Advancing Adolescent HIV Prevention and Care Through Implementation Science: An Agenda for Combating the Global AIDS Epidemic in Sub-Saharan Africa.

AIDS continues to be a major driver of adolescent mortality in Sub-Saharan Africa. Despite evidence of efficacy in this population, many efforts to address adolescent HIV have had limited impact across the region because of difficulty with implementation. The field of implementation science holds promise for addressing these challenges. The Fogarty-led Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) creates a platform for bidirectional learning between researchers and the users of research evidence that promotes the use of implementation science to strengthen adolescent HIV prevention and care across Africa. The unique contributions of AHISA are reflected in this supplement's articles which represent the collective learning of the Alliance; illustrate the value of implementation science in the context of adolescent HIV; and identify critical research gaps that should be addressed by implementation science in the future.

Impact of Vaccination and Nonpharmaceutical Interventions With Possible COVID-19 Viral Evolutions Using an Agent-Based Simulation.

Introduction: The COVID-19 pandemic continues with highly contagious variants and waning immunity. As the virus keeps evolving to be more infectious and immune evasive, some question whether the COVID-19 pandemic can be managed through sustainable public health measures. Methods: We developed an agent-based simulation to explore the impact of COVID-19 mutations, periodic vaccinations, and nonpharmaceutical interventions on reducing COVID-19 deaths. The model is calibrated to the greater Seattle area by observing local epidemic data. We perform scenario analyses on viral mutations that change infectiousness, disease severity, and immune evasiveness from previous infections and vaccination every 6 months. The simulation is run until the end of year 2023. Results: Variants with increased infectivity or increased immune evasion dominate previous strains. With enhanced immune protection from a pancoronavirus vaccine, the most optimistic periodic vaccination rate reduces average total deaths by 44.6% compared with the most pessimistic periodic vaccination rate. A strict threshold nonpharmaceutical intervention policy reduces average total deaths by 71.3% compared with an open society, whereas a moderate nonpharmaceutical intervention policy results in a 33.6% reduction. Conclusions: Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic.

The utility of a composite biological endpoint in HIV/STI prevention trials.

A human immunodeficiency virus (HIV) as a biological endpoint in HIV prevention trials may not be feasible, so investigators have used surrogate biological outcomes. In a multisite trial, the epidemiology of STIs may be different across sites and preclude using one STI as the outcome. This study explored using a composite STI outcome to address that problem. The combined biological endpoint was the incidence of any of six new STIs (chlamydia, gonorrhea, trichomonas (women only), syphilis, herpes simplex virus type 2 infection and HIV) during a 24-month follow up period. We investigated how a composite STI outcome would perform compared to single and dual STI outcomes under various conditions. We simulated outcomes for four populations that represented a wide range of sex and age distributions, and STI prevalences. The simulations demonstrated that a combined biologic outcome was superior to single and dual STI outcomes in assessing intervention effects in 82 % of the cases. A composite biological outcome was effective in detecting intervention effects and might allow more investigations to incorporate multiple biological outcomes in the assessment of behavioral intervention trials for HIV prevention.

Trends in the Use of Face Coverings in Publicly Accessible Spaces During the COVID-19 Pandemic, King County, Washington, November 2020-May 2021.

