Amanda L. Willig

Multimorbidity Patterns in HIV-Infected Patients: The Role of Obesity in Chronic Disease Clustering

Background:Increases in multimorbidity and obesity have been noted in HIV-infected populations in the current treatment era. Patterns of multimorbid disease clustering and the impact of obesity on multimorbidity are understudied in this population. Methods:We examined obesity and multimorbidity patterns among 1844 HIV-infected patients in the UAB 1917 Clinic. Exploratory factor analysis was used to identify the underlying factor structure responsible for clustering. Patterns among the resulting morbidity factors by body mass index (BMI) category were explored. Multivariable logistic regression models were fit to identify predictors of multimorbidity cluster patterns. Results:The prevalence of multimorbidity was 65% (1205/1844). Prevalence increased with progressive BMI categories from underweight (64%) to obese (79%). Three multimorbidity clusters were identified: “metabolic,” including hypertension, gout, diabetes mellitus, and chronic kidney disease (range, 0.41–0.84; P < 0.001); “Behavioral,” including mood disorders, dyslipidemia, chronic obstructive pulmonary disease, chronic ulcer disease, osteoarthritis, obstructive sleep apnea, and cardiac disorders (range, 0.32–0.57; P < 0.001); “Substance Use,” including alcohol abuse, substance abuse, tobacco abuse, and hepatitis C (range, 0.53–0.89; P < 0.001). Obesity was associated with increased odds of multimorbidity (obese vs. normal BMI category: OR = 1.52, 95% CI: 1.15 to 2.00). Conclusions:Three patterns of disease clustering were identified. Obesity was associated with a higher likelihood of multimorbidity. The management of multimorbidity and obesity will need to be addressed in future clinical practice guidelines to enhance long-term outcomes of HIV-infected patients in the current treatment era.

Parental feeding practices and socioeconomic status are associated with child adiposity in a multi-ethnic sample of children

Parental feeding practices have been associated with childrens weight status, but results have been inconsistent across populations. Research is needed to elucidate the relationship between parental feeding practices and adiposity in diverse populations. The present study tested if: (1) parental feeding practices differed by race/ethnicity, (2) parental pressure to eat and parental restriction were associated with adiposity levels, and (3) to investigate the relationship between parental feeding practices and/or child adiposity with socioeconomic status (SES). Structural equations modeling was conducted to test the model in 267 children aged 7-12 years self-identified as African American (AA), European American (EA), or Hispanic American (HA) from economically diverse backgrounds. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Parental restriction was a significant predictor of child adiposity while parental pressure to eat had an inverse relationship with child adiposity. HA parents reported significantly higher levels of restriction and pressure to eat, whereas EA parents reported the lowest. SES was positively associated with child adiposity and inversely related to parental restriction and pressure to eat. Thus, parental feeding practices differ across racial/ethnic groups and SES and may contribute to population differences in child adiposity.

HIV infection and obesity: Where did all the wasting go?

BACKGROUND The success of antiretroviral therapy (ART) has led to dramatic changes in causes of morbidity and mortality in HIV-infected individuals. As chronic diseases rates have increased in HIV+ populations, modifiable risk factors such as obesity have increased in importance. Our objective was to evaluate factors associated with weight change among patients receiving ART. METHODS ART-naïve patients initiating therapy at the University of Alabama - Birmingham 1917 HIV/AIDS Clinic from 2000- 2008 were included. Body Mass Index (BMI) was categorized as: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9) and obese (≥30). Linear regression models were used to evaluate overall change in BMI and factors associated with increased BMI category 24 months following ART initiation. RESULTS Among 681 patients, the mean baseline BMI was 25.4 ± 6.1; 44% of patients were overweight/obese. At 24 months, 20% of patients moved from normal to overweight/obese or overweight to obese BMI categories. Greater increases in BMI were observed in patients with baseline CD4 count < 50 cells/µl (3.4 ± 4.1, P<0.01) and boosted protease inhibitor use (2.5±4.1 P=0.01), but did not account for all of the variation observed in weight change. CONCLUSIONS The findings that almost half of patients were overweight or obese at ART initiation, and 1 in 5 patients moved to a deleterious BMI category within 2 years of ART initiation are alarming. ART therapy provides only a modest contribution to weight gain in patients. Obesity represents a highly prevalent condition in patients with HIV infection and an important target for intervention.

Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada.

The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m(2) between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ≥30 kg/m(2)) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9 kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future.

African genetic admixture is associated with body composition and fat distribution in a cross-sectional study of children

Objective:Although differences in body composition parameters among African American (AA), Hispanic American (HA) and European American (EA) children are well documented, the factors underlying these differences are not completely understood. Environmental and genetic contributors have been evaluated as contributors to observed differences. This study evaluated the extent to which African or European ancestral genetic background influenced body composition and fat distribution in 301 peripubertal AA (n=107), HA (n=79) and EA (n=115) children aged 7–12.Design:Estimates of African admixture (AFADM) and European admixture (EUADM) were obtained for every subject using 142 ancestry informative DNA markers. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Multiple regression models were conducted to evaluate the contribution of admixture estimates to body composition and fat distribution.Results:Greater AFADM was associated with lower fat mass (P=0.0163), lower total abdominal adipose tissue (P=0.0006), lower intra-abdominal adipose tissue (P=0.0035), lower subcutaneous abdominal adipose tissue (P=0.0115) and higher bone mineral content (BMC) (P=0.0253), after adjusting for socio-economic status, sex, age, height, race/ethnicity and pubertal status. Greater EUADM was associated with lower lean mass (LM) (P=0.0056).Conclusion:These results demonstrate that ancestral genetic background contributes to racial/ethnic differences in body composition above and beyond the effects of racial/ethnic classification and suggest a genetic contribution to total body fat accumulation, abdominal adiposity, LM and BMC.

Genetic admixture, social–behavioural factors and body composition are associated with blood pressure differently by racial–ethnic group among children

Cardiovascular disease has a progressively earlier age of onset, and disproportionately affects African Americans (AAs) in the United States. It has been difficult to establish the extent to which group differences are due to physiological, genetic, social or behavioural factors. In this study, we examined the association between blood pressure and these factors among a sample of 294 children, identified as AA, European American or Hispanic American. We use body composition, behavioural (diet and physical activity) and survey-based measures (socio-economic status and perceived racial discrimination), as well as genetic admixture based on 142 ancestry informative markers (AIMs) to examine associations with systolic and diastolic blood pressure. We find that associations differ by ethnic/racial group. Notably, among AAs, physical activity and perceived racial discrimination, but not African genetic admixture, are associated with blood pressure, while the association between blood pressure and body fat is nearly absent. We find an association between blood pressure and an AIM near a marker identified by a recent genome-wide association study. Our findings shed light on the differences in risk factors for elevated blood pressure among ethnic/racial groups, and the importance of including social and behavioural measures to grasp the full genetic/environmental aetiology of disparities in blood pressure.

Higher Time-updated Body Mass Index: Association with Improved CD4+ Cell Recovery on HIV Treatment

Background:Prior studies found overweight or obese HIV-infected individuals had greater early CD4+ cell recovery on antiretroviral therapy (ART), but the results have been inconsistent. We assessed the longitudinal relationship between body mass index (BMI) and CD4+ cell recovery on ART in a large, multisite cohort to identify potential physiologic links between adiposity and CD4+ cell expansion. Methods:We modeled the relationship of time-updated BMI with CD4+ count in patients starting ART from 17 North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) cohorts. The primary analysis used a linear mixed effects model incorporating up to 13 years of data per patient and adjusted for age, sex, race, ART regimen, baseline CD4+ count and other covariates. Sensitivity analyses limited the cohort to patients with sustained viral suppression or censored at virologic failure. Results:Fourteen thousand eighty-four HIV-infected individuals initiating ART contributed data between 1998 and 2010. Time-updated BMI was significantly associated with CD4+ cell recovery over time (P < 0.001). After 5 years of ART, the mean CD4+ count at a BMI of 30 kg/m2 was 22% higher than at a BMI of 22 kg/m2 (606 vs. 498 cells per microliter) and 34% higher at a BMI of 40 kg/m2 (665 vs. 498 cells per microliter). Results were similar in the sensitivity analyses. Discussion:Higher BMI is associated with long-term advantages in immune recovery on ART. Although it is unclear if this impacts health outcomes, including balancing the negative health effects of obesity, elucidating the underlying mechanism could identify therapies for patients with suboptimal immune reconstitution.

