Serum Phosphate Predicts Early Mortality in Adults Starting Antiretroviral Therapy in Lusaka, Zambia: A Prospective Cohort Study

Abstract

BackgroundPatients starting antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression.Methodology/Principal FindingsAn observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI) <16 kg/m2 or CD4+ lymphocyte count <50 cells/µL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP) were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43), compared to 1.06 mmol/L (IQR: 0.89, 1.27) among those who died (p<0.01). Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95). The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience.Conclusions/SignificanceLow serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.

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

“…We previously reported that the absolute value of one-week serum phosphate and the change from the pre-treatment level were not significantly associated with mortality in this cohort, as might be observed in the refeeding syndrome [13]. This condition is classically defined by electrolyte and fluid shifts over a period of several weeks in response to increased carbohydrate intake among nutritionally depleted individuals, which predisposes to a range of cardiovascular, respiratory and neurologic sequelae, and death [14,15,29].…”

“…The study setting, eligibility criteria, design and procedures have been previously described [13]. Briefly, individuals were eligible for enrolment if they: qualified for ART according to Zambian national guidelines in place at the time (i.e., WHO stage 4 disease, a CD4 + lymphocyte count below 200 cells/mm 3 , or WHO stage 3 disease and a CD4 + lymphocyte count below 350 cells/mm 3 ); were intending to start therapy the same day; met the BMI and/or CD4 + threshold criteria; and agreed to adhere to the study visit schedule and laboratory testing requirements.…”

“…Phosphate and albumin were measured at each subsequent study visit, while ferritin measurements were repeated at one, two, four and 12 weeks, and highly sensitive C-reactive protein (hsCRP) measurements were repeated at one, four and 12 weeks post-ART initiation. Thirteen participants received phosphate supplementation according to predetermined algorithm based on serum level [13]. …”

Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa

“…The first principal component was extracted for age, BMI, square root of CD4+ lymphocyte count, hemoglobin, and phosphate using the ‘princomp()’ function from the covariance matrix in R software. We adjusted for serum phosphate due to our prior finding that hypophosphatemia is an independent predictor of early mortality in this population (23) . If a participant had no recorded appetite or intake values within a given time interval, he or she was dropped from the risk set for that interval.…”

Glycerophosphocholine Utilization by Candida albicans

“…GroPCho Utilization under Serum Growth Conditions-To explore GroPCho transport under conditions more similar to those experienced in a human host, we performed GroPCho incorporation experiments in the presence of 10% serum and 1 mM KH 2 PO 4 , which is within the phosphate concentration range reported for serum (42). Cultures were grown for 6 h at 37°C in the presence of [ 3 H]GroPCho, and the internal metabolites were analyzed (Fig.…”