NRU :: Browsing by Author "Siedner, Mark J."

Browsing by Author "Siedner, Mark J."

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Adverse childhood experiences and adult cardiometabolic risk factors and disease outcomes: Cross-sectional, populationbased study of adults in rural Uganda
(Journal of global health, 2021) Wooyoung Kim, Andrew; Kakuhikire, Bernard; Baguma, Charles; North, Crystal M.; Satinsky, Emily N.; Perkins, Jessica M.; Ayebare, Patience; Kiconco, Allen; Namara, Elizabeth B.; Bangsberg, David R.; Siedner, Mark J.
Cardiovascular diseases (CVD) pose a major threat to public health in sub-Saharan African communities, where the burden of these classes of illnesses is expected to double by 2030. Growing research suggests that past developmental experiences and early life conditions may also elevate CVD risk throughout the life course. Greater childhood stress and adversity are consistently associated with a range of adult CVDs and associated risk factors, yet little research exists on the long-term effects of early life stress on adult physical health outcomes, especially CVD risk, in sub-Saharan African contexts. This study aims to evaluate the associations between adverse childhood experiences and adult cardiometabolic risk factors and health outcomes in a population-based study of adults living in Mbarara, a rural region of southwestern Uganda.
ART adherence and viral suppression are high among most non-pregnant individuals with early-stage, asymptomatic HIV infection: an observational study from Uganda and South Africa
(Journal of the International AIDS Society, 2019) Haberer, Jessica E.; Bwana, Bosco M.; Orrell, Catherine; Asiimwe, Stephen; Amanyire, Gideon; Musinguzi, Nicholas; Siedner, Mark J.; Matthews, Lynn T.; Tsai, Alexander C.; Katz, Ingrid T.; Bell, Kathleen; Kembabazi, Annet; Mugisha, Stephen; Kibirige, Victoria; Cross, Anna; Kelly, Nicola; Hedt-Gauthier, Bethany; Bangsberg, David R.
The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS-free generation depend on high adherence in individuals initiating ART during early-stage HIV infection; however, adherence may be difficult in the absence of illness and associated support. From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non-pregnant women with early-stage HIV infection (CD4 > 350 cells/lL), pregnant women with early-stage HIV infection and men and non-pregnant women with late-stage HIV infection (CD4 < 200 cells/lL). Socio-behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically. Adherence data were available for 869 participants: 322 (37%) early/non-pregnant, 199 (23%) early/pregnant and 348 (40%) late/non-pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non-pregnant versus early/pregnant or late/non-pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non-pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking. ART adherence among non-pregnant individuals with early-stage infection is as high or higher than with late-stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late-stage infection in South Africa and highlight the need for differentiated care delivery.
Blood pressure trajectories and the mediated effects of body mass index and HIV‐related inflammation in a mixed cohort of people with and without HIV in rural Uganda
(The Journal of Clinical Hypertension, 2019) Okello, Samson; Kim, June‐Ho; Sentongo, Ruth N.; Tracy, Russell; Tsai, Alexander C.; Kakuhikire, Bernard; Siedner, Mark J.
We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV‐infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex‐ and age‐quartilematched, population‐based, HIV‐uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high‐sensitivity C‐reactive protein and interleukin‐ 6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two‐stage parametric regression models. Overall HIV‐uninfected participants had higher mean BP than HIV‐infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIVuninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV‐related biomarkers. Over four years of observation, HIV‐infected people in rural Uganda have lower BP than HIV‐uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV‐associated inflammation, explained a majority of the difference in BP observed.
Coronary artery calcium, HIV and inflammation in Uganda compared with the USA
(Open Heart, 2019) Alencherry, Ben; Erem, Geoffrey; Mirembe, Grace; Ssinabulya, Isaac; Yun, Chun-Ho; Hung, Chung-Lieh; Siedner, Mark J.; Bittencourt, Marcio; Kityo, Cissy; McComsey, Grace A.; Longenecker, Chris T.