OBJECTIVES: Appropriate face covering use at public venues can help mitigate the transmission of SARS-CoV-2 in the absence of widespread vaccination and provide protection when viral variants become more infectious. The objective of this study was to evaluate compliance with a statewide face mask mandate by examining trends in face covering use in publicly accessible spaces in King County, Washington. METHODS: From November 27, 2020, through May 11, 2021, we conducted a repeated cross-sectional observational study of face covering use across publicly accessible venues (eg, grocery and convenience stores, airport, transit center, post office). Trained observers recorded perceived sex, estimated age group, and face covering use. We calculated estimates of overall face covering use and prevalence ratios (PRs) with 95% CIs. RESULTS: We observed 9865 people in 53 unique venues during 229 observation intervals during 6 observation periods. Correct face covering use was 87.2% overall and lowest at semi-outdoor venues such as transit hubs (78.1%) and the pick-up curb of Seattle-Tacoma International Airport (69.0%). Correct face covering use was lowest among men (PR = 1.42; 95% CI, 1.27-1.58) and among people aged 2-11 years (PR = 2.74; 95% CI, 2.37-3.17) and 12-17 years (PR = 1.36; 95% CI, 1.07-1.72). Compliance declined among adults aged ≥60 years and among younger age groups before vaccine eligibility. CONCLUSIONS: Overall compliance with the statewide face mask mandate in King County was high. Layered mitigation strategies, including but not limited to the use of face coverings, and methods to assess adherence to them are crucial to preventing SARS-CoV-2 transmission.

Combination HIV prevention: significance, challenges, and opportunities.

No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop "prevention packages" that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

COVID-19 Pandemic Response Simulation in a Large City: Impact of Nonpharmaceutical Interventions on Reopening Society.

As the novel coronavirus (COVID-19) pandemic continues to expand, policymakers are striving to balance the combinations of nonpharmaceutical interventions (NPIs) to keep people safe and minimize social disruptions. We developed and calibrated an agent-based simulation to model COVID-19 outbreaks in the greater Seattle area. The model simulated NPIs, including social distancing, face mask use, school closure, testing, and contact tracing with variable compliance and effectiveness to identify optimal NPI combinations that can control the spread of the virus in a large urban area. Results highlight the importance of at least 75% face mask use to relax social distancing and school closure measures while keeping infections low. It is important to relax NPIs cautiously during vaccine rollout in 2021.

Opportunities and Challenges in North-South and South-South Global Health Collaborations During the COVID-19 Pandemic: The AFREhealth-CUGH Experience (as Reported at the CUGH 2021 Satellite Meeting).

Sustainable and equitable partnerships and collaborations between the Global North and Global South (as well as within the Global South) have been aspirations (if seldom achieved) of the "global health" endeavor over the past couple of decades. The COVID-19 pandemic led to global lockdowns that disrupted international travel and severely challenged these partnerships, providing a critical space for self-reflection on global health as a discipline. One major global north-south partnership is that between the African Forum for Research and Education in Health (AFREhealth) and the Consortium of Universities for Global Health (CUGH). This article reports on a recent Satellite meeting of the AFREhealth-CUGH Working Group (ACWG) at the CUGH 2021 virtual conference in March 2021 that provided insights on North-South and South-South global health partnerships, against the backdrop of the COVID-19 pandemic. The authors describe challenges and opportunities for research and education in these partnerships (as discussed at this ACWG Satellite meeting), and implications for the field of global health going forward as we emerge from the pandemic.

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities.

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.

Randomized controlled trials of interventions to prevent sexually transmitted infections: learning from the past to plan for the future.

Globally, sexually transmitted infections (STIs) represent a significant source of morbidity and disproportionately impact the health of women and children. The number of randomized controlled trials testing interventions to prevent STIs has dramatically increased over time. To assess their impact, the authors conducted a systematic review of interventions to prevent sexual transmission or acquisition of STIs other than human immunodeficiency virus, published in the English-language, peer-reviewed literature through December 2009. Ninety-three papers reporting data from 74 randomized controlled trials evaluating 75 STI prevention interventions were identified. Eight intervention modalities were used: behavioral interventions (36% of interventions), vaginal microbicides (16%), vaccines (16%), treatment (11%), partner services (9%), physical barriers (5%), male circumcision (5%), and multicomponent (1%). Overall, 59% of interventions demonstrated efficacy in preventing infection with at least 1 STI. Treatment interventions and vaccines for viral STIs showed the most consistently positive effects. Male circumcision protected against viral STIs and possibly trichomoniasis. Almost two-thirds of behavioral interventions were effective, but the magnitude of effects ranged broadly. Partner services yielded similarly mixed results. In contrast, vaginal microbicides and physical barrier methods demonstrated few positive effects. Future STI prevention efforts should focus on enhancing adherence within interventions, integrating new technologies, ensuring sustainable behavior change, and conducting implementation research.