Body fat and racial genetic admixture are associated with aerobic fitness levels in a multiethnic pediatric population.

Aerobic fitness and adiposity are each independently associated with health outcomes among children, although the relationship between these two variables is unclear. Our objectives were to evaluate (i) the association of adiposity with aerobic fitness using objectively measured levels of percent body fat, compared to BMI as a percentile proxy for adiposity while controlling for genetic admixture, and (ii) the congruence of BMI categories with high and low body fat categories of objectively measured percent body fat. Participants were 232 African‐American (AA), European‐American (EA), and Hispanic‐American (HA) children aged 7–12 years (Tanner stage <3). Aerobic fitness was measured via a submaximal indirect calorimetry treadmill test (VO2–170), and physical activity levels with accelerometry. Genetic admixture estimates were obtained using 140 genetic ancestry informative markers to estimate European, African, and Amerindian admixture. Fat mass was determined using dual‐energy x‐ray absorptiometry (DXA). Children were classified into a low body fat group (<25% in males, <30% in females) or a high body fat group based on their percent body fat; children were also categorized according to BMI percentile. Children in the low body fat group had significantly higher aerobic fitness (P < 0.05) regardless of BMI percentile classification. Higher African genetic admixture was associated with lower aerobic fitness (P < 0.05), while physical activity was positively associated with fitness (P < 0.01). In conclusion, aerobic fitness levels differ by percent body fat and genetic admixture irrespective of BMI classification, and such differences should be taken into account when evaluating outcomes of health interventions.

Adjusting Adiposity and Body Weight Measurements for Height Alters the Relationship With Blood Pressure in Children

BACKGROUND Adiposity measures are associated with increased pediatric blood pressure (BP). However, this correlation can be confounded by the relationship of both variables to height. We evaluated whether adiposity and anthropometric measures were associated with pediatric BP before and after adjusting each value for height. METHODS Participants included 281 African-American (AA), European-American (EA), and Hispanic-American (HA) children aged 7-12 years. BP percentiles were calculated according to pediatric guidelines using the average of four measurements. Total fat mass was determined using dual-energy X-ray absorptiometry. Socioeconomic status (SES) was calculated with the Hollingshead index. Adiposity measures were indexed for height using log-log regression analysis. Partial correlations identified measures associated with BP. Linear regression was used to test the association of those measures with absolute BP, whereas logistic regression was used to evaluate the odds for hypertension. RESULTS More AAs (16.3%) presented with potential hypertension than EA (5.1%) or HA (2.7%) children. After adjusting for covariates, fat mass, body mass index, and waist circumference were positively significantly associated with absolute BP and hypertension in AA and EA children (P < 0.05). When these measures were height-indexed, only waist remained significantly positively associated with hypertension risk in these two groups. No measures were significantly associated with BP among HA children. CONCLUSIONS In this multiethnic pediatric population, waist circumference was the strongest significant adiposity predictor of hypertension risk among AA and EA children. Additional research is needed to determine which environmental and genetic factors contribute to pediatric hypertension, particularly among HA groups.

Body mass index and early CD4 T‐cell recovery among adults initiating antiretroviral therapy in North America, 1998–2010

Adipose tissue affects several aspects of the cellular immune system, but prior epidemiological studies have differed on whether a higher body mass index (BMI) promotes CD4 T‐cell recovery on antiretroviral therapy (ART). The objective of this analysis was to assess the relationship between BMI at ART initiation and early changes in CD4 T‐cell count.