Research | Rakai Health Sciences Program (2024)

The Rakai Community Cohort Study (RCCS) - Understanding its Significance

The Rakai Community Cohort Study (RCCS), initiated in 1994, stands as a pioneering effort in HIV research and population-based cohort studies. RCCS is an ongoing endeavour, enrolling consenting adult residents aged at least 15 years old from 30 continuously surveyed communities. Initially focused on individuals up to the age of 49, RCCS expanded its scope in 2021 to include older participants, broadening its reach and impact.

Data Collection and Methodology

RCCS collects a wealth of data through detailed interviews covering socio-demographic, behavioural, sexual network, mobility, and health-related aspects. Additionally, participants undergo non-communicable diseases risk assessments and provide blood samples for testing, facilitating comprehensive research endeavours.

Conducting Household Census

Prior to each survey visit, RCCS conducts household censuses, capturing vital information such as household composition, births, deaths, dwelling characteristics, and mobility data. This meticulous process ensures robust data collection and analysis.

Key Features and Contributions

RCCS serves as a cornerstone for various research initiatives, hosting over 40 nested studies and sub-studies over its 35-year history. Its extensive database and longitudinal design make it an invaluable resource for understanding HIV epidemiology, health service utilisation, and behavioural dynamics.

Health Services Evaluation and Clinical Trials

RCCS plays a pivotal role in evaluating health service delivery programs, including HIV care, voluntary medical male circumcision, and other health promotion initiatives. Moreover, it serves as a platform for conducting clinical trials, enabling researchers to develop and test hypotheses effectively.

RCCS Dashboard

The Rakai Community Cohort Study (RCCS)dashboard enables researchers to explore long-term HIV incidence and prevalence trends inagrarian, trading, and fishing communitieslocated in Rakai region of south-central, Uganda from 1994 to 2016. In addition, researchers can explore the impact of the combination HIV prevention strategy including HIV counseling and testing, voluntary medical male circumcision, antiretroviral therapy for participants living with HIV, and behavioral change on trends in HIV infection. Click here to visit the dashboard

Understanding the Sex Partner Study: Unravelling Genital Microbiome Dynamics

Introduction to the Study

The Sex Partner Study, also referred to as the 'Assessing dynamics of heterosexual transmission of genital bacteria and coital impact on microbiome composition/stability in the female and male genital tracts in South-central Uganda,' marks a groundbreaking initiative among African couples. It delves into the intricacies of penile-vagin*l sex's effects on genital microbiome composition and stability, examining the roles of various factors including biotic, abiotic, immune factors, and standard bacterial vaginosis (BV) treatment on the microbiota of both female and male genital tracts.

Primary Objectives

The primary objective of this study is to shed light on the sexual transmission of genital bacteria and elucidate the determinants influencing the penile microbiome post-sexual activity. By evaluating factors such as pH, oxygen levels, moisture, metabolites, and host and partner triad strains, researchers aim to gain insights that could lead to the development of novel antimicrobial treatments and enhance strategies like medical male circumcision to effectively mitigate HIV risk factors..

Methodology

Study activities involve the collection of pre- and post-coital samples to analyse the impact of penile-vagin*l sex and associated factors on the temporal composition and stability of the genital microbiome among heterosexual couples.

The Sex Partner Study represents a significant step forward in understanding the dynamics of genital microbiota and its implications for HIV transmission. By exploring the intricate interplay of various factors, this study holds promise for developing innovative approaches to reduce HIV risk factors and enhance overall sexual health outcomes.

Empowering Our Communities: Health Education and Community Mobilisation (HECM)

The Health Education and Community Mobilisation (HECM) section serves as the vital link between the Rakai Health Sciences Program (RHSP) and the communities where research and program activities are carried out. With a primary focus on community engagement, the HECM section plays a pivotal role in fostering awareness, participation, and collaboration within these communities.

Core Functions

• Community Awareness: The HECM section is dedicated to raising awareness about RHSP research initiatives, as well as the various services and programs offered. Through targeted educational campaigns and outreach efforts, community members are informed about the importance of research participation and encouraged to actively engage in RHSP activities.
• Compliance and Participation: By fostering a sense of ownership and involvement, the HECM section aims to increase community compliance and participation in RHSP endeavours. Through community mobilisation efforts, individuals are encouraged to take an active role in their own health and well-being.
• Friendly Environment Creation: Creating a welcoming and supportive environment is paramount to the success of RHSP activities. The HECM section works to cultivate positive relationships and trust within communities, ensuring that research and program activities are conducted in a manner that is respectful and responsive to community needs.

