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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.

RationaleConvalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited.ObjectiveIn this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda.MeasurementsPatients with a positive SARS-CoV-2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalised and randomised to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR-negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/critical condition (defined as oxygen saturation Main resultsA total of 136 patients were randomised, 69 to CCP+SOC and 67 to SOC only. The median age was 50 years (IQR: 38.5–62.0), 71.3% were male and the median duration of symptom was 7 days (IQR=4–8). Time to viral clearance was not different between the CCP+SOC and SOC arms (median of 6 days (IQR=4–11) vs 4 (IQR=4–6), p=0.196). There were no statistically significant differences in secondary outcomes in CCP+SOC versus SOC: time to symptom resolution (median=7 (IQR=5–7) vs 7 (IQR=5–10) days, p=0.450), disease progression (9 (22.0%) vs 7 (24.0%) patients, p=0.830) and mortality (10 (14.5%) vs 8 (11.9%) deaths, p=0.476).ConclusionIn this African trial, CCP therapy did not result in beneficial virological or clinical improvements. Further trials are needed to determine subgroups of patients who may benefit from CCP in Africa.Trial registration numberNCT04542941.

Introduction: The association between HIV status and hypertension is not well described within sub-Saharan Africa. We examined prevalence and risk factors for hypertension among HIV positive and negative individuals living in a rural district of Uganda. Methods: We conducted a cross-sectional analysis in two concurrent cohorts of 600 HIV negative and 721 HIV seropositive individuals aged ≥35 years. Results: Of the 721 HIV positive participants, 59.8% were women and the median age was 44.3 years, while for HIV negative individuals, 55% were women and the median age was 47.8 years. Over 90% of HIV positive individuals were on antiretroviral treatment. The prevalence of hypertension (≥140/≥90 mmHg) was 33.5% in HIV negative individuals and 23.9% in HIV positive individuals. Age (adjusted OR = 1.05, 95% CI 1.03 to 1.06) and BMI (adjusted OR = 1.08, 95% CI 1.05 to 1.12) were associated with higher odds of hypertension. Having HIV was associated with lower odds of hypertension (adjusted OR = 0.66, 95% CI 0.50 to 0.88), lower systolic blood pressure (–5.1 mmHg, 95% CI: –7.4 to –2.4) and lower diastolic blood pressure (–4.0 mmHg, 95% CI: –5.6 to –2.5). We did not observe differences in the odds of hypertension by CD4 count, viral load or ART among HIV positive individuals in this sample. Conclusions: Hypertension was prevalent in one third of HIV negative individuals and in one fourth of HIV positive patients. While access to health information among individuals attending HIV clinics may explain observed differences, more research is needed to understand plausible biological and social mechanisms that could explain lower blood pressure among people living with HIV in Uganda.

Background Non-communicable diseases (NCDs) are an increasing global concern, with morbidity and mortality largely occurring in low- and middle-income settings. We established the prospective Rural Uganda Non-Communicable Disease (RUNCD) cohort to longitudinally characterize the NCD prevalence, progression, and complications in rural Africa. Methods We conducted a population-based census for NCD research. We systematically enrolled adults in each household among three sub-counties of the larger Nakaseke Health district and collected baseline demographic, health status, and self-reported chronic disease information. We present our data on self-reported chronic disease, as stratified by age, sex, educational attainment, and sub-county. Results A total of 16,694 adults were surveyed with 10,563 (63%) respondents enrolled in the self-reported study. Average age was 37.8 years (SD = 16.5) and 45% (7481) were male. Among self-reported diseases, hypertension (HTN) was most prevalent (6.3%). 1.1% of participants reported a diagnosis of diabetes, 1.1% asthma, 0.7% COPD, and 0.4% kidney disease. 2.4% of the population described more than one NCD. Self-reported HTN was significantly higher in the peri-urban subcounty than in the other two rural sub-counties (p Conclusions The RUNCD will establish one of the largest NCD patient cohorts in rural Africa. First analysis highlights the feasibility of systematically enrolling large numbers of adults living in a rural Ugandan district. In addition, our study demonstrates low levels of self-reported NCDs compared to the nation-wide established levels, emphasizing the need to better educate, characterize, and care for the majority of rural communities.