To compare the prevalence of detectable coronary artery calcium (CAC) among higher risk, older people living with HIV (PLWH) and uninfected persons in Uganda versus the USA, and second to explore associations of CAC with HIV-specific variables and biomarkers of inflammation. This cross-sectional study of 430 total subjects compared 100 PLWH on antiretroviral therapy and 100 age-matched and sex-matched HIV-uninfected controls in Uganda with 167 PLWH on antiretroviral therapy and 63 uninfected controls in the USA. Multivariable logistic regression was used to examine associations with detectable CAC (CAC >0). Compared with US subjects, Ugandans were older (mean age 56 vs 52 years) and were more likely to have diabetes (36% vs 3%) and hypertension (85% vs 36%), but were less likely to be male (38% vs 74%) or smokers (4% vs 56%). After adjustment for HIV serostatus, age, sex and traditional risk factors, Ugandans had substantially lower odds of CAC >0 (adjusted OR 0.07 (95% CI 0.03 to 0.17), p<0.001). HIV was not associated with CAC >0 in either country (p>0.1). Among all PLWH, nadir CD4 count was associated with the presence of CAC, and among Ugandans soluble intercellular adhesion molecule (p=0.044), soluble CD163 (p=0.004) and oxidised low-density lipoprotein (p=0.043) were all associated with the presence of CAC. Ugandans had a dramatically lower prevalence of any coronary calcification compared with US subjects. The role of HIV infection and inflammation as risk factors for subclinical coronary disease in sub-Saharan Africa merits further investigation.
Disinhibition in Risky Sexual Behavior in Men, but Not Women, during Four Years of Antiretroviral Therapy in Rural, Southwestern Uganda
(PLoS One, 2013) Kembabazi, Annet; Bajunirwe, Francis; Hunt, Peter W.; Martin, Jeffrey N.; Muzoora, Conrad; Haberer, Jessica E.; Bangsberg, David R.; Siedner, Mark J.
In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy.We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count.506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29–39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74–0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14–1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92–1.67, p = 0.16).Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.
Electrocardiographic Evidence of Cardiac Disease by Sex and HIV Serostatus in Mbarara, Uganda
(Global heart, 2019) Kentoffio, Katie; Albano, Alfred; Koplan, Bruce; Feng, Maggie; Muthalaly, Rahul G.; Campbell, Jeffrey I.; Sentongo, Ruth; Tracy, Russell P.; Peck, Robert; Okello, Samson; Tsai, Alexander C.; Siedner, Mark J.
Numerous studies in the United States and Europe have demonstrated an increased risk for cardiovascular disease (CVD) among persons living with HIV (PLWH).[1] The relationship between HIV and subsequent CVD has not been as well-established in sub-Saharan Africa (SSA). PLWH in SSA have a high burden of untreated risk factors, but results vary regarding surrogate markers of CVD. Data on outcomes, such as stroke or myocardial infarction, are limited. An analysis of data from the SMART trial found that PLWH had a high prevalence of ECG abnormalities at baseline, which predicted CVD risk over the study period.[2] We investigated the prevalence of ECG abnormalities by HIV serostatus in rural Uganda to estimate differences in CVD risk. As secondary aims, we assessed a) ECG evidence of ischemic coronary artery disease by HIV serostatus and b) sex-based differences in ECG findings.
High prevalence of prolonged QTc interval among individuals in ambulatory diabetic care in southwestern Uganda
(International journal of diabetes in developing countries, 2021) Migisha, Richard; Agaba, David Collins; Katamba, Godfrey; Miranda, Silvia Lopez; Muyingo, Anthony; Siedner, Mark J.