Evaluating and optimizing the consolidated framework for implementation research (CFIR) for use in low- and middle-income countries: a systematic review.

BACKGROUND: The Consolidated Framework for Implementation Research (CFIR) is a determinants framework that may require adaptation or contextualization to fit the needs of implementation scientists in low- and middle-income countries (LMICs). The purpose of this review is to characterize how the CFIR has been applied in LMIC contexts, to evaluate the utility of specific constructs to global implementation science research, and to identify opportunities to refine the CFIR to optimize utility in LMIC settings. METHODS: A systematic literature review was performed to evaluate the use of the CFIR in LMICs. Citation searches were conducted in Medline, CINAHL, PsycINFO, CINAHL, SCOPUS, and Web of Science. Data abstraction included study location, study design, phase of implementation, manner of implementation (ex., data analysis), domains and constructs used, and justifications for use, among other variables. A standardized questionnaire was sent to the corresponding authors of included studies to determine which CFIR domains and constructs authors found to be compatible with use in LMICs and to solicit feedback regarding ways in which CFIR performance could be improved for use in LMICs. RESULTS: Our database search yielded 504 articles, of which 34 met final inclusion criteria. The studies took place across 21 countries and focused on 18 different health topics. The studies primarily used qualitative study designs (68%). Over half (59%) of the studies applied the CFIR at study endline, primarily to guide data analysis or to contextualize study findings. Nineteen (59%) of the contacted authors participated in the survey. Authors unanimously identified culture and engaging as compatible with use in global implementation research. Only two constructs, patient needs and resources and individual stages of change were commonly identified as incompatible with use. Author feedback centered on team level influences on implementation, as well as systems characteristics, such as health system architecture. We propose a "Characteristics of Systems" domain and eleven novel constructs be added to the CFIR to increase its compatibility for use in LMICs. CONCLUSIONS: These additions provide global implementation science practitioners opportunities to account for systems-level determinants operating independently of the implementing organization. Newly proposed constructs require further reliability and validity assessments. TRIAL REGISTRATION: PROSPERO, CRD42018095762.

Informing Rift Valley Fever preparedness by mapping seasonally varying environmental suitability.

BACKGROUND: Rift Valley Fever (RVF) poses a threat to human and animal health throughout much of Africa and the Middle East and has been recognized as a global health security priority and a key preparedness target. METHODS: We combined RVF occurrence data from a systematic literature review with animal notification data from an online database. Using boosted regression trees, we made monthly environmental suitability predictions from January 1995 to December 2016 at a 5 × 5-km resolution throughout regions of Africa, Europe, and the Middle East. We calculated the average number of months per year suitable for transmission, the mean suitability for each calendar month, and the "spillover potential," a measure incorporating suitability with human and livestock populations. RESULTS: Several countries where cases have not yet been reported are suitable for RVF. Areas across the region of interest are suitable for transmission at different times of the year, and some areas are suitable for multiple seasons each year. Spillover potential results show areas within countries where high populations of humans and livestock are at risk for much of the year. CONCLUSIONS: The widespread environmental suitability of RVF highlights the need for increased preparedness, even in countries that have not previously experienced cases. These maps can aid in prioritizing long-term RVF preparedness activities and determining optimal times for recurring preparedness activities. Given an outbreak, our results can highlight areas often at risk for subsequent transmission that month, enabling decision-makers to target responses effectively.

The arc of HIV epidemics in sub-Saharan Africa: new challenges with concentrating epidemics in the era of 90-90-90.

