Relationships between drug exposure, changes in metabolic parameters and body fat in HIV-infected patients switched to a nucleoside sparing regimen.
BACKGROUND
The pathogenesis of metabolic disturbances in treated HIV infection is incompletely understood.


METHODS
Relationships between fasted metabolic parameters, body composition, and drug plasma concentrations were investigated in 59 patients who switched from failed nucleoside analogue treatment to ritonavir-boosted indinavir and efavirenz therapy. Metabolic parameters, peripheral fat, visceral adipose tissue (VAT) and drug plasma concentrations were measured prospectively.


RESULTS
Ritonavir exposure was found to be negatively correlated with high-density lipoprotein cholesterol (HDL-c) changes, with a 2.4% decrease in HDL-c for each unit increase in ritonavir concentration ratio. Significant associations between indinavir or efavirenz concentrations and metabolic disturbances were not observed. Total cholesterol (TC) correlated positively with high body mass index (BMI) and negatively with baseline limb fat mass: each unit increase in BMI and each kilogram reduction in baseline limb fat corresponded with a TC increase of 2.4% and 4.1%, respectively. Baseline triglyceride levels were lower in those patients with relatively greater limb fat mass: each kilogram reduction of total limb fat mass was associated with a 15.7% increase in triglyceride concentration. Changes in VAT were positively correlated with TC: for every unit TC increase a 0.3% VAT increase was observed (over 48 weeks).


CONCLUSIONS
Reduced limb fat mass at the start of the study treatment, increases in VAT mass, and higher plasma concentrations of ritonavir on study treatment were each--to varying degrees--associated with various metabolic disturbances.
Autar
Reshma S
RS
The HIV-Netherlands Australia Thailand