Heart rate-corrected QT (QTc) interval is associated with increased risk for cardiovascular events and mortality among individuals with diabetes mellitus (DM). Little is known about the epidemiology of prolonged QTc among people with DM in resource-limited settings. Methods We conducted a cross-sectional study among adults with diabetes in ambulatory care at the Mbarara Regional Referral Hospital, from November 2018 to April 2019. Twelve-lead ECG recordings were performed on all participants. We collected clinical and laboratory data related to diabetes disease status and treatment control.We estimated QTc using Bazett’s formula and categorized it according to standardized sex-adjusted thresholds. Linear regression analysis was performed to identify correlates of QTc. Results We recruited 299 participants with a mean age of 50.1 years (SD±9.8) and mean HbA1c of 9.7 % (SD±2.6), and 69.6% were female. We detected prolonged and borderline QTc in 6.4% (19/299, 95% CI: 3.9–9.7%) and 23.4% (70/299, 95% CI: 18.7–28.6%) of participants, respectively. In multivariate models, factors associated with increasing QTc interval were mean arterial pressure (β=0.34; 95% CI: 0.07–0.63, p=0.019) and female sex (β=15.26; 95% CI: 7.58–22.94, p<0.001). Conclusions The prevalence of abnormal QTc among individuals in routine diabetes care in southwestern Uganda was high. Female sex and mean arterial pressure were correlated with QTc interval. Given these findings, future studies should explore the clinical impact of abnormal QTc in this patient population.
HIV infection, pulmonary tuberculosis and COPD in rural Uganda: A cross-sectional study
(Lung, 2018) North, Crystal M.; Allen, Joseph G.; Okello, Samson; Sentongo, Ruth; Kakuhikire, Bernard; Ryan, Edward T.; Tsai, Alexander C.; Christiani, David C.; Siedner, Mark J.
HIV is associated with chronic obstructive pulmonary disease (COPD) in high resource settings. Similar relationships are less understood in low resource settings. We aimed to estimate the association between HIV infection, tuberculosis and COPD in rural Uganda. Methods: The Uganda Non-Communicable Diseases and Aging Cohort study observes people 40 years and older living with HIV (PLWH) on antiretroviral therapy, and population-based HIV-uninfected controls in rural Uganda. Participants completed respiratory questionnaires and post-bronchodilator spirometry. Results: Among 269 participants with spirometry, median age was 52 (IQR 48–55), 48% (n=130) were ever-smokers, and few (3%, n=9) reported a history of COPD or asthma. All participants with prior tuberculosis (7%, n=18) were PLWH. Among 143 (53%) PLWH, median CD4 count was 477 cells/mm3 and 131 (92%) were virologically suppressed. FEV1 was lower among older individuals (−0.5 %pred/year, 95% CI 0.2–0.8, p<0.01) and those with a history of tuberculosis (−14.4 %pred, 95% CI −23.5 - −5.3, p < 0.01). COPD was diagnosed in 9 (4%) participants, eight of whom (89%) were PLWH, 6 of whom (67%) had a history of tuberculosis, and all of whom (100%) were men. Among 287 participants with complete symptom questionnaires, respiratory symptoms were more likely among women (AOR 3.9, 95% CI 2.0–7.7, p<0.001) and those in homes cooking with charcoal (AOR 3.2, 95% CI 1.4–7.4, p=0.008).
Ideal Cardiovascular Health and Carotid Atherosclerosis in a Mixed Cohort of HIV-Infected and Uninfected Ugandans
(AIDS research and human retroviruses, 2017) Feinstein, Matthew J.; Kim, June-Ho; Bibangambah, Prossy; Sentongo, Ruth; Martin, Jeffrey N.; Tsai, Alexander C.; Bangsberg, David R.; Hemphill, Linda; Triant, Virginia A.; Boum II, Yap; Hunt, Peter W.; Okello, Samson; Siedner, Mark J.
Preventable cardiovascular disease (CVD) risk factors are responsible for the majority of CVD-related deaths, and are increasingly recognized as a cause of morbidity and mortality for HIV-infected persons taking antiretroviral therapy (ART). Simplified tools such as the American Heart Association’s ideal cardiovascular health (iCVH) construct may identify and prognosticate CVD risk in resource-limited settings. No studies have evaluated iCVH metrics in sub-Saharan Africa or among HIV-infected adults. Thus, the central aim of this study was to compare levels of iCVH metrics and their correlations with carotid atherosclerosis for HIV-infected adults versus uninfected controls in a well-phenotyped Ugandan cohort. We analyzed the prevalence of iCVH metrics in a mixed cohort of HIV-infected persons on stable ART and uninfected, population-based comparators in Mbarara, Uganda. We also assessed the validity of iCVH by correlating iCVH values with common carotid intima media thickness (CCIMT). HIV-infected persons had a mean of 4.9 (SD 1.1) iCVH metrics at ideal levels versus 4.3 (SD 1.2) for uninfected controls ( p = .002). This difference was largely driven by differences in blood pressure, blood glucose, and diet. In multivariable-adjusted linear regression models, each additional iCVH metric at an ideal level was associated with a significant 0.024mm decrease in CCIMT ( p < .001).HIV-infected persons on ART in rural Uganda had more iCVH metrics at ideal levels than uninfected persons. The difference appeared driven by factors that are putatively influenced by access to routine medical care. Composite scores of iCVH metrics were associated with subclinical atherosclerosis and more predictive of atherosclerosis for uninfected persons.
