Hypophosphatemia in refeeding syndrome as a cause of early mortality in patients initiating antriretroviral therapy in Zambia
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Despite the numerous benefits seen with the introduction of antiretroviral therapy among people living with HIV/AIDS in low-income countries, there has been a surprisingly high mortality rate, especially in the first 90days of therapy. Causes of this early ART mortality are not well known in Zambia. It is probable that the high prevalence of malnutrition in sub-Saharan Africa, exacerbated in persons with HIV disease, is a major factor in early ART mortality.Refeeding syndrome in particular may be responsible for a portion of the early deaths. This syndrome occurs in persons with severe cachexia from any cause who experience sudden increases in food intake and nutrient absorption that exceeds the body's ability to meet the high phosphorous demands for metabolism of carbohydrate. The resulting hypophosphatemia could lead to adverse outcomes including cardiopulmonary failure and death.This study looked at a group of Zambians, who were HIV positive and just about to initiate antiretroviral therapy (ART) and the expected mortality in this group would be high. The aims of the study were:1.To determine whether refeeding syndrome occurs, and estimate its incidence.2.To determine whether persons who develop refeeding syndrome are at higher risk of early ART mortality or near mortality than persons who do not develop refeeding syndrome.Study participants were recruited from Chawama Clinic in Lusaka, Zambia and included 148 ART naive adult men and women initiating treatment and at high risk for early mortality.After obtaining consent, participants were scheduled for routine initiation of ART with usual 2-, 4-, 8-, and 12-week follow up visits after initiation of therapy. Because initial immunologic and clinical responses, intestinal changes, and refeeding syndrome could all occur in the first 1-2 weeks after ART begins, a 1 week post-ART visit was added for the puipose of this study. If eligible, in addition to routine procedures, including obtaining demographic and socioeconomic factors, history and physical exam, disease stage classification, and adherence evaluation, blood samples for hematology, biochemistry and CD4+cell counts were drawn.Serum phosphorus was used as the primary identifying parameter of refeeding syndrome for which hypophosphataemia is a dominant feature. Routine physical examination with emphasis on clinical features of refeeding syndrome and adherence evaluation were also done during the visits.148 participants were seen of whom 90(61%) females and 58(39%) males. Of these 17(11%) met the criterion for refeeding syndrome. In 7 it occurred at two or more visits despite supplementation. There were 28(19%) participants who had mild hypophosphatemia (serum phosphate 0.65-0.8mmol/l) at least once.The prevalence of hypophosphatemia was highest after 1 week of ART. Phosphate levels decreased significantly in the first 1 week in the whole cohort before recovering in week 2 and thereafter. Male gender was found to be a significant risk factor (OR 4.2, 95%CI 1.3-13).Overall 28 deaths were recorded in 30.1 person years of follow up (median 86days).Of these 4 (15%) had refeeding syndrome and 3 had persistently low phosphate despite oral or IV supplementation. Thirteen subjects who met our criteria refeeding syndrome survived after phosphorus supplementation. Mortality was not significantly associated with refeeding syndrome. However; correlation may have been influenced by phosphate supplementation and multiple other independent causes of mortality. Hypophosphatemia occurs early in ART in some Zambian subjects exhibiting major risk factors for early mortality and may be responsible for a portion of the early deaths.
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