Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status.

Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals.

Characteristics and phenotypes of a COPD cohort from referral hospital clinics in Uganda.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with varied clinical and pathophysiological characteristics. Although there is increasing evidence that COPD in low-income and middle-income countries may have different clinical characteristics from that in high-income countries, little is known about COPD phenotypes in these settings. We describe the clinical characteristics and risk factor profile of a COPD population in Uganda. METHODS: We cross sectionally analysed the baseline clinical characteristics of 323 patients with COPD aged 30 years and above who were attending 2 national referral outpatient facilities in Kampala, Uganda between July 2019 and March 2021. Logistic regression was used to determine factors associated with spirometric disease severity. RESULTS: The median age was 62 years; 51.1% females; 93.5% scored COPD Assessment Test >10; 63.8% modified medical research council (mMRC) >2; 71.8% had wheezing; 16.7% HIV positive; 20.4% had a history of pulmonary tuberculosis (TB); 50% with blood eosinophilic count >3%, 51.7% had 3 or more exacerbations in the past year. Greater severity by Global initiative for Chronic Obstructive Lung Disease (GOLD) stage was inversely related to age (aOR=0.95, 95% CI 0.92 to 0.97), and obesity compared with underweight (aOR=0.25, 95% CI 0.07 to 0.82). Regarding clinical factors, more severe airflow obstruction was associated with SPO2 <93% (aOR=3.79, 95% CI 2.05 to 7.00), mMRC ≥2 (aOR=2.21, 95% CI 1.08 to 4.53), and a history of severe exacerbations (aOR=2.64, 95% CI 1.32 to 5.26). CONCLUSION: Patients with COPD in this population had specific characteristics and risk factor profiles including HIV and TB meriting tailored preventative approaches. Further studies are needed to better understand the pathophysiological mechanisms at play and the therapeutic implications of these findings.

The Neutrophil-to-Lymphocyte Ratio as a Predictor of Acute Exacerbations Among Patients With COPD in Uganda.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive biomarker that potentially predicts acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). We evaluated the association of baseline NLR and respiratory hospitalization risk within one year among chronic obstructive pulmonary disease (COPD) patients in Uganda, a low- and middle-income country. Methods: A total of 312 COPD patients were followed for one year. Clinical characteristics and exacerbation rates were collected. Poisson regression with robust variance estimators was used to measure the association between NLR and hospital admissions due to COPD exacerbations. Receiver-operator characteristic (ROC) curves and the area under the curve were used to assess the ability of NLR to predict AECOPDs. Results: The median (Q 1, Q 3) age was 64 years (53, 71). Females comprised 50.96% (n=159) of the cohort, and 71.2% (n=222) of participants had moderate or severe COPD. A total of 9.9% (n=31) of participants experienced a COPD exacerbation during the period of follow-up. At baseline, the median (Q 1, Q 3) NLR ratio among participants who experienced an exacerbation was 1.46 (0.92, 2.33) compared to 1.03 (0.72,1.42) among those who did not experience one during the follow-up period (p=0.002). Using Youden and Liu's methods, the optimal NLR cutoff for predicting COPD exacerbation was 1.17. This cutoff resulted in a ROC curve area of 0.64 (95% confidence interval: 0.56, 0.73). Conclusion: The NLR could be used as a risk predictor, in low- and middle-income countries, for hospital admissions due to COPD exacerbations. A cutoff of 1.17 was an independent predictor of hospitalization due to acute exacerbations of COPD within one year.

Alcohol Consumption Modifies Susceptibility to HIV-1 Entry in Cervical Mucosa-Derived CD4+ T cells of Women Resident in a Fishing Community of Lake Victoria, Uganda.