Additional Activities

• Dissemination of Research Findings: The HECM section ensures that research findings are effectively communicated to the communities involved, fostering transparency and accountability.
• Preparation for Services: Communities are prepared and informed about the various services offered by RHSP, facilitating access and utilisation.
• Community Advisory Board (CAB) Collaboration: Working closely with the Community Advisory Board (CAB), the HECM section facilitates dialogue and feedback between research communities and RHSP, ensuring that research activities are conducted in a manner that is ethical, respectful, and beneficial to all parties involved.
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The HECM section serves as a cornerstone of community engagement within RHSP-supported areas. By fostering awareness, participation, and collaboration, the section contributes to the success and impact of RHSP research and program activities, ultimately improving health outcomes and well-being within the community.

Unveiling the Enigma of Hard-to-Reach Individuals: The Hard-to-Reach Research Study 2021-2024

Defining Hard-to-Reach (HTR) Persons

In the realm of the Rakai Community Cohort Study (RCCS), Hard-to-Reach (HTR) individuals pose a unique challenge. These are individuals who have eluded detection by the regular RCCS outreach efforts on at least two separate occasions. The repeated absence of these individuals raises concerns about potential differences between them and the surveyed population, necessitating a closer examination of conclusions drawn from the sampled data.

Objectives of the Hard-to-Research Study

The Hard-to-Research Study, spanning the years 2021-2024, embarks on a journey to unlock the mysteries surrounding HTR individuals, with the following aims:

Methodology and Research Approach

The core of this study revolves around characterising the sources of incident HIV infections through a multi-faceted approach:

• Partner Tracing: Identifying sexual partners of RCCS participants recently diagnosed with HIV (termed 'incident cases') and matching them with HIV-negative controls.
• Enrolment of Partners: Enrolling identified partners in the RCCS, irrespective of their residence or community boundaries.
• Next-Generation Sequencing: Obtaining HIV sequencing data from seroconverters and HIV-positive partners to validate self-reported partner networks, ascertain probable infecting partners, and delineate potential transmission dynamics.

The Hard-to-Research Study represents a pioneering effort to shed light on the enigmatic realm of hard-to-reach individuals in HIV research. By employing innovative methodologies and cutting-edge techniques, this study aims to not only deepen our understanding of HIV transmission dynamics but also pave the way for more effective prevention strategies, ultimately inching closer to the goal of HIV elimination by 2030.

Epidemiologyand Impact of the HIV, NCD, and Urbanization Syndemic in Africa.

Objectives

Aim 1: Characterize HIV-related and-unrelated risk factors for cardiopulmonary non-communicable diseases (CP-NCDs)in a novel Rural-to-Urban (R2U) African cohort.

Aim 2: Characterize the impact of airpollution and moderating effects of HIV on cardiopulmonary clinical outcomesamong R2U migrants.

Aim 3: Assess HIV and CP-NCDshealth services utilization patterns among R2U migrants [and design anintegrated HIV/CP-NCD intervention.

Methodology

The study is nested in RCCS. Rural to urban migrants (Masaka city and Kampalametropolitan) are the indexes. Each index is matched on sex, age, HIV statusand community with one rural to rural migrant and two non-migrant participants.

Activities

1. Spirometry:done on all eligible participants usingNDD software.

2. Echocardiography:2,847 participants had echocardiogram done on them during round one of thestudy.

3. Air-qualitymonitoring

​ a) Personalexposure air quality monitoring: Sets of carbon monoxide monitors and ECM monitorsare worn and placed in the cooking area for 48hours to capture carbon monoxideconcentration and PM_2.5 data.

b) AmbientAir Quality monitoring: we use purple airdevices that were placed in various places (17 in RCCS communities, placed atHealth facilities, 4 in Masaka and 4 in Kampala metropolitan). One wascollocated with BAM at Makerere University weather station and 3 werecollocated with Airqo devices. Onepurple air device was collocated with the E-sampler to RHSP headquarters fordata validation.

