Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia

<p>Abstract</p> <p>Background</p> <p>A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.</p> <p>Methods</p> <p>An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m²or CD4⁺lymphocyte counts of less than 50 cells/mm³, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.</p> <p>Results</p> <p>Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.</p> <p>Conclusions</p> <p>The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.</p

Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?

Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI &lt;18.5 kg/m 2 , 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; = 0.01) after adjusting for sex, age, and CD4 + lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m 2 (OR 0.96, 95% CI: 0.76 to 1.21; = 0.74). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed

Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?

Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI <18.5 kg/m2, 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; P=0.01) after adjusting for sex, age, and CD4+ lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m2 (OR 0.96, 95% CI: 0.76 to 1.21; P=0.74). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed

Adjusted hazard ratios for mortality at 12 weeks (baseline variables).

<p>There is little evidence that the association between phosphate and the hazard of death is non-linear based on a likelihood ratio test (p = 0.27). Similarly, there is little evidence that the association between any continuous variable and the hazard of death is non-linear (p>0.20 for each).</p

Study procedures and cohort status by study visit.

<p>Study procedures and cohort status by study visit.</p

Baseline participant characteristics.

<p>Abbreviations: ART, antiretroviral therapy; BMI, body mass index; BUN, blood urea nitrogen; hsCRP, high sensitivity C-reactive protein; IQR, interquartile range.</p><p>Among the 142 cases included in the multivariable analysis, values were missing for the following measurements: 8 (6%) baseline serum phosphate, 31 (22%) week one serum phosphate, 29 (20%) baseline hemoglobin (because either blood or assay reagents could not be obtained), 2 age (birth dates unknown), and one BMI (participant could not stand for height measurement).</p><p>*Normal creatinine range: females 44–80, males 53–106 µmol/L; normal albumin range: females 41–53, males 40–50 g/L; normal ferritin range: females 10–150, males 29–248 µg/L.</p