Mortality Among HIV-Infected Adults on Antiretroviral Therapy in Southern Uganda.

BACKGROUND: Monitoring and evaluation of clinical programs requires assessing patient outcomes. Numerous challenges complicate these efforts, the most insidious of which is loss to follow-up (LTFU). LTFU is a composite outcome, including individuals out of care, undocumented transfers, and unreported deaths. Incorporation of vital status information from routine patient outreach may improve the mortality estimates for those LTFU. SETTINGS: We analyzed routinely collected clinical and patient tracing data for individuals (15 years or older) initiating antiretroviral treatment between January 2014 and December 2018 at 2 public HIV care clinics in greater Rakai, Uganda. METHODS: We derived unadjusted mortality estimates using Kaplan-Meier methods. Estimates, adjusted for unreported deaths, applied weighting through the Frangakis and Rubin method to represent outcomes among LTFU patients who were successfully traced and for whom vital status was ascertained. Confidence intervals were determined through bootstrap methods. RESULTS: Of 1969 patients with median age at antiretroviral treatment initiation of 31 years (interquartile range: 25-38), 1126 (57.2%) were female patients and 808 (41%) were lost. Of the lost patients, 640 patient files (79.2%) were found and reviewed, of which 204 (31.8%) had a tracing attempt. Within the electronic health records of the program, 28 deaths were identified with an estimated unadjusted mortality 1 year after antiretroviral treatment initiation of 2.5% (95% CI: 1.8% to 3.3%). Using chart review and patient tracing data, an additional 24 deaths (total 52) were discovered with an adjusted 1-year mortality of 3.8% (95% CI: 2.6% to 5.0%). CONCLUSIONS: Data from routine outreach efforts by HIV care and treatment programs can be used to support plausible adjustments to estimates of client mortality. Mortality estimates without active ascertainment of vital status of LTFU patients may significantly underestimate program mortality.

Practices and attitudes of herbalists regarding informed consent in Uganda: A qualitative study.

Background: Informed consent (IC) is a fundamental principle in medical ethics that upholds respect for patient autonomy. Although widely applied in healthcare, its feasibility and implementation in herbal medicine have been underexplored. This study therefore aimed to explore the practices and attitudes of herbalists regarding informed consent. Methods: To achieve these objectives, a qualitative cross-sectional study was conducted from June to December 2020. Twenty-one in-depth interviews with herbalists and four key informant interviews with leaders of the different traditional medicine organizations were also conducted. The data were analyzed thematically using NVivo version 12 software. Results: Sixteen of the twenty-one participants acquired oral herbal medicine knowledge from their relatives. Although a positive inclination toward obtaining IC was evident, the focus was on disclosing basic information. Discussions of alternative treatments and herbal specifics less frequent. Disease management decisions often involve shared responsibility within families or societies. Documented IC procedures are rare among herbalists, who deem consent forms unnecessary, although they recognize the potential benefits of IC in fostering trust and professionalism. Challenges hindering IC implementation included regulatory gaps, inadequate skills, and the absence of mechanisms to protect the intellectual property rights of herbal medicine. Conclusion: This study illuminates how educational, cultural, familial, and regulatory factors influence herbalists' practices and attitudes toward informed consent.

Exploration of Clinical Ethics Consultation in Uganda: A case study of Uganda Cancer Institute.

Introduction: Globally, healthcare providers (HCPs), hospital administrators, patients and their caretakers are increasingly confronted with complex moral, social, cultural, ethical, and legal dilemmas during clinical care. In high-income countries (HICs), formal and informal clinical ethics support services (CESS) have been used to resolve bioethical conflicts among HCPs, patients, and their families. There is limited evidence of mechanisms used to resolve these issues as well as experiences and perspectives of the stakeholders that utilize them in most African countries including Uganda. Methodology: This qualitative study utilized in-depth-interviews (IDIs) and focus group discussions (FGDs) to collect data from Uganda Cancer Institute (UCI) staff, patients, and caretakers, who were purposively selected. Data was analyzed deductively and inductively yielding themes and sub-themes that were used to develop a codebook. Results: There was no formal committee nor mechanism utilized to resolve ethical dilemmas at the UCI. The study uncovered six fora where ethical dilemmas were addressed: individual consultations, tumor board meetings, morbidity and mortality meetings, core management meetings, rewards and sanctions committee meetings, and clinical departmental meetings. Participants expressed apprehension regarding the efficacy of these fora due to their non-ethics related agendas as well as members lacking training in medical ethics and the necessary experience to effectively resolve ethical dilemmas. Conclusion: The fora employed at the UCI to address ethical dilemmas were implicit, involving decisions made through various structures without the guidance of personnel well-versed in medical or clinical ethics. There was a strong recommendation from participants to establish a multidisciplinary clinical ethics committee comprising members who are trained, skilled, and experienced in medical and clinical ethics.