Background: A significant overlap exists in the burden of Alcohol Use Disorders (AUDs) and the HIV epidemic in Sub-Saharan Africa. Over 60% of HIV infections occur in women, mostly through the cervical mucosa. Absorption and systemic circulation of alcohol induces global physiological and immune effects, including at the genital mucosa. Alcohol alters expression of cell surface receptors, mucosal barrier permeability, inflammatory responses, and lymphocyte trafficking and homing. However, a substantial knowledge gap exists on whether these cellular and or immunological effects of alcohol modify the consumers' CD4+ T cell susceptibility to HIV-1 entry at the cervical mucosa. HIV seronegative women, aged 18-49 years were recruited from Kasenyi and Kigungu fish landing sites of Lake Victoria. They were categorized as Alcohol Consumers (n=27) or non-Alcohol Consumers (n=26) based on the World Health Organization Alcohol-Use-Disorder-Test (WHO-AUDIT) at a cut-off score of >=8/40 and <8/40, respectively. Cytobrush-collected Cervical Mononuclear Cells [CMCs] and Peripheral Blood Mononuclear Cells [PBMCs] from heparinized whole-blood were surface stained for CD4+ T cell immunophenotyping. To measure susceptibility to HIV entry, CMCs and PBMCs were co-cultured overnight with equal amount of GFP-tagged HIV-1 pseudo-virus particles. Both immunophenotyping and HIV entry were measured on a BD LSR II flow cytometer. Results: There was no significant difference in the frequency of CD4+ T cells in blood (p=0.451) or mucosa (p=0.838) compartments across study groups. However, we observed a combined four-fold higher HIV entry (p=0.0001) into cervical versus blood-derived CD4+ T cells regardless of alcohol consumption status. More so, cervical-derived CD4+ T cells of alcohol-consumers showed a two-fold increase in susceptibility to HIV entry (P=0.0185) compared to the non-alcohol consumer group. Double positive α4ß7+CD4+T cells of alcohol consumers exhibited a higher HIV entry compared to those from alcohol non-consumers(p=0.0069). Conclusion: This study demonstrates that cervical CD4+ T cells are more susceptible to HIV entry than those from blood. Also, cervical CD4+ T cells of alcohol consumers are more susceptible than those of non-consumers. Differences in frequencies of α4ß7+ CD4+ T between alcohol consumers and non-consumers' cells may account for the increased susceptibility to HIV entry.

Mechanisms of lung damage in tuberculosis: implications for chronic obstructive pulmonary disease.

Pulmonary tuberculosis is increasingly recognized as a risk factor for COPD. Severe lung function impairment has been reported in post-TB patients. Despite increasing evidence to support the association between TB and COPD, only a few studies describe the immunological basis of COPD among TB patients following successful treatment completion. In this review, we draw on well-elaborated Mycobacterium tuberculosis-induced immune mechanisms in the lungs to highlight shared mechanisms for COPD pathogenesis in the setting of tuberculosis disease. We further examine how such mechanisms could be exploited to guide COPD therapeutics.

Reduced CCR5 expression among Uganda HIV controllers.

BACKGROUND: Several mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV control among HIV controllers. However, no one mechanism universally accounts for HIV control among all controllers. In this study we determined whether reduced CCR5 expression accounts for HIV control among Ugandan HIV controllers. We determined CCR5 expression among Ugandan HIV controllers compared with treated HIV non-controllers through ex-vivo characterization of CD4 + T cells isolated from archived PBMCs collected from the two distinct groups. RESULTS: The percentage of CCR5 + CD4 + T cells was similar between HIV controllers and treated HIV non-controllers (ECs vs. NCs, P = 0.6010; VCs vs. NCs, P = 0.0702) but T cells from controllers had significantly reduced CCR5 expression on their cell surface (ECs vs. NCs, P = 0.0210; VCs vs. NCs, P = 0.0312). Furthermore, we identified rs1799987 SNP among a subset of HIV controllers, a mutation previously reported to reduce CCR5 expression. In stark contrast, we identified the rs41469351 SNP to be common among HIV non-controllers. This SNP has previously been shown to be associated with increased perinatal HIV transmission, vaginal shedding of HIV-infected cells and increased risk of death. CONCLUSION: CCR5 has a non-redundant role in HIV control among Ugandan HIV controllers. HIV controllers maintain high CD4 + T cells despite being ART naïve partly because their CD4 + T cells have significantly reduced CCR5 densities.

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.

Prioritising primary care respiratory research needs: results from the 2020 International Primary Care Respiratory Group (IPCRG) global e-Delphi exercise.

Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.

24-hour ambulatory blood pressure monitoring and hypertension related risk among HIV-positive and HIV-negative individuals: cross sectional study findings from rural Uganda.

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 < 0.001), and 24-h diastolic BP (69.2 mmHg (IQR: 65.0, 74.9) vs. 71.9 mmHg (IQR: 67.2, 78.1), p = 0.004). Adjusted results showed greater percentage systolic nocturnal dipping among PLHIV compared to HIV negative individuals (difference = 2.70 (IQR: 0.94, 4.47), p < 0.05). Results of the adjusted Poisson regression suggested lower prevalence of 24-h and night hypertension among HIV positives compared to HIV negative, but were not statistically significant. Our data suggest that continuous 24-h BP measurements are lower in PLHIV on ART compared to HIV negative individuals.

Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) has significantly contributed to global mortality, with three million deaths reported annually. This impact is expected to increase over the next 40 years, with approximately 5 million people predicted to succumb to COPD-related deaths annually. Immune mechanisms driving disease progression have not been fully elucidated. Airway microbiota have been implicated. However, it is still unclear how changes in the airway microbiome drive persistent immune activation and consequent lung damage. Mechanisms mediating microbiome-immune crosstalk in the airways remain unclear. In this review, we examine how dysbiosis mediates airway inflammation in COPD. We give a detailed account of how airway commensal bacteria interact with the mucosal innate and adaptive immune system to regulate immune responses in healthy or diseased airways. Immune-phenotyping airway microbiota could advance COPD immunotherapeutics and identify key open questions that future research must address to further such translation.