PURPOSE OF REVIEW: The aim of this review is to examine the emerging results from the HIV universal test and treat (UTT) cluster-randomized trials in sub-Saharan Africa, discuss how expanding access to HIV clinical services is likely to reshape the arc of HIV epidemics, and consider implications for HIV prevention and control strategies in the coming decade. RECENT FINDINGS: The effect of universal HIV testing followed by immediate antiretroviral treatment (ART) on community-level HIV incidence remains unclear upon completion of five randomized trials. Only two of the four trials that measured HIV incidence found significant reductions in community-level incidence. Even in these trials, HIV incidence remained above levels required for epidemic control (≤1 case per 1000 person-years) despite high levels of ART coverage and viral suppression. These findings may indicate that community-delivered HIV services are not reaching the high-frequency transmitters who sustain HIV epidemics and are likely members of marginalized or hard to engage core groups. SUMMARY: With expanded access to HIV services in sub-Saharan Africa, HIV epidemics are transitioning from hyperendemic to declining/endemic epidemic phases, characterized increasingly by the reconcentration of HIV in marginalized or hard to engage core groups. To move toward epidemic control, novel HIV service delivery models and technologies are needed to engage those who continue to drive HIV incidence in this new epidemic phase.

Persisting with prevention: the importance of adherence for HIV prevention.

BACKGROUND: Only four out of 31 completed randomized controlled trials (RCTs) of HIV prevention strategies against sexual transmission have shown significant efficacy. Poor adherence may have contributed to the lack of effect in some of these trials. In this paper we explore the impact of various levels of adherence on measured efficacy within an RCT. ANALYSIS: We used simple quantitative methods to illustrate the impact of various levels of adherence on measured efficacy by assuming a uniform population in terms of sexual behavior and the binomial model for the transmission probability per partnership.At 100% adherence the measured efficacy within an RCT is a reasonable approximation of the true biological efficacy. However, as adherence levels fall, the efficacy measured within a trial substantially under-estimates the true biological efficacy. For example, at 60% adherence, the measured efficacy can be less than half of the true biological efficacy. CONCLUSION: Poor adherence during a trial can substantially reduce the power to detect an effect, and improved methods of achieving and maintaining high adherence within trials are needed. There are currently 12 ongoing HIV prevention trials, all but one of which require ongoing user-adherence. Attention must be given to methods of maximizing adherence when piloting and designing RCTs and HIV prevention programmes.

Implementation science for integration of HIV and non-communicable disease services in sub-Saharan Africa: a systematic review.

OBJECTIVE: As the burden of chronic non-communicable diseases (NCDs) rises across sub-Saharan Africa (SSA), global donors and governments are exploring strategies to integrate HIV and NCD care. Implementation science is an emerging research paradigm that can help such programs achieve health impact at scale. We define implementation science as a systematic, scientific approach to ask and answer questions about how to deliver what works in populations who need it with greater speed, appropriate fidelity, efficiency, and relevant coverage. We identified achievements and gaps in the application of implementation science to HIV/NCD integration, developed an HIV/NCD implementation science research agenda, and detailed opportunities for capacity building and training. DESIGN: We conducted a systematic review of the application of implementation science methods to integrated HIV/NCD programs in SSA. METHODS: We searched PubMed, CINAHL, PsycINFO, and EMBASE for evaluations of integrated programs in SSA reporting at least one implementation outcome. RESULTS: We identified 31 eligible studies. We found that most studies used only qualitative, economic, or impact evaluation methods. Only one study used a theoretical framework for implementation science. Acceptability, feasibility, and penetration were the most frequently reported implementation outcomes. Adoption, appropriateness, cost, and fidelity were rare; sustainability was not evaluated. CONCLUSIONS: Implementation science has a promising role in supporting HIV/NCD integration, although its impact will be limited unless theoretical frameworks, rigorous study designs, and reliable measures are employed. To help support use of implementation science, we need to build sustainable implementation science capacity. Doing so in SSA and supporting implementation science investigators can help expedite HIV/NCD integration.