Exploring the diverse definitions of 'evidence': a scoping review.

OBJECTIVES: To systematically collect and analyse diverse definitions of 'evidence' in both health and social sciences, and help users to correctly use the term 'evidence' and rethink what is the definition of 'evidence' in scientific research. DESIGN: Scoping review. METHODS: Definitions of evidence in the health sciences and social sciences were included. We have excluded the definition of evidence applied in the legal field, abstracts without full text, documents not published in either Chinese or English and so on. We established a multidisciplinary working group and systematically searched five electronic databases including Medline, Web of Science, EBSCO, the Chinese Social Sciences Citation Index and the Chinese Science Citation Database from their inception to 26 February 2022. We also searched websites and reviewed the reference lists of the identified studies. Six reviewers working in pairs, independently, selected studies according to the inclusion and exclusion criteria, and extracted information. Any differences were discussed in pairs, and if there was disagreement, it was resolved via discussion or with the help of a third reviewer. Reviewers extracted document characteristics, the original content for the definitions of 'evidence', assessed definitions as either intensional or extensional, and any citations for the given definition. RESULTS: Forty-nine documents were finally included after screening, and 68 definitions were obtained. After excluding duplicates, a total of 54 different definitions of 'evidence' were identified. There were 42 intensional definitions and 12 extensional definitions. The top three definiens were 'information', 'fact' and 'research/study'. The definition of 'evidence' differed between health and social sciences. The term 'research' appeared most frequently in the definitions. CONCLUSIONS: The definition of 'evidence' has gradually attracted the attention of many scholars and decision-makers in health and social sciences. Nevertheless, there is no widely recognised and accepted definition in scientific research. Given the wide use of the term, we need to think about whether, or under what circumstances, a standardised, clear, meaningful and widely applicable definition of 'evidence' might be helpful.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Feasibility and outcomes of using DIALOG+ in primary care to improve quality of life and mental distress of patients with long-term physical conditions: an exploratory non-controlled study in Bosnia and Herzegovina, Colombia and Uganda.

INTRODUCTION: The management of long-term physical conditions is a challenge worldwide, absorbing a majority resources despite the importance of acute care. The management of these conditions is done largely in primary care and so interventions to improve primary care could have an enormous impact. However, very little data exist on how to do this. Mental distress is frequently comorbid with long term physical conditions, and can impact on health behaviour and adherence, leading to poorer outcomes. DIALOG+ is a low-cost, patient-centred and solution-focused intervention, which is used in routine patient-clinician meetings and has been shown to improve outcomes in mental health care. The question arises as to whether it could also be used in primary care to improve the quality of life and mental health of patients with long-term physical conditions. This is particularly important for low- and middle-income countries with limited health care resources. METHODS: An exploratory non-controlled multi-site trial was conducted in Bosnia and Herzegovina, Colombia, and Uganda. Feasibility was determined by recruitment, retention, and session completion. Patient outcomes (quality of life, anxiety and depression symptoms, objective social situation) were assessed at baseline and after three approximately monthly DIALOG+ sessions. RESULTS: A total of 117 patients were enrolled in the study, 25 in Bosnia and Herzegovina, 32 in Colombia, and 60 in Uganda. In each country, more than 75% of anticipated participants were recruited, with retention rates over 90% and completion of the intervention exceeding 92%. Patients had significantly higher quality of life and fewer anxiety and depression symptoms at post-intervention follow-up, with moderate to large effect sizes. There were no significant improvements in objective social situation. CONCLUSION: The findings from this exploratory trial suggest that DIALOG+ is feasible in primary care settings for patients with long-term physical conditions and may substantially improve patient outcomes. Future research may test implementation and effectiveness of DIALOG+ in randomized controlled trials in wider primary care settings in low- and middle-income countries. TRIAL REGISTRATION: All studies were registered prospectively within the ISRCTN Registry. ISRCTN17003451, 02/12/2020 (Bosnia and Herzegovina), ISRCTN14018729, 01/12/2020 (Colombia) and ISRCTN50335796, 02/12/2020 (Uganda).

Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial.

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases.

Use of the informed health choices educational intervention to improve secondary students' ability to think critically about health interventions in Uganda: A cluster-randomized trial.

