Low blood phosphorus levels are associated with high death rates in the initial weeks of antiretroviral therapy (ART) in AIDS patients in sub-Saharan Africa, according to new research conducted by University of Alabama at Birmingham (UAB) researchers at the UAB-affiliated Centre for Infectious Disease Research in Zambia (CIRDZ).
In findings published May 18 in PLoS ONE, the researchers say low phosphorus seems to be a strong predictor of early death among patients beginning ART therapy.
Studies done at CIRDZ and elsewhere had previously shown high mortality in AIDS patients within the first 30 days of starting ART. In 2006, Douglas Heimburger, M.D., at the time a professor of nutrition sciences at UAB and now the associate director for education and training at the Vanderbilt Institute for Global Health, began an observational study at CIDRZ in Lusaka, Zambia, after speculating that the cause might be linked to severe weight loss, a feature common in advanced AIDS.
"There is a precedent with a condition known as refeeding syndrome, seen in prisoners of war following World War II," said Heimburger. "A significant number of prisoners who were underweight and malnourished upon release from captivity died within the first few weeks after access to unlimited amounts of food."
Heimburger says studies done after the war showed that when the former prisoners ate their fill, their cells went on an uncontrolled phosphorus binge, consuming all the available phosphorus in the blood, leading to heart and lung failure.
The research team enrolled 142 patients initiating ART at the Chawama primary care clinic in Lusaka in 2006-07. Twenty five participants died during the 12-week follow up period, with 10 dying within the first four weeks. Baseline phosphorus levels were significantly higher among participants still alive at 12 weeks compared to those who had died. Thirteen patients received phosphorus supplementation due to exceedingly low levels at some time during the study.
"The scope and design of this trial do not let us conclusively claim that low phosphorus causes early mortality in these patients, but low blood phosphorus at the time of initiating ART does serve as a strong predictor of death among patients with advanced HIV disease," said Edmond Kabagambe, DVM, Ph.D., assistant professor of epidemiology in the UAB School of Public Health and a study co-author. "The relation between low phosphorus and early mortality may represent a physiologic phenomenon similar to the refeeding syndrome. Additional research is warranted to establish a conclusive relationship and to examine potential therapeutic interventions."
Heimburger says additional studies in Zambia are envisioned to better understand the link between phosphorus and death among this patient group and possibly to implement phosphorus supplementation programs for those with low phosphorus levels at the start of ART.
"Low phosphorus may be one of several factors that are involved in the observed high mortality rate," said Heimburger. "The tragedy here is that ART is very successful in moderating AIDS symptoms and prolonging lifespan, assuming patients can survive the first few months on therapy."
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