The effects of lipid-based nutrient supplements containing vitamins and minerals on renal excretion of electrolyte and tenofovir concentrations in blood among Zambian HIV/AIDS patients

Abstract

The Effect of Lipid-Based Nutrient Supplements Containing Vitamins and Minerals on Renal Excretion of Electrolytes and Tenofovir Concentrations in Blood among Zambian HIV/AIDS Patients by Derick Munkombwe Background: Advanced HIV-infection combined with under-nutrition and anti-retroviral therapy (ART) places patients at high risk of electrolyte abnormalities and/or losses as well as increased mortality. Aims: This study evaluated if nutritional supplements would help curtail renal electrolyte loss and determined tenofovir blood concentrations in HIV/AIDS patients. Methods: 130 malnourished HIV-positive patients were enrolled in a sub-study embedded in the „Nutritional Support for African Adults Starting ART (NUSTRAT) trial. Inclusion criteria were, ART-naive, body mass index (BMI) <18.5 kg/m2 and CD4 count <350 cells/μL. Patients received lipid-based nutrient supplements alone (LNS, n=63) or together with vitamins and minerals (LNS-VM, n=67). Blood and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations using spectrophotometric methods. Tenofovir in serum and dried blood spot (DBS) was assayed by chromatographic methods. Results: Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline (p=0.69) between the two groups although the values were above normal physiological ranges (i.e. >6.4%); FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%); p < 0.001) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART. Patient blood tenofovir trough concentrations ranged from 67.0 to 421.1 ng/mL (means±SEM: males, 213±12.7, n=53; females, 223.5±14.2, n=35). Multivariable linear regression of tenofovir concentrations with age, sex, BMI, and CD4 cell count revealed BMI as an independent predictor of blood tenofovir (coefficient -34.3; 95% CI -41.4, -27.1; p<0.001). Stratification of BMI into <18.5 kg/m2 (n=47) or >18.5 kg/m2 (n=41) categories at 12 weeks of ART showed that patients with lower BMI had significantly elevated blood tenofovir concentrations than those with higher BMI (253.7±95.7 ng/mL; 95% CI 224.1-282.3 versus 166.2±85.9 ng/mL; 95% CI 136.7-195.7, p<0.001). Conclusions: The LNS-VM regimen appeared to offer protection against phosphate and potassium loss. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients. Malnourished HIV/AIDS patients attained a relatively higher blood tenofovir concentration that was inversely correlated with their BMI. High drug concentrations may predispose patients to drug-related adverse events.