AIM: The aim was to evaluate the effect of the Informed Health Choices (IHC) educational intervention on secondary students' ability to assess health-related claims and make informed choices. METHODS: In a cluster-randomized trial, we randomized 80 secondary schools (students aged 13-17 years) in Uganda to the intervention or control (usual curriculum). The intervention included a 2-day teacher training workshop, 10 lessons accessed online by teachers and delivered in one school term. The lesson plans were developed for classrooms equipped with a blackboard or a blackboard and projector. The lessons addressed nine prioritized concepts. We used two multiple-choice questions for each concept to evaluate the students' ability to assess claims and make informed choices. The primary outcome was the proportion of students with a passing score (≥9 of 18 questions answered correctly). RESULTS: Eighty schools consented and were randomly allocated. A total of 2477 students in the 40 intervention schools and 2376 students in the 40 control schools participated in this trial. In the intervention schools, 1364 (55%) of students that completed the test had a passing score compared with 586 (25%) of students in the control schools (adjusted difference 33%, 95% CI 26%-39%). CONCLUSIONS: The IHC secondary school intervention improved students' ability to think critically and make informed choices. Well-designed digital resources may improve access to educational material, even in schools without computers or other information and communication technology (ICT). This could facilitate scaling-up use of the resources and help to address inequities associated with limited ICT access.

Effects of the Informed Health Choices secondary school intervention: A prospective meta-analysis.

AIM: The aim of this prospective meta-analysis was to synthesize the results of three cluster-randomized trials of an intervention designed to teach lower-secondary school students (age 14-16) to think critically about health choices. METHODS: We conducted the trials in Kenya, Rwanda, and Uganda. The intervention included a 2- to 3-day teacher training workshop, digital resources, and ten 40-min lessons. The lessons focused on nine key concepts. We did not intervene in control schools. The primary outcome was a passing score on a test (≥9 of 18 multiple-choice questions answered correctly). We performed random effects meta-analyses to estimate the overall adjusted odds ratios. Secondary outcomes included effects of the intervention on teachers. RESULTS: Altogether, 244 schools (11,344 students) took part in the three trials. The overall adjusted odds ratio was 5.5 (95% CI: 3.0-10.2; p < 0.0001) in favor of the intervention (high certainty evidence). This corresponds to 33% (95% CI: 25-40%) more students in the intervention schools passing the test. Overall, 3397 (58%) of 5846 students in intervention schools had a passing score. The overall adjusted odds ratio for teachers was 13.7(95% CI: 4.6-40.4; p < 0.0001), corresponding to 32% (95% CI: 6%-57%) more teachers in the intervention schools passing the test (moderate certainty evidence). Overall, 118 (97%) of 122 teachers in intervention schools had a passing score. CONCLUSIONS: The intervention led to a large improvement in the ability of students and teachers to think critically about health choices, but 42% of students in the intervention schools did not achieve a passing score.

Effects of the Informed Health Choices secondary school intervention on the ability of students in Rwanda to think critically about health choices: A cluster-randomized trial.

AIM: The aim of this trial was to evaluate the effects of the Informed Health Choices intervention on the ability of students in Rwandan to think critically and make Informed Health Choices. METHODS: We conducted a two-arm cluster-randomized trial in 84 lower secondary schools from 10 districts representing five provinces of Rwanda. We used stratified randomization to allocate schools to the intervention or control. One class in each intervention school had ten 40-min lessons taught by a trained teacher in addition to the usual curriculum. Control schools followed the usual curriculum. The primary outcome was a passing score (≥ 9 out of 18 questions answered correctly) for students on the Critical Thinking about Health Test completed within 2 weeks after the intervention. We conducted an intention-to-treat analysis using generalized linear mixed models, accounting for the cluster design using random intercepts. RESULTS: Between February 25 and March 29, 2022, we recruited 3,212 participants. We assigned 1,572 students and 42 teachers to the intervention arm and 1,556 students and 42 teachers to the control arm. The proportion of students who passed the test in the intervention arm was 915/1,572 (58.2%) compared to 302/1,556 (19.4%) in the control arm, adjusted odds ratio 10.6 (95% CI: 6.3-17.8), p < 0.0001, adjusted difference 37.2% (95% CI: 29.5%-45.0%). CONCLUSIONS: The intervention is effective in helping students think critically about health choices. It was possible to improve students' ability to think critically about health in the context of a competence-based curriculum in Rwanda, despite challenging postpandemic conditions.