4. Ambulatory Blood pressure Monitoring:24our ABPM is done on a selected group of participants in the VICINITY study.

5. Dailymovement mapping: used GPS logger to map out theroutes and locations where participants passed or spent their time in 24hours.

SBS Department Overview:

The Social and Behavioral Sciences department (SBS) at Rakai Health Sciences Program (RHSP) focuses on gathering and analyzing qualitative research data (non-numerical data) to understand human behavior, attitudes, beliefs, and motivations. Overall, it enriches the understanding of human behavior, informing strategic decisions, and advancing knowledge in the field of HIV through rigorous inquiry.

Aims of the department:

Relevance of the SBS department within RHSP.

• Design, execute, and analyze qualitative research data that address specific research questions or objectives.
• Collaborate with in country and outside research partners, quantitative researchers, interdisciplinary teams, and stakeholders to integrate qualitative insights into broader research initiatives and interdisciplinary projects.
• Offer expertise in qualitative research methods, including study design, data collection, analysis techniques, and interpretation of findings, to support the research needs of the organization, universities, and collaborators.
• Provide actionable insights and recommendations based on qualitative research findings to inform strategic decisions, program development, policy formulation, and organizational practices.
• Communicate research findings through reports, presentations, publications, and other dissemination channels to share knowledge with internal and external stakeholders, contribute to discussions, and promote evidence-based practices.

PAST AND CURRENT RESEARCH AREAS/PROJECTS (Selected)

a.Assessing dynamics of heterosexual transmission of genital bacteria and coital impact on microbiome composition/stability in the female and male genital tracts in South-central Uganda (Sex Partner study)

Objective:

(Primary): To elucidate the sexual transmission of genital bacteria and the determinants of the penile microbiome after sex.

(Secondary): To qualitatively assess study participant perspectives and overall experience with study procedures.

b.PANGEA

Qualitative research to understand sexual relationships where phylogenetic links are missing (The Missing Links)

Objective: To better understand the sexual relationships of female RCCS participants who are part of the identified incomplete phylogenetic networks that reflect likely HIV transmission.

c.WHO

Cognitive Testing of a Survey Instrument to Assess Sexual Practices, Behaviors, and Health Related Outcomes:

Objective: To Refine a Standard Instument in English and other Language Versions by testing it in a variety of Demographic Cross Sections of the General Populations, e.g older persons, persons in rural areas worldwide.

d.PANGEA

Fishing and Inland Communities – Understanding Transmission Linkages and Networks.

Objective: To gain a deeper understanding into underlying factors that drive preferential migration of people living with HIV to high prevalence Lake Victoria fishing communities, and the reasons for lower ART use among these migrating populations.

e.Baseline, Midterm and End of Project Evaluation Protocol for Masaka Regional mechanism (Program Evaluation - Mid-Term, 2021 and End Term, 2022)

Objective:

1. To collect data that will inform improvement of program implementation so that services are provided more effectively and efficiently in the region and best practices shared with other IPs in the country.
2. To also inform RHSP, CDC and other stakeholders about program challenges, performance gaps, progress towards achievement of set targets and program outcomes (effectiveness) in a timely manner so that implementation strategies can be maintained, scaled up or modified where necessary.

f.Impact of COVID-19 Lockdown on HIV and Reproductive, Maternal, Neonatal, and Child Health (RMNCH) Services in Masaka region, Uganda (2020)

Objective:

To assess the impact of the COVID-19 lockdown on utilization of RMNCH and HIV services, and assess experiences and coping mechanisms in order to make recommendations to mitigate the impact of this and similar health emergencies in the future.

g.Exploration of psychological distress and cross-cultural adaptation of amental health measure for people living with HIV in Rakai, Uganda (2021)

Objective:

To explore mental health and psychosocial

issues among people living with HIV in rural Rakai

h.Structural and Social Transitions among Adolescents and young adults in Rakai (SSTAR): (2019 – 2020)

Long-term impact of universal treatment and dolutegravir on populationHIV virologic and incidence outcomes in Africa

Background

HIV treatment in Africa has evolveddramatically in recent years with the rollout of Universal Test-and-Treat(UTT). However, despite universal test and treat rollout, HIV incidence hasdeclined only modestly, with no African country on track to meet UNAIDS 2030targets for epidemic control. Control efforts are challenged by substantialnumbers of “hard-to-engage” HIV-positive persons who remain viremic2 .Relatedly, there have been significant increases in HIV drug resistance (HIVDR)with expanded antiretroviral therapy (ART). The growing threat of HIIV drugresistance propelled the recent roll-out of Dolutegravir (DTG), an integraseinhibitor with a high barrier to resistance. While Universal test and treat andDolutegravir may result in lower rates of viremia and HIVDR, there isconsiderable uncertainty about the magnitude and durability of theirpopulation-level impact, especially in the context of the coronavirus disease19 (COVID-19) global pandemic, which was disrupting African HIV prevention andtreatment programs supported by the United States President’s Emergency Planfor AIDS Relief (PEFAR).