Increasing Prevalence of HIV Pretreatment Drug Resistance in Women But Not Men in Rural Uganda During 2005–2013
(AIDS patient care and STDs, 2018) McCluskey, Suzanne M.; Lee, Guinevere Q.; Kamelian, Kimia; Kembabazi, Annet; Musinguzi, Nicholas; Bwana, Mwebesa B.; Muzoora, Conrad; Haberer, Jessica E.; Hunt, Peter W.; Martin, Jeffrey N.; Boum, Yap; Bangsberg, David R.; Harrigan, Richard; Siedner, Mark J.
The prevalence of HIV pretreatment drug resistance (PDR) is increasing in sub-SaharanAfrica.We sought to describe correlates of PDR and evaluate effects of PDR on clinical outcomes in rural Uganda. We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, a cohort of antiretroviral therapy (ART)-naive adults with HIV (2005–2015). We performed resistance testing on pre-ART specimens. We defined PDR as any World Health Organization (WHO) 2009 surveillance drug resistance mutation and classified PDR level using the Stanford algorithm. We fit unadjusted and sex-stratified log binomial regression and Cox proportional hazardmodels to identify correlates of PDR and the impact of PDR on viral suppression, loss to follow-up (LTFU), and death. We analyzed data from 738 participants (median age 33 years, 69% female). Overall, prevalence of PDR was 3.5% (n = 26), owing mostly to resistance to non-nucleoside reverse transcriptase inhibitors. PDR increased over time in women (1.8% in those enrolling in clinic in 2001–2006, vs. 7.0% in 2007–2013; p = 0.006), but not in men (1.15% vs. 0.72%, p = 0.737). Lower pre-ART log10 HIV RNA was also associated with higher prevalence of PDR. We identified longer time to viral suppression among those with PDR compared with without PDR (0.5 and 0.3 years, respectively, p = 0.023), but there was no significant relationship with mortality or LTFU ( p = 0.139). We observed increasing rates of PDR in women in southwestern Uganda. Implications of this trend, particularly to prevention of mother-to-child transmission programs in the region, require attention due to delayed viral suppression among those with PDR.
Internalized stigma, depressive symptoms, and the modifying role of antiretroviral therapy: A cohort study in rural Uganda
(SSM-Mental Health, 2021) Bebell, Lisa M.; Kembabazi, Annet; Musinguzi, Nicholas; Martin, Jeffrey N.; Hunt, Peter W.; Boum, Yap; O'Laughlin, Kelli N.; Muzoora, Conrad; Haberer, Jessica E.; Mwebesa, Bosco Bwana; Bangsberg, David R.; Siedner, Mark J.; Tsai, Alexander C.