Effects of the informed health choices secondary school intervention on the ability of students in Kenya to think critically about health choices: A cluster-randomized trial.

AIM: There is an overabundance of claims about the advantages and disadvantages of health interventions. People need to be able to appraise the reliability of these claims. The aim of this two-arm cluster-randomized trial was to evaluate the Informed Health Choices secondary school intervention designed to teach students to assess claims about the effects of health actions and make informed decisions. METHODS: We conducted the trial among students from 80 secondary schools in five subcounties in Kenya. We used stratified randomization to allocate schools to the intervention or control arm. The intervention included a 2-day teacher training workshop and 10 lessons that addressed nine prioritized key concepts for assessing claims about treatment effects. We did not intervene in the control schools. The primary outcome was the proportion of students with a passing score (≥ 9/18 correct answers) on the Critical Thinking about Health test, which included two multiple-choice questions for each concept. RESULTS: Between May 11, 2022, and July 8, 2022, we recruited 3362 students and 80 teachers. We allocated 1863 students and 40 teachers to the intervention and 1499 students and 40 teachers to the control arm. In the intervention schools, 1149/1863 (61.7%) of students achieved a passing score compared to 511/1499 (34.1%) in the control schools (odds ratio 3.6 (95% CI 2.5-5.2), p < 0.0001). CONCLUSIONS: The intervention had a large effect on students' ability to think critically about health interventions. It is possible to integrate the learning of critical thinking about health within Kenya secondary school curriculum.

Cango Lyec (Healing the Elephant): HIV Prevalence and Vulnerabilities Among Adolescent Girls and Young Women in Postconflict Northern Uganda.

OBJECTIVES: Adolescent girls and young women younger than 25 years (AGYW) account for disproportionate HIV infections in sub-Saharan Africa. Impacts of war in Northern Uganda continue to affect HIV-related health and wellbeing of young people postconflict. Prevalence and incidence of HIV infection were estimated, and factors associated with HIV prevalence among sexually active AGYW in Northern Uganda were investigated. METHODS: Cango Lyec is a cohort involving conflict-affected populations in Northern Uganda. Nine randomly selected communities in Gulu, Nwoya, and Amuru districts were mapped. House-to-house census was conducted. Consenting participants aged 13-49 years were enrolled over 3 study rounds (2011-2015), of whom 533 were AGYW and had ever had sex. Data were collected on trauma, depression, and sociodemographic-behavioral characteristics. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression determined baseline factors associated with HIV prevalence. RESULTS: HIV prevalence among AGYW was 9.7% (95% CI: 7.3 to 12.6). AGYW living in Gulu (adjusted risk ratio, aRR: 2.48; 95% CI: 1.12 to 5.51) or Nwoya (aRR: 2.65; 95% CI: 1.03 to 6.83) were more likely than in Amuru to be living with HIV. Having self-reported genital ulcers (aRR: 1.93; 95% CI: 0.97 to 3.85) or active syphilis (aRR: 3.79; 95% CI: 2.35 to 6.12) was associated with increased risk of HIV infection. The likelihood of HIV was higher for those who experienced sexual violence in the context of war (aRR: 2.37; 95% CI: 1.21 to 4.62) and/or probable depression (aRR: 1.95; 95% CI: 1.08 to 3.54). HIV incidence was 8.9 per 1000 person-years. CONCLUSION: Ongoing legacies of war, especially gender violence and trauma, contribute to HIV vulnerability among sexually active AGYW. Wholistic approaches integrating HIV prevention with culturally safe initiatives promoting sexual and mental health in Northern Uganda are essential.

In the era of universal test and treat in Uganda, recent intimate partner violence is not associated with subsequent ART use or viral suppression.

Intimate partner violence (IPV) has been associated with delays throughout the HIV care continuum. This study explored prospective associations between experiences of past-year IPV and two HIV care outcomes in the context of current universal test and treat guidelines using two consecutive rounds of an ongoing HIV surveillance study conducted in the Rakai region of Uganda. Longitudinal logistic regression models examined associations between IPV, use of antiretroviral therapy (ART) and viral load suppression (VS), adjusting for outcome variables at baseline. To address differences in ART retention by IPV, propensity scores were used to create inverse-probability-of-treatment-and-censoring-weighted (IPTCW) models. At baseline, of 1923 women with HIV (WWH), 34.6%, 26.5%, 13.5% reported past-year verbal, physical and sexual IPV; a lower proportion of persons who experienced physical IPV (79.4%) were VS than those who did not (84.3%; p = 0.01). The proportion VS at baseline also significantly differed by exposure to verbal IPV (p = 0.03). However, in adjusted longitudinal models, IPV was not associated with lower odds of ART use or VS at follow-up. Among WWH in the Rakai region, IPV does not appear to be a barrier to subsequent ART use or VS. However, given the prevalence of IPV in this population, interventions are needed.