Background: World over, there are antiretroviral therapy naïve individuals infected with HIV who maintain their CD4+T cell count above 500 cells/µl over 7-10 years and viral loads well controlled below undetectable levels (termed elite controllers, ECs) or at least 2,000 copies/mL (termed viremic controllers, VCs) for at least 12 months. Mechanisms responsible for HIV control in these individuals have not been fully elucidated. We hypothesized that CD4+T cells from elite and viremic controllers are naturally resistant to HIV-1 infection by blocking R5-tropic viral entry. We conducted a case-controlled study in which archived peripheral blood from 31 ECs/VCs and 15 progressors were investigated using in vitro HIV-1 infectivity assays. Results: Briefly, we purified CD4+T cells from peripheral blood using EasySep CD4+ positive selection kit followed by CD4+T cell activation using IL-2, anti-CD28 and anti-CD3. Three days post-activation, CD4+T cells were spinoculated and co-cultured with vesicular stomatitis virus G (VSV-G)-pseudotyped HIV, R5 (ADA-enveloped)- and X4 (NL4.3-enveloped v)-tropic HIV-1. Three days post infection, we quantified and compared the percentage infection of CD4+T cells in cases and controls. We demonstrate that a subgroup of Ugandan elite and viremic controllers possess CD4+T cells that are specifically resistant to R5-tropic virus, remaining fully susceptible to X4-tropic virus. Conclusion: Our study suggests that a subgroup of Ugandan elite and viremic controllers naturally control HIV-1 infection by blocking R5-tropic viral entry. Further research is needed to explore mechanisms of HIV control in the African population.

An update of the International Primary Care Respiratory Group (IPCRG) Research Needs Statement is currently being undertaken using an e-Delphi method. The aim of this analysis is to identify the main respiratory research themes from the perspective of primary care practitioners worldwide. Participants were recruited via the IPCRG network of 34 member countries. An initial open questionnaire elicited participants’ views on the most important respiratory conditions seen in their daily practice and invited suggestions of 5-10 relevant research questions within these conditions in the following domains: diagnosis, management, monitoring, self-management and prognosis. Using thematic qualitative analysis we identified the main cross-cutting research themes. 112 participants (69% physicians, 10% nurses, 21% other, 64% had special interest in respiratory) from 27 countries responded with 608 suggested research questions. Asthma was reported as the most clinically important condition (25.7%) followed by COPD (24.5%) and URTI (5.8%). Five themes emerged from the thematic analysis: uncertainties about diagnosis/management of respiratory conditions; need for contextually relevant and accessible guidance; need for methods to improve patient empowerment and self-management; role of the wider healthcare team; need for simple point-of-care tests. The eDelphi method is successful in identifying relevant research questions and the main themes pertinent to primary care worldwide. These research questions now need to be prioritised for investigation by the international community.

In Sub-Saharan Africa, COPD remains prevalent but its association with HIV is not well characterized especially in rural settings. We assessed for COPD prevalence, associated factors and lung function profile among HIV-infected individuals attending ART clinics in rural Nakaseke district of Uganda. We enrolled HIV-positive participants from four HIV treatment centers in rural Uganda. Participants underwent spirometry testing following standard guidelines. We defined COPD as a post-bronchodilator FEV(1)/ FVC ratio less than the fifth percentile of the NHANES III African-American reference. We assessed for factors associated with COPD and lung function profiles using multivariable logistic and linear regression analyses. We analyzed data from 722 HIV-positive participants (mean age 48.0 years, 59.7% women). Over 90% of participants were on ART for a median duration of 4 years (IQR 2–7 years), with a median viral load of 0 copies/mL (IQR 0–0 copies/mL), current and baseline CD4+T cell count of 478 cells/mm(3) (IQR 346–663 cells/mm(3)) and 335 cells/mm(3) (IQR 187–523 cells/mm(3)) respectively. The prevalence of COPD was 6.22%. COPD was associated with worse respiratory symptoms and health status. History of pulmonary tuberculosis was strongly associated with COPD (adjusted OR=4.92, 95% CI 1.71 to 14.15, p=0.003) and reduced lung function. Use of ART, CD(4)+T cell count and viral load were not associated with COPD or reduced lung function. In conclusion, we report a COPD prevalence of 6.22% in HIV-infected individuals in rural Uganda. Pulmonary tuberculosis remains the strongest predictor of COPD risk and reduced lung function in well-controlled HIV.