Depression affects over 40% of people with HIV (PHIV) in low- and middle-income countries, and over half of PHIV report HIV related internalized stigma. However, few longitudinal studies of PHIV have examined the relationship between HIV-related stigma and depression. Data were analyzed from the 2007-15 Uganda AIDS Rural Treatment Outcomes (UARTO) Study, a cohort of 454 antiretroviral therapy (ART)-naïve PHIV (68% women) starting ART. Our primary outcome was depression symptom severity over the first two years of ART, measured using a locally adapted version of the Hopkins Symptom Checklist; our primary exposure was the 6-item Internalized AIDS-Related Stigma Scale. Both scores were measured at enrollment and at quarterly follow-up visits. We fit linear generalized estimating equations (GEE) regression models to estimate the association between stigma and depression symptom severity, adjusting for potential confounders. We included a stigma timeproduct term to assess the modifying effect of ART on the association between internalized stigma and depression symptom severity. UARTO participants had a median age of 32 years and median enrollment CD4 count of 217 cells/mm3. Both depression symptom severity and internalized stigma declined on ART, particularly during the first treatment year. In multivariable regression models, depression symptom severity was positively associated with internalized stigma (b ¼ 0.03; 95% confidence interval [CI], 0.02 to 0.04) and negatively associated with ART duration >6 months (b ¼ 0.16; 95% CI, 0.19 to 0.13). The estimated product term coefficient was negative and statistically significant (P ¼ 0.004), suggesting that the association between internalized stigma and depression symptom severity weakened over time on ART. Thus, in this large cohort of PHIV initiating ART in rural Uganda, depression symptom severity was associated with internalized stigma but the association declined with time on ART. These findings underscore the potential value of ART as a stigma reduction intervention for PHIV, particularly during early treatment.
Low population prevalence of atrial fibrillation in rural Uganda: A community-based cross-sectional study
(International journal of cardiology, 2018) Muthalaly, Rahul G.; Koplan, Bruce A.; Albano, Alfred; North, Crystal; Campbell, Jeffrey I.; Kakuhikire, Bernard; Vořechovská, Dagmar; Kraemer, John D.; Tsai, Alexander C.; Siedner, Mark J.
Atrial fibrillation (AF) is a major risk factor for stroke, which is the leading cause of cardiovascular mortality in sub-Saharan Africa. However, there is limited population-based epidemiological data on AF in sub-Saharan Africa. We sought to estimate the prevalence and correlates of AF in rural Uganda.We conducted a cross-sectional study using community health fairs in 2015 targeting eight villages in rural Uganda. Study participants completed a medical history, a clinical exam, blood collection, and 12‑lead electrocardiographic (ECG) screening. Of 1814 participants enrolled in a parent cohort study that includes 98% of adults residing in the geographic area, 856 attended a health fair and were included in this study. Our primary outcome was AF or atrial flutter. We modelled population prevalence of the outcome with inverse probability of treatment weighting using data collected from the full population.856 (47.2%) adults in the area attended a health fair and were included in the analysis. Health fair attendees were older (42 vs 34 years, P < 0.0001), in worse self-reported health (P < 0.0001) and more likely to be female (62% vs 49%, P < 0. 0001) compared with non-attendees. After applying weights, the estimated population mean age was 37.7 ± 14.9 years. 15% of the population was overweight or obese and 1.9% had left atrial enlargement on ECG. Despite this, the weighted estimate of AF was 0% (95%CI 0–0.54%).AF appears less prevalent in rural Uganda than in developed countries. The explanations for this finding may be genetic, environmental or related to survivorship bias.
Lung function and atherosclerosis: a cross‑sectional study of multimorbidity in rural Uganda
(BMC pulmonary medicine, 2022) Gilbert, Rebecca F.; Cichowitz, Cody; Bibangambah, Prossy; Kim, June‑Ho; Hemphill, Linda C.; Yang, Isabelle T.; Sentongo, Ruth N.; Kakuhikire, Bernard; Christiani, David C.; Tsai, Alexander C.; Okello, Samson; Siedner, Mark J.; North, Crystal M.
Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. Methods: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. Results: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (β = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. Conclusions: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.
Postural changes in blood pressure among patients with diabetes attending a referral hospital in southwestern Uganda: a cross‑sectional study
(BMC Cardiovascular Disorders, 2021) Migisha, Richard; Agaba, David Collins; Katamba, Godfrey; Manne‑Goehler, Jennifer; Muyingo, Anthony; Siedner, Mark J.