Exploring HIV/AIDS investigator perceptions of equity within research partnerships between low-and middle-income and high-income countries: a pilot survey.

BACKGROUND: Recommendations for research partnerships between low- and middle-income countries (LMICs) and high-income countries (HICs) stress the importance of equity within the collaboration. However, there is limited knowledge of the practical challenges and successes involved in establishing equitable research practices. This study describes the results of a pilot survey assessing key issues on LMIC/HIC partnership equity within HIV/AIDS research collaborations and compares perspectives of these issues between LMIC- and HIC-based investigators. METHODS: Survey participants were selected using clustered, random sampling and snowball sampling. Responses were compared between LMIC and HIC respondents using standard descriptive statistics. Qualitative respondent feedback was analyzed using a combination of exploratory and confirmatory thematic analysis. RESULTS: The majority of categories within four themes (research interests and resources; leadership, trust, and communication; cultural and ethical competence; representation and benefits) demonstrated relative consensus between LMIC and HIC respondents except for 'lack of trust within the partnership' which was rated as a more pronounced challenge by LMIC respondents. However, subcategories within some of the themes had significant differences between respondent groups including: equitable setting of the research agenda, compromise within a partnership, the role of regulatory bodies in monitoring partnerships for equity, and post-study access to research technology. CONCLUSIONS: These efforts serve as a proof-of-concept survey characterizing contemporary issues around international research partnership equity. The frequency and severity of specific equity issues can be assessed, highlighting similarities versus differences in experiences between LMIC and HIC partners as potential targets for further discussion and evaluation.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted, while HIV transmission to girls and women (aged 15-24 years) from older men declined by about one third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programs to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection.

Sub-Saharan Africa has increased morbidity and mortality related to chronic obstructive pulmonary disease (COPD). COPD among people living with HIV (PLWH) has not been well studied in this region, where HIV/AIDS is endemic. Increasing evidence suggests that respiratory microbial composition plays a role in COPD severity. Therefore, we aimed to investigate microbiome patterns and associations among PLWH with COPD in Sub-Saharan Africa. We conducted a cross-sectional study of 200 adults stratified by HIV and COPD in rural Uganda. Induced sputum samples were collected as an easy-to-obtain proxy for the lower respiratory tract microbiota. We performed 16S rRNA gene sequencing and used PICRUSt2 (version 2.2.3) to infer the functional profiles of the microbial community. We used a statistical tool to detect changes in specific taxa that searches and adjusts for confounding factors such as antiretroviral therapy (ART), age, sex, and other participant characteristics. We could cluster the microbial community into three community types whose distribution was shown to be significantly impacted by HIV. Some genera, e.g., Veillonella, Actinomyces, Atopobium, and Filifactor, were significantly enriched in HIV-infected individuals, while the COPD status was significantly associated with Gammaproteobacteria and Selenomonas abundance. Furthermore, reduced bacterial richness and significant enrichment in Campylobacter were associated with HIV-COPD comorbidity. Functional prediction using PICRUSt2 revealed a significant depletion in glutamate degradation capacity pathways in HIV-positive patients. A comparison of our findings with an HIV cohort from the United Kingdom revealed significant differences in the sputum microbiome composition, irrespective of viral suppression. IMPORTANCE Even with ART available, HIV-infected individuals are at high risk of suffering comorbidities, as shown by the high prevalence of noninfectious lung diseases in the HIV population. Recent studies have suggested a role for the respiratory microbiota in driving chronic lung inflammation. The respiratory microbiota was significantly altered among PLWH, with disease persisting up to 3 years post-ART initiation and HIV suppression. The community structure and diversity of the sputum microbiota in COPD are associated with disease severity and clinical outcomes, both in stable COPD and during exacerbations. Therefore, a better understanding of the sputum microbiome among PLWH could improve COPD prognostic and risk stratification strategies. In this study, we observed that in a virologically suppressed HIV cohort in rural Uganda, we could show differences in sputum microbiota stratified by HIV and COPD, reduced bacterial richness, and significant enrichment in Campylobacter associated with HIV-COPD comorbidity.

Makerere's contribution to the development of a high impact HIV research population-based cohort in the Rakai Region, Uganda.

Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV prevention, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.