Toaddress these issues, we are conducting the Longitudinal Viral Load andEpidemiological Watch (LONGVIEW) Study, a population-level, prospectiveassessment of durable viral load (VL) suppression (i.e., sustained suppressionover the life course), HIVDR, and incidence before and after COVID-19 emergencein southcentral Uganda. This study is nested within the Rakai Community CohortStudy (RCCS), a prospective, population-based study of ~20,000 persons, aged15-49 years, in 40 communities with HIV prevalence ranging from ~9 to 40% and~20% transmitted HIVDR. We measure Viral loads and perform deep sequence viralphylogenetics on all HIV-seropositive participants over 7 surveys (n~3800 persurvey) conducted between 2013 and 2025, spanning roll-out of Universal testand treat in 2017, Dolutegravir in 2019, and emergence of COVID-19 in 2020.

Objectives

Aim 1 – Thisstudy will quantify population and individual trends in viremia and HIV drugresistance.

Aim 2 -assess the impact COVID-19 on HIV treatment seeking, utilization, and provisionof care

Aim 3 -measure population HIV incidence trends as well as transmission risk across theinfection and care continuum

Ouroverarching hypothesis is that despite UTT and DTG rollout, the COVID-19pandemic will disrupt HIV services resulting in significant declines in durablepopulation VL suppression, increases in HIV-DR, including emergence of DTGresistance, and rising HIV incidence.

The Longview study follows individuals whoare in the Rakai community cohort study who are HIV positive and virallyunsuppressed according to the Ugandan national guidelines. These individualsare categorized into those who are newly diagnosed (group 2), with previousdiagnosis however never been on ART (group 3) and then those who are currentlyor have ever been on ART but are virally unsuppressed. These participants arefollowed up and an interview is conducted to establish if these clients are incare plus the facility of HIV/AIDs care and treatment and if not yet in care,then reasons for this are cited. There after clinical data about the identifiedparticipants at their respective clinics is extracted using a questionnaireidentifying if they are active in care or defaulting, past & current ARTregimens, CD4, current Viral loads, differentiated service delivery models andtime spent on ART at the facility. We also provide counselling basing on theirviral load.

InternationalEpidemiology Databases to Evaluate AIDS (IeDEA) Consortium

IeDEAcollects observational data representingover 2.2 million people living with and at risk for HIV, contributed by clinical centers and researchgroups in 44 countries. IeDEA conductsboth regional and global research. The investigators use the IeDEA platform toshare their multidisciplinary expertise and answer high-priority researchquestions. These include evaluating the HIV treatment cascade, co-infectionslike tuberculosis and hepatitis, cancers, and non-communicable diseases,including mental health and substance use disorders.

TheIeDEA community is composed of investigators, study coordinators, and datateams representing multiple countries, languages, and backgrounds. Consortiummembers meet regularly through interest-based Working Groups to guide thecollaborative research projects. Rakai Health Sciences Program is one of theclinical sites and research groups that contribute data to IeDEA.

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Rakai Orphans in Communities (ROC)

The loss of oneor both parents can have devastating consequences for children, adolescents,extended families, communities, and nations. Recently, improvements in HIVtreatment and prevention have led to dramatic declines in orphanhood. Thisappears to be the result of combination HIV prevention (CHP), particularlyexpanded access to highly effective antiretroviral therapy (ART) and decliningHIV-related mortality among adults – adults who are often parents. The declinesin HIV-related orphanhood proffer substantial benefits to children and youth,families, and their communities. Little is known about how declines inorphanhood among youth may have impacted social and economic factors thatinfluence HIV risk as orphans move into the adolescent and young adult (AYA)years.

