Bodyweight influences risk for inflammation mortality

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High or low bodyweight appeared to be a risk factor for heightened systemic inflammation among HIV patients initiating ART, according to a recent sub-study of the international PEARLS trial cohort.

“Although inflammatory markers tend to decrease with suppressive ART, HIV infection is also associated with chronic low-level inflammation, with several markers of inflammation or immune activation elevated even after years of therapy in comparison to HIV-uninfected populations,” the researchers wrote. “This persistent, low-grade inflammatory state, even in treated HIV infection, has been associated with an increase in multiple non-Aids comorbidities including cardiovascular disease, cancer, osteoporosis, weakness, frailty and death.”

To explore these and other previously established inflammation risks attributed to obesity and cachexia, the researchers examined data from 246 PEARLS trial participants who achieved viral suppression when initiating one of three ART regimens for the first time. These patients each demonstrated a CD4+ T-cell count fewer than 300 cells/mm3, and had no history of recent acute illness or opportunistic infection. Serum, plasma and weight were obtained and measured at zero, 24 and 48 weeks after ART initiation. For the analyses, participants were categorized as underweight, normal, overweight or obese based on BMI calculations. Areas of interest included relationships between baseline BMI or BMI change with longitudinal changes in immune activation and inflammatory markers, as well as the effect of obese BMI on these indicators.

At baseline, 8% of participants were considered underweight, 65% normal, 20% overweight and 7% obese. Underweight participants were most often from India, while more than half of the overweight or obese participants were from the US. Those who were overweight or obese were more often older, and underweight participants had lower haemoglobin and serum albumin.

Among all participants, TNF-alpha, CXCL-10 and IL-18 were significantly decreased after 48 weeks. Although most inflammatory markers were comparable between the weight groups at baseline, overweight or obese patients has a significantly lessened decrease in CRP (P = .01) while underweight participants demonstrated reduced CRP (P = .01) and IL-18 (P = .02) decreases. After adjusting analysis for demographic and clinical factors, each unit of BMI added among overweight or obese participants was associated with increased sCD14 (P = .05), but among underweight participants was associated with decreased CRP (P = .001). In addition, participants who were obese at any point during the study had greater sCD14 (P = .02).

“Although not applicable to all settings, a failure to gain weight among underweight persons may be a poor prognostic sign and signal a need for nutritional intervention, evaluation of disease progression or development of an opportunistic infection,” the researchers wrote. “In contrast, among those who are already overweight or obese, further weight gain appears to increase inflammation. Further research is needed to understand the potential barriers to weight maintenance, and test models for effective early nutritional counseling and lifestyle modifications as adjunctive therapy to ART.”

Previous data have shown weight gain to be beneficial for normal or underweight patients initiating ART.

Dr Amy C Justice, professor of medicine at Yale School of Medicine and section chief of general medicine at Veterans Affairs Connecticut Healthcare System, and colleagues evaluated weight change in the first year after ART initiation and its association with mortality in HIV-infected patients enrolled in the Veterans Aging Cohort Study. They collected data on 4,184 men and 127 women (mean age, 47.9 years) who initiated ART between 2000 and 2008. All eligible patients had weight recorded at baseline and 1 year later and were followed for another 5 years.

Among patients who were underweight at baseline, all weight gain appeared to be beneficial – gaining at least 10 pounds was associated with a significantly decreased mortality risk (HR = 0.47; 95% CI, 0.25-0.88) vs. those whose weight remained the same. In normal weight patients, survival benefits were associated with at least 10 pounds but less than 20 pounds of weight gain (HR = 0.56; 95% CI, 0.41-0.78). There was no clear benefit of weight gain, however, for overweight and obese patients, according to the researchers.

“Providers should monitor weight gain among normal and underweight patients initiating ART and examine potential reasons for failure to gain weight, including viral breakthrough, ongoing inflammation, food insecurity, drug use and intervening comorbidities,” Justice and colleagues wrote. “Overweight and obese patients can be counselled to engage in healthy diet and exercise behaviour.”

Abstract
Background: Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation in HIV is unknown.
Methods: Among a random virologically suppressed participants of the PEARLS trial, inflammatory markers were measured at weeks 0, 24, and 48 post-antiretroviral therapy (ART). Associations between baseline and change in body mass index (BMI) and inflammation changes were assessed using random effects models.
Results: Of 246 participants, 27% were overweight/obese (BMI≥25 kg/m2) and 8% were underweight (BMI Conclusion: Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation.

Abstract
Background: Weight gain after antiretroviral therapy (ART) initiation is common, but its implication for mortality is unknown. We evaluated weight change in the first year after ART initiation and its association with subsequent mortality.
Methods: Human immunodeficiency virus-infected patients from the Veterans Aging Cohort Study (VACS) who initiated ART between 2000 and 2008, with weight recorded at baseline and 1 year later, were followed another 5 years for mortality. Baseline body mass index (BMI) was classified as underweight ( Results: The sample consisted of 4184 men and 127 women with a mean age of 47.9 ± 10.0 years. After 1 year of ART, median weight change was 5.9 pounds (2.7 kg) (interquartile range, −2.9 to 17.0 pounds, −1.3 to 7.7 kg). Weight gain after ART initiation was associated with lower mortality among underweight and normal-weight patients. A minimum threshold of 10- to 19.9-pound (4.5 to 9.0 kg) weight gain was beneficial for normal-weight patients (hazard ratio, 0.56; 95% confidence interval, .41–.78), but there was no clear benefit to weight gain for overweight/obese patients. Baseline weight, CD4 cell count status, and hemoglobin level were strongly associated with weight gain. Risk for weight gain was higher among those with greater disease severity, regardless of weight at initiation.
Conclusions: The survival benefits of weight gain after ART initiation are dependent on starting BMI. Weight gain after ART is associated with lower mortality for those who are not initially overweight.

Full Healio report
Journal of Infectious Diseases abstract
Clinical Infectious Diseases abstract


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