The rural Uganda non-communicable disease (RUNCD) study: prevalence and risk factors of self-reported NCDs from a cross sectional survey.

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 < 0.001); diagnoses for all other diseases did not differ significantly between sub-counties. Odds for self-reported HTN increased significantly with age (OR = 1.87 per 10 years of age, 95% CI 1.78-1.96). Male sex was associated with lower odds of reporting asthma (OR = 0.53, 95% CI 0.34-0.82) or HTN (OR = 0.31, 95% CI 0.26-0.40). 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.

Efficacy of convalescent plasma for treatment of COVID-19 in Uganda.

RATIONALE: Convalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited. OBJECTIVE: In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda. MEASUREMENTS: Patients 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 <93% or needing oxygen), mortality and safety. MAIN RESULTS: A 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). CONCLUSION: In 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 number NCT04542941.

Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda.

INTRODUCTION: Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda. METHODS: In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors. RESULTS: 192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant. CONCLUSION: CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.

Association between Blood Pressure and HIV Status in Rural Uganda: Results of Cross-Sectional Analysis.

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.

Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda.

RATIONALE: Detailed data on the characteristics and outcomes of patients with COVID-19 in sub-Saharan Africa are limited. OBJECTIVE: We determined the clinical characteristics and treatment outcomes of patients diagnosed with COVID-19 in Uganda. MEASUREMENTS: As of the 16 May 2020, a total of 203 cases had been confirmed. We report on the first 56 patients; 29 received hydroxychloroquine (HCQ) and 27 did not. Endpoints included admission to intensive care, mechanical ventilation or death during hospitalisation. MAIN RESULTS: The median age was 34.2 years; 67.9% were male; and 14.6% were <18 years. Up 57.1% of the patients were asymptomatic. The most common symptoms were fever (21.4%), cough (19.6%), rhinorrhea (16.1%), headache (12.5%), muscle ache (7.1%) and fatigue (7.1%). Rates of comorbidities were 10.7% (pre-existing hypertension), 10.7% (diabetes) and 7.1% (HIV), Body Mass Index (BMI) of ≥30 36.6%. 37.0% had a blood pressure (BP) of >130/90 mm Hg, and 27.8% had BP of >140/90 mm Hg. Laboratory derangements were leucopenia (10.6%), lymphopenia (11.1%) and thrombocytopenia (26.3%). Abnormal chest X-ray was observed in 14.3%. No patients reached the primary endpoint. Time to clinical recovery was shorter among patients who received HCQ, but this difference did not reach statistical significance. CONCLUSION: Most of the patients with COVID-19 presented with mild disease and exhibited a clinical trajectory not similar to other countries. Outcomes did not differ by HCQ treatment status in line with other concluded studies on the benefit of using HCQ in the treatment of COVID-19.

Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study.

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. RESULTS: From the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5'UTR 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. Furthermore, rs17860048 in the Cyclophillin A promoter 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. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.

Chronic Obstructive Pulmonary Disease Prevalence and Associated Factors in a Setting of Well-Controlled HIV, A Cross-Sectional Study.

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 FEV1/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/mm3 (IQR 346-663 cells/mm3) and 335 cells/mm3 (IQR 187-523 cells/mm3) 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, CD4+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.

The role of epigenetics in respiratory health in urban populations in low and middle-income countries.

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.

Knowledge and use of family planning among men in rural Uganda.

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 < 10%). About half of all men reported ever using a family planning method (53%), and 40% reported current use. CONCLUSIONS: This study's quantitative results build on those of recent qualitative studies and provide information about the types of family planning information men are lacking and avenues for getting this information to them.

Brief Report: Identification of Elite and Viremic Controllers From a Large Urban HIV Ambulatory Center in Kampala, Uganda.

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 <2000 copies per milliliter for at least 6 months. RESULTS: We report a prevalence of 0.26% (38/14,492) of HIV controllers in the clinic. We identified 36 ECs and 2 VCs. These individuals were middle-aged with an average CD4 count of 858 ± 172 (mean ± SD, 95% confidence interval: 795 to 921). Their average duration in HIV care was 7.4 ± 2.1 years (mean ± SD, 95% confidence interval: 6.6 to 8.1). The majority of EC/VCs were women (87%, 33/38), reflecting the demographics of the urban clinic. CONCLUSIONS: For the first time, this study demonstrates the frequency of EC/VCs in a large urban clinic in Uganda. Further study of these East African subjects may provide insights into how some individuals are able to control HIV in the absence of medications.