Orthostatic hypotension (OH) and orthostatic hypertension (OHT) are often unrecognized in clinical care for diabetic individuals, yet they are associated with increased risk for adverse cardiovascular outcomes. We aimed to determine the prevalence of the abnormal orthostatic blood pressure (BP) responses, and associated factors among diabetic individuals in ambulatory care for diabetes in southwestern Uganda. Methods: We conducted a cross-sectional study among diabetic individuals aged 18–65 years at Mbarara Regional Referral Hospital, southwestern Uganda from November 2018 to April 2019. We obtained demographic and clinical data including a detailed medical history, and glycemic profile. BP measurements were taken in supine position and within 3 min of standing. We defined OH in participants with either ≥ 20 mmHg drop in systolic BP (SBP) or ≥ 10 mmHg drop in diastolic BP (DBP) after assuming an upright position. OHT was defined in participants with either a ≥ 20 mmHg rise in SBP, or ≥ 10 mmHg rise in DBP after assuming an upright position. Multivariate logistic regression was used to identify factors associated with OH and OHT. Results: We enrolled 299 participants, with a mean age of 50 years (SD ± 9.8), and mean HbA1c of 9.7% (SD ± 2.6); 70% were female. Of the 299 participants, 52 (17.4%; 95% CI 13.3–22.2%) met the definition of OH and 43 (14.4%; 95% CI 10.6–18.9%) were classified as having OHT. In multivariable models, factors associated with diabetic OH were older age (OR = 2.40 for 51–65 years vs 18–50 years, 95% CI 1.02–5.67, P = 0.046), diabetic retinopathy (OR = 2.51; 95% CI 1.14–5.53, P = 0.022), higher resting SBP ≥ 140 mmHg (OR = 3.14; 95% CI 1.31–8.7.56, P = 0.011), and history of palpitations (OR = 2.31; 95% CI 1.08–4.92, P = 0.031). Self-report of palpitations (OR = 3.14; 95% CI 1.42–6.95, P = 0.005), and higher resting SBP ≥ 140 mmHg (OR = 22.01; 95% CI 1.10–4.42, P = 0.043) were associated with OHT. Conclusion: OH and OHT are common among diabetic individuals in ambulatory diabetes care in southwestern Uganda. Orthostatic BP measurements should be considered as part of routine physical examination to improve detection of OH and OHT, especially among older diabetics with complications of the disease. Future studies to assess the health and prognostic implications of OH and OHT among diabetics in the region are warranted.
Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study
(Global Heart, 2020) Migisha, Richard; Agaba, David Collins; Katamba, Godfrey; Kwaga, Teddy; Tumwesigye, Raymond; Miranda, Silvia Lopez; Muyingo, Anthony; Siedner, Mark J.
Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa. Objectives: To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda. Method: We conducted a cross-sectional study among adults with diabetes from November 2018 to April 2019. CAN was assessed using the five autonomic function tests: deep breathing, Valsalva maneuver, postural index on standing, change in blood pressure during standing and diastolic blood pressure response to isometric exercise. We estimated the prevalence of CAN and fit regression models to identify its demographic and clinical correlates. Results: We enrolled 299 individuals. The mean age was 50.1 years (SD ± 9.8), mean HbA1c was 9.7 (SD ± 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 –8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 –9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 –4.34, p = 0.016) were correlated with CAN. Conclusions: Our findings reveal a high prevalence of CAN among individuals in routine outpatient care for diabetes mellitus in Uganda. Older age, longer duration of diabetes and coexistence of retinopathy are associated with CAN. Future work should explore the clinical significance and long term outcomes associated with CAN in this region.