Background Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda.Methods PBMCs previously collected from HIV-1 Elite controllers and non-controllers were thawed, CD4+ T cells isolated and then cultured in presence of Anti-CD3 & Anti-CD28 for 48 hours in a CO2 incubator. RNA was extracted and RT qPCR was done using QuantiTect Probe RT-PCR Kit in a Rotor gene Q real-time PCR machine. mRNA was quantified using the delta CT relative quantification method. DNA was extracted using Qiagen Blood Genomic DNA Kit, PCR amplified and sequenced the exon 2 of TRIM5α and the promoter region of the CyclophillinA gene. Sequence data were analyzed using Mutation Surveyor to identify Single Nucleotide Polymorphisms (SNPs).Results From the sequence analysis, the rs10838525 G>A mutation in exon 2 of TRIM5α was found only among elite controllers (30%) while the rs3824949 was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. rs17860048 was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p=0.6095; Cyclophilin A p=0.6389).Conclusion Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers.

Background: Throughout the world, there are antiretroviral therapy–naive HIV+ individuals who maintain elevated peripheral CD4+ T-cell counts, historically referred to as long-term nonprogressors (LTNPs). With recent improvements in viral load (VL) detection methods to levels as low as 20 copies per milliliter, 2 subsets of LTNPs have been defined: elite controllers (ECs), with undetectable VLs for at least 6–12 months, and viremic controllers (VCs), with VLs between 200 and 2000 copies per milliliter. ECs and VCs have been extensively studied in the developed world to determine underlying mechanisms responsible for virologic control. In sub-Saharan Africa, most studies have characterized LTNPs based on immunologic criteria making it difficult to compare findings with the Western cohorts, which use virologic criteria. Here, we describe a cohort of Uganda ECs and VCs attending a large HIV ambulatory center in Kampala, Uganda, based initially on CD4 counts and confirmed by repeated VL measurements. Methods: A cross-sectional study was conducted among 14,492 HIV-infected, antiretroviral therapy–naive individuals aged 18 years and older under care for at least 5 years with serial peripheral CD4 counts ≥500 cells/μL. Among those, we determined the frequency of individuals with VLs

Background Pulmonary tuberculosis (TB) is the leading infectious cause of death globally with an estimated 1.7 billion people currently infected with Mycobacterium tuberculosis and at risk of developing TB. While the treatment of drug-susceptible pulmonary TB is highly effective, up to 50% of TB survivors have varying degrees of residual pathological and functional conditions potentially leading to chronic sequelae. Post-TB patients have reported respiratory symptoms, reduced quality of life, and increased risk of mortality. The objectives of this study are to describe the prevalence and lung function in individuals with post-TB exposure status in Uganda. Methods We performed a secondary data analysis of the Lung Function in Nakaseke and Kampala (LiNK) study, which is a population-based cohort in urban and rural settings in Uganda. Trained fieldworkers randomly selected homes and administered standard questionnaires to adults 35 years or older that were full-time residents of each setting. Prior TB diagnosis and treatment was self-reported by participants. Results Among the study population (N = 1559), 50 participants (3.2%) self-reported successfully treated TB. Among this subset of participants 21 (42.0%) were HIV positive, 9 (18.0%) were ever smokers, 6 (12.0%) were current smokers, and no participants had a prior COPD diagnosis. Mean (SD) age and body-mass index (BMI) at enrollment was 48.5 (SD 10.7) years and 22.2 (SD 3.9) kg/m2 respectively. The mean ± SD pre-bronchodilator FEV1/FVC was 72.9% (12.1%) for patients with successfully treated TB and 79.6% (0.08%) (p< 0.0001) for those without prior TB. Within these groups, 30% of patients with successfully treated TB and 9% of patients without prior TB had an FEV1/FVC suggestive of possible COPD. Comparison of FEV1/FVC Conclusion We found a high burden of residual effects of pulmonary TB on lung function and development of COPD, potentially increasing the global burden of COPD. Screening for chronic respiratory diseases following successful TB treatment is needed to improve lung function. Further research is needed to study lung function and quality of life in TB survivors in LMICs, where the burden of pulmonary TB is highest. Disclosures All Authors: No reported disclosures