The Rakai Orphansin Communities (ROC) Study explores the impact, measurement, and policy issuesat the intersection of orphanhood, HIV risk among AYA, adolescent socialtransitions, and family and social context. Impacts include HIV risk and socialand economic consequences. Measurement of age at orphaning will be a criticalcomponent of this proposal. In several studies, earlier age at orphaningappears to be related to more adverse outcomes. Thus, key issues are estimatingthe impact of orphanhood on social and behavior risk for HIV and how thatimpact may change based on the age at orphaning. An under-explored componentwhich we are to examine is the economic benefits of CHP weighed against thecosts. Using the rich resources of the Rakai Community Cohort Study (RCCS), wewill explore the relationship.

Improving understandingof Capacity to consent to biomedical HIV prevention Researchamong adolescents in Rakai Uganda (ICARE)

ICARE uses mixed methods todescribe adolescent capacity to consent to biomedical trials, such as HIVpre-exposure prophylaxis (PrEP) product trials. We will examine age-relateddifferences and identify actionable factors related to capacity to consent tobiomedical research. Findings will be used to construct a digital toolkit forincluding adolescents in biomedical research for research ethics committees(RECs) and institutional review boards (IRBs).

In our prior study of adolescentcapacity to consent to observational research in Uganda (R01HD091003- 03S1), weused the MacArthur Competence Assessment Tool for Clinical Research(MacCAT-CR), a highly flexible tool that has accumulated the most adolescentdata, and described age-related capacity of adolescents to consent tolower-risk research.

We will recruit equal groups of early, middle, andlate adolescents and matched guardians from households that have participatedin the open, longitudinal population-based Rakai Community Cohort Study (RCCS)and from households naïve to the RCCS (Total 438). We will use the MacCAT-CR to assess cognitivecapacity to provide simulated consent to an adolescent PrEP trial, modeledafter HPTN 084 (Safety & Efficacy of Long-Acting Cabotegravir for thePrevention of HIV), and conduct additional qualitative interviews (n=25 dyadsper age group) to illuminate processes of guardian and youth decision-making.We will assess whether age, gender, educational status, and literacy, as wellas PrEP eligibility, prior use, awareness, knowledge, stigma, medicationbeliefs, and peer norms, are associated with cognitive capacity scores. This isa timely moment to examine PrEP, an active area of global research withpotential benefits for youth. Findings will contribute to addressing a majorbarrier to participation through an examination of a critical area inbiomedical research ethics – the capacity of adolescents of different ages,levels of education, literacy, and need for prevention to comprehend elementsof informed consent and, therefore, to self-consent.

Empowering Our Communities: Health Education and Community Mobilisation (HECM)

The Health Education and Community Mobilisation (HECM) section serves as the vital link between the Rakai Health Sciences Program (RHSP) and the communities where research and program activities are carried out. With a primary focus on community engagement, the HECM section plays a pivotal role in fostering awareness, participation, and collaboration within these communities.

Core Functions

• Community Awareness: The HECM section is dedicated to raising awareness about RHSP research initiatives, as well as the various services and programs offered. Through targeted educational campaigns and outreach efforts, community members are informed about the importance of research participation and encouraged to actively engage in RHSP activities.
• Compliance and Participation: By fostering a sense of ownership and involvement, the HECM section aims to increase community compliance and participation in RHSP endeavours. Through community mobilisation efforts, individuals are encouraged to take an active role in their own health and well-being.
• Friendly Environment Creation: Creating a welcoming and supportive environment is paramount to the success of RHSP activities. The HECM section works to cultivate positive relationships and trust within communities, ensuring that research and program activities are conducted in a manner that is respectful and responsive to community needs.

Additional Activities

• Dissemination of Research Findings: The HECM section ensures that research findings are effectively communicated to the communities involved, fostering transparency and accountability.
• Preparation for Services: Communities are prepared and informed about the various services offered by RHSP, facilitating access and utilisation.
• Community Advisory Board (CAB) Collaboration: Working closely with the Community Advisory Board (CAB), the HECM section facilitates dialogue and feedback between research communities and RHSP, ensuring that research activities are conducted in a manner that is ethical, respectful, and beneficial to all parties involved.

The HECM section serves as a cornerstone of community engagement within RHSP-supported areas. By fostering awareness, participation, and collaboration, the section contributes to the success and impact of RHSP research and program activities, ultimately improving health outcomes and well-being within the community.