High or low bodyweight appeared to be a risk factor for heightened systemic inflammation among HIV patients initiating ART, according to a recent substudy 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.
Inflammation decreases lessened among overweight, underweight patients
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 United States. Those who were overweight or obese were more often older, and underweight participants had lower hemoglobin 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.”
Weight gain beneficial for some patients on ART
Previous data have shown weight gain to be beneficial for normal or underweight patients initiating ART.
Amy C. Justice
Amy C. Justice, MD, PhD, 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 counseled to engage in healthy diet and exercise behavior.” – by Dave Muoio
Disclosure: The researchers report no relevant financial disclosures.