Hypertension is diagnosed and treated based on blood pressure (BP) readings obtained in the clinic setting. Positive HIV status is associated with a higher prevalence of abnormal diurnal BP patterns, diagnosed with ambulatory BP monitoring rather than the conventional method of BP measurement. Little is known about ambulatory BP profiles in people living with HIV (PLHIV) in low-income countries, especially within sub-Saharan Africa. In this study, we compared 24-h ambulatory BP profiles of 140 HIV-positive individuals vs. profiles in 166 HIV negative individuals living in rural Uganda. HIV was well-controlled, with all HIV seropositive participants reporting use of anti-retroviral therapy, and ~123 (88%) having undetectable viral load. Most participants reported ART use duration of less than 10 years. Compared to HIV negative participants, HIV positive participants had lower median 24-h systolic BP (110.4 mmHg (IQR: 105.7, 118.7) vs 117.7 mmHg (IQR: 110.8, 129.8), p

As urbanization increases in low- and middle-income countries (LMICs), urban populations will be increasingly exposed to a range of environmental risk factors for non-communicable diseases. Inadequate living conditions in urban settings may influence mechanisms that regulate gene expression, leading to the development of non-communicable respiratory diseases. We conducted a systematic review of the literature to assess the relationship between respiratory health and epigenetic factors to urban environmental exposures observed in LMICs using MEDLINE, PubMed, EMBASE, and Google Scholar searching a combination of the terms: epigenetics, chronic respiratory diseases (CRDs), lung development, chronic obstructive airway disease, and asthma. A total of 2835 articles were obtained, and 48 articles were included in this review. We found that environmental factors during early development are related to epigenetic effects that may be associated with a higher risk of CRDs. Epigenetic dysregulation of gene expression of the histone deacetylase (HDAC) and histone acetyltransferase gene families was likely involved in lung health of slum dwellers. Respiratory-related environmental exposures influence HDAC function and deoxyribonucleic acid methylation and are important risk factors in the development of CRD. Additional epigenetic research is needed to improve our understanding of associations between environmental exposures and non-communicable respiratory diseases.

Background Unmet need for family planning exceeds 33% in Uganda. One approach to decreasing unmet need is promoting male involvement in family planning. Male disapproval of use of family planning by their female partners and misconceptions about side effects are barriers to family planning globally and in Uganda in particular. Researchers have conducted a number of qualitative studies in recent years to examine different aspects of family planning among Ugandan men. The present study aimed to quantify men’s knowledge of family planning in rural Uganda to understand how better to involve men in couples’ contraceptive decision-making, particularly in low-resource settings. Methods Data were derived from in-person, researcher-administered surveys of men in a rural agrarian district in Uganda (N = 178). Participant demographics and knowledge of family planning methods, side effects, and use were queried. Descriptive statistics were used for analysis. Results Men were 34 years of age on average (range 18–71) and about half (56%) had a primary school education or less. Ninety-eight percent reported any knowledge of family planning, with 73% of men reporting obtaining information via radio and only 43% from health workers. The most common method known by men was the male condom (72%), but more than half also knew of injections (54%) and pills (52%). Relatively few men reported knowing about the most effective reversible contraceptive methods, intrauterine devices and implants (both 16%). Men identified many common contraceptive side-effects, such as vaginal bleeding (31%), and misconceptions about side effects, such as increased risk of infertility and birth defects, were relatively uncommon (both

INTRODUCTION:Unintended pregnancy is a significant modifiable factor contributing to the high maternal mortality rate in Uganda. This study compares women and men’s knowledge of and attitudes toward family planning (FP) in rural Uganda to understand potential barriers to its use.METHODS:Data were co