Severe malnutrition is associated with early mortality in HIV-infected African adults starting Antiretroviral Therapy (ART). A trial conducted to test the effect of administration of a high content of vitamins and minerals in a Lipid-based Nutritional Supplement (LNS) on mortality, in malnourished adults referred for ART, showed that changes in serum electrolytes were more strongly associated with mortality than were absolute electrolyte levels.
Malnutrition is a common complication of the Human Immunodeficiency Virus (HIV) infection and it plays an independent role in morbidity and mortality of HIV-infected patients. Severe malnutrition, usually indicated by a low BMI, is associated with disordered metabolism of Sodium (Na), Potassium (K), Phosphate (P), and Magnesium (Mg). Malnourished HIV-infected patients starting antiretroviral therapy are at high risk of early mortality, which may be partly attributed to altered electrolyte metabolism.
The British Journal of Nutrition recently published a study conducted by A. M. Rehman et al. to determine the effects of electrolyte imbalance in malnourished HIV-infected African adults on mortality. They used data from the African Adults Starting Antiretroviral Therapy (NUSTART) trial. Electrolyte-enriched Lipid-based Nutritional Supplement (LNS) were used in this trial to determine the association of baseline and time-varying concentrations of serum phosphate and potassium with mortality within the first 12 weeks of starting Antiretroviral Therapy (ART). NUSTART was an individually randomized, controlled trial that used a two-stage dietary protocol that mimicked nutritional management of malnourished children. The study compared LNS either with (LNS-VM) or without (LNS) high levels of vitamins and minerals among patients who were HIV-positive and malnourished.
Patients were seen weekly from recruitment until the ART start visit, then at 2, 4, 6, 8, and 12 weeks after starting ART. A total of 9096 serum phosphate measurements were taken from 1764 patients and for serum potassium 8773 measures were obtained from 1710 patients (a median of 6 per patient for each).
The results from the trial showed that vitamin and mineral fortification of the LNS did not decrease mortality within the first 12 weeks of ART initiation compared with unfortified LNS. The LNS-VM was also associated with increased incidence of both high phosphate and high potassium and decreased incidence of low phosphate. Previous studies have shown an increase in mortality associated with low serum phosphate levels. However, NUSTART trial results found that the association between baseline electrolytes and survival is nonlinear. Furthermore, before starting ART, high rather than low levels of phosphate carried a greater risk of early mortality. In view of these results, a secondary analysis of NUSTART data was carried out that involved a detailed time-course analysis of the effects of the LNS-VM intervention, and on the changes in electrolyte levels in relation to mortality.
The secondary analysis provided a more complete picture of how serum electrolytes change over time and in relation to factors such as diet, tissue catabolism or anabolism, ART and renal function. There was strong evidence that changes in phosphate and potassium over time differed in each trial arm i.e. LNS-VM and LNS. On average, in the LNS-VM arm, values of electrolytes were found to increase up to the ART initiation and then decreased to baseline levels by the end of follow-ups. On the other hand, average values in the LNS arm changed little over the follow-up period. The LNS-VM group clearly demonstrated the added effect of supplementing vitamins and minerals. High levels of potassium were not observed at baseline and during intervention measurements, but the level of phosphate was found to be about twice the Recommended Nutrient Intake (RNI) and much lower than the tolerable upper level. This suggests that malnourished HIV-infected adults have a much lower capacity to metabolize phosphate compared with healthy individuals.
After adjusting for other factors related to mortality, there was some evidence to suggest that time-varying electrolytes affected mortality. These results indicate that changes in serum electrolyte values, rather than the absolute values, are strongly associated with mortality. The changes appear to have the greatest effects for phosphate, and increased supplementary amounts of electrolytes in LNS-VM may have accentuated this effect in the study.
The biggest strengths of this study are the large longitudinal sample size and time-based comparison of results from referral to ART initiation. Despite its strengths, this study suffers from a few limitations, such as the absence of detailed dietary intakes of participants, and the fact that phosphate levels in the supplements used for the study were measured by the manufacturer, not the researchers.
Although malnourished HIV-infected patients need phosphate and potassium for tissue deposition during recovery, this study recommends that high doses of electrolytes should not be administered to HIV-infected patients to improve nutritional status early after starting ART, as these patients do not have the ability to appropriately handle electrolytes, especially phosphate. Both potassium and phosphate can be provided in adequate amounts only after metabolism is stabilized and health of these patients has improved.
Written By: Preeti Paul, MS Biochemistry