The Effect of β-Carotene Supplementation on the Pharmacokinetics of Nelfinavir and Its Active Metabolite M8 in HIV-1-infected Patients

Abstract

β-Carotene supplements are often taken by individuals living with HIV-1. Contradictory results from in vitro studies suggest that β-carotene may inhibit or induce cytochrome P450 enzymes and transporters. The study objective was to investigate the effect of β-carotene on the steady-state pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1 infected individuals. Twelve hour nelfinavir pharmacokinetic analysis was conducted at baseline and after 28 days of β-carotene supplementation (25,000 IU twice daily). Nelfinavir and M8 concentrations were measured with validated assays. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Geometric mean ratios comparing day 28 to day 1 area under the plasma concentration-time curve (AUC0–12 h), maximum (Cmax) and minimum (Cmin) concentrations of nelfinavir and M8 are presented with 90% confidence intervals. Eleven subjects completed the study and were included in the analysis. There were no significant differences in nelfinavir AUC0–12 h and Cmin (−10%, +4%) after β-carotene supplementation. The M8 Cmin was increased by 31% while the M8 AUC0–12 h and Cmax were unchanged. During the 28 day period, mean CD4+ % and CD4+:CD8+ ratio increased significantly (p < 0.01). β-carotene supplementation increased serum carotene levels but did not cause any clinically significant difference in the nelfinavir and M8 exposure.

Micronutrient Deficiency and Treatment Adherence in a Randomized Controlled Trial of Micronutrient Supplementation in ART-Naïve Persons with HIV

“…The role of micronutrient supplementation in stabilizing or delaying immune decline in persons not on ART can only be evaluated within a controlled clinical trial. A pharmaceutical grade formulation of the high-dose micronutrients was chosen for the experimental intervention in this clinical trial because of its bioavailability and stability, which has been problematic in other settings [16,29]. While demanding of participants, the 16-capsule daily regimen allows for a more definitive trial given pharmaceutical stability and adherence.…”

Vitamin A and Beta-Carotene Concentrations in Adults with HIV/AIDS on Highly Active Antiretroviral Therapy

“…Several properties of this micronutrient supported the hypothesis that it could influence HIV disease, including its importance in maintaining normal immune responses, its ability to act as an antioxidant, and its role as a provitamin A molecule. There are few clinical trials investigating the effect of beta-carotene supplementation (11,12) in HIV/AIDS patients. The studies do not show a benefit, but they involved a relatively small sample size.…”

Pharmacokinetic Outcomes of the Interactions of Antiretroviral Agents with Food and Supplements: A Systematic Review and Meta-Analysis

“…While nine studies investigated the effects of food or nutrient supplement on ARV pharmacokinetics [ 12 , 14 , 25 , 27 , 32 , 38 , 42 , 43 , 44 ]. The rest of the studies explored the pharmacokinetic interactions between ARV and vitamins or minerals [ 15 , 29 , 34 , 36 , 37 , 40 ], and dietary supplements [ 28 , 31 , 33 , 35 , 39 , 41 ]. Most studies showed non-significant changes in ARV pharmacokinetic parameters when co-administered with meals.…”