Prevalence and correlates of carotid plaque in a mixed HIV‑serostatus cohort in Uganda
(BMC Cardiovascular Disorders, 2021) Bibangambah, Prossy; Hemphill, Linda C.; Acan, Moses; Tsai, Alexander C.; Sentongo, Ruth N.; Kim, June‑Ho; Yang, Isabelle T.; Siedner, Mark J.; Okello, Samson
The extent to which the risk of atherosclerotic cardiovascular disease (ACVD) is increased among people living with HIV (PLWH) in sub-Saharan Africa remains unknown. Setting: Cross-sectional analysis nested within the Ugandan Noncommunicable Diseases and Aging Cohort, including PLWH in rural Uganda > 40 years taking antiretroviral therapy (ART) for at least 3 years, and a population-based control group of HIV-uninfected age- and sex-matched persons. Methods: We conducted carotid ultrasonography and collected ACVD risk factor data. Our outcome of interest was carotid plaque, defined as > 1.5 mm thickness from the intima-lumen interface to the media-adventitia interface. We fit multivariable logistic regression models to estimate correlates of carotid plaque including HIV-specific and traditional cardiovascular risk factors. Results: We enrolled 155 (50.2%) PLWH and 154 (49.8%) HIV-uninfected comparators, with a mean age of 51.4 years. Among PLWH, the median CD4 count was 433 cells/mm3 and 97.4% were virologically suppressed. Carotid plaque prevalence was higher among PLWH (8.4% vs 3.3%). HIV infection (aOR 3.90; 95% CI 1.12–13.60) and current smokers (aOR 6.60; 95% CI 1.22–35.80) had higher odds of carotid plaque, whereas moderate (aOR 0.13, 95% CI 0.01–1.55) and vigorous intensity of physical activity (aOR 0.34, 95% CI 0.07–1.52) were associated with decreased odds of carotid plaque. Conclusion: In rural Uganda, PLWH have higher prevalence of carotid plaque compared to age- and sex-matched HIV-uninfected comparators. Future work should explore how biomedical and lifestyle modifications might reduce atherosclerotic burden among PLWH in the region.
Prevalence and correlates of chronic obstructive pulmonary disease and chronic respiratory symptoms in rural southwestern Uganda: a cross-sectional, population-based study
(Journal of global health, 2019) North, Crystal M.; Kakuhikire, Bernard; Vořechovská, Dagmar; Kigozi, Simone Hausammann; McDonough, Amy Q.; Downey, Jordan; Christiani, David C.; Tsai, Alexander C.; Siedner, Mark J.
The global burden of chronic obstructive pulmonary disease (COPD) disproportionately affects resource-limited settings such as sub-Saharan Africa (SSA), but population-based prevalence estimates in SSA are rare. We aimed to estimate the population prevalence of COPD and chronic respiratory symptoms in rural southwestern Uganda.Adults at least 18 years of age who participated in a population-wide census in rural southwestern Uganda completed respiratory questionnaires and lung function testing with bronchodilator challenge at health screening events in June 2015. We defined COPD as post-bronchodilator forced expiratory volume in one second to forced vital capacity ratio less than the lower limit of normal. We fit multivariable linear and log binomial regression models to estimate correlates of abnormal lung function and respiratory symptoms, respectively. We included inverse probability of sampling weights in models to facilitate population-level estimates.Forty-six percent of census participants (843/1814) completed respiratory questionnaires and spirometry, of which 565 (67%) met acceptability standards. COPD and respiratory symptom population prevalence were 2% (95% confidence interval (CI) = 1%-3%) and 30% (95% CI = 25%-36%), respectively. Respiratory symptoms were more prevalent and lung function was lower among women and ever-smokers (P < 0.05). HIV serostatus was associated with neither respiratory symptoms nor lung function.COPD population prevalence was low despite prevalent respiratory symptoms. This work adds to the growing body of literature depicting lower-than-expected COPD prevalence estimates in SSA and raises questions about whether the high respiratory symptom burden in rural southwestern Uganda represents underlying structural lung disease not identified by screening spirometry.
Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa
(Annals of Internal Medicine, 2021) Siedner, Mark J.; Moosa, Mahomed-Yunus S.; McCluskey, Suzanne; Gilbert, Rebecca F.; Pillay, Selvan; Aturinda, Isaac; Ard, Kevin; Muyindike, Winnie; Musinguzi, Nicholas; Masette, Godfrey; Pillay, Melendhran; Moodley, Pravikrishnen; Brijkumar, Jaysingh; Rautenberg, Tamlyn; George, Gavin; Gandhi, Rajesh T.; Johnson, Brent A.; Sunpath, Henry; Bwana, Mwebesa B.; Marconi, Vincent C.
