (52/5,051) and prevalence of syphilis was 1.6% (80/5,051); 52 HIV sero-conversions and 126 syphilis sero-conversions were identified, indicating an incidence rate per 1,000 person-years of 5.9 (95% CI: 4.7, 7.4) and 13.3 (95% CI:11.4, 15.4) respectively. Students had a lower prevalence of HIV and syphilis but higher risk of syphilis seroconversion. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify relatively high rates of undiagnosed HIV and syphilis infections among donors. Routinely collected data from national blood donation services may be used to better understand local HIV and syphilis epidemiology, with the potential to enhance disease surveillance systems. These findings may be used to identify priority prevention areas and populations in Blantyre district that can inform targeted interventions for improved disease prevention, testing and treatment.