Virologic failure in HIV remains a major public health threat in sub-Saharan Africa. It occurs in approximately 10% to 30% of patients within 2 years of antiretroviral therapy (ART) initiation and is associated with development of drug resistance, increased risk for opportunistic infections and death, and ongoing transmission of HIV (1–6). The optimal management of virologic failure is unknown. Guidelines published by the U.S. Department of Health and Human Services recommend genotypic resistance testing (GRT) to assist in the management of virologic failure (7). Small randomized trials and observational studies completed in the early ART era in the United States suggested that GRT has benefit in virologic control and selection of active regimens (8–11). However, GRT after failure of first-line therapy is not routinely supported by treatment guidelines by the World Health Organization and is not typically done in most sub-Saharan African countries (12).
Rethinking the ‘‘Pre’’ in Pre-Therapy Counseling: No Benefit of Additional Visits Prior to Therapy on Adherence or Viremia in Ugandans Initiating ARVs
(PLoS ONE, 2012) Siedner, Mark J.; Lankowski, Alexander; Haberer, Jessica E.; Kembabazi, Annet; Emenyonu, Nneka; Tsai, Alexander C.; Muzoora, Conrad; Geng, Elvin; Martin, Jeffrey N.; Bangsberg, David R.
Many guidelines recommend adherence counseling prior to initiating antiretrovirals (ARVs), however the additional benefit of pre-therapy counseling visits on early adherence is not known. We sought to assess for a benefit of adherence counseling visits prior to ARV initiation versus adherence counseling during the early treatment period. We performed a secondary analysis of data from a prospective cohort of HIV-infected patients in Mbarara, Uganda. Adults were enrolled upon initiation of ARVs. Our primary exposure of interest was ARV adherence counseling prior to initiating therapy (versus concurrent with initiation of therapy). Our outcomes of interest were: 1) average adherence .90% in first three months; 2) absence of treatment interruptions .72 hours in first three months; and 3) Viral load .400 copies/ml at the three month visit. We fit univariable and multivariable regression models, adjusted for predictors of ARV adherence, to estimate the association between additional pre-therapy counseling visits and our outcomes. Results: 300 participants had records of counseling, of whom 231 (77%) completed visits prior to initiation of ARVs and 69 (23%) on or shortly after initiation. Median age was 33, 71% were female, and median CD4 was 133 cell/ml. Median 90-day adherence was 95%. Participants who completed pre-therapy counseling visits had longer delays from ARV eligibility to initiation (median 49 vs 14 days, p,0.01). In multivariable analyses, completing adherence counseling prior to ARV initiation was not associated with average adherence .90% (AOR 0.8, 95%CI 0.4–1.5), absence of treatment gaps (AOR 0.7, 95%CI 0.2–1.9), or HIV viremia (AOR 1.1, 95%CI 0.4–3.1). Completion of adherence counseling visits prior to ARV therapy was not associated with higher adherence in this cohort of HIV-infected patients in Uganda. Because mortality and loss-to-follow-up remain high in the pre-ARV period, policy makers should reconsider whether counseling can be delivered with ARV initiation, especially in patients with advanced disease.
Sexual Relationship Power and Malnutrition Among HIV-Positive Women in Rural Uganda
(AIDS and Behavior, 2012-03-02) Siedner, Mark J.; Mukiibi, Nozmo F. B.; Emenyonu , Nneka I.; Haberer, Jessica E.; Bangsberg, David R.; Weiser, Sheri D.
Inequality within partner relationships is associated with HIV acquisition and gender violence, but little is known about more pervasive effects on women’s health. We performed a cross-sectional analysis of associations between sexual relationship power and nutritional status among women in Uganda. Participants completed questionnaires and anthropometric measurements. We assessed sexual relationship power using the Sexual Relationship Power Scale (SRPS). We performed logistic regression to test for associations between sexual relationship power and poor nutritional status including body mass index, body fat percentage, and mid-upper arm circumference. Women with higher sexual relationship power scores had decreased odds of low body mass index (OR 0.29, p = 0.01), low body fat percentage (OR 0.54, p = 0.04), and low mid-upper arm circumference (OR 0.22, p = 0.01). These relationships persisted in multivariable models adjusted for potential confounders. Targeted interventions to improve intimate partner relationship equality should be explored to improve health status among women living with HIV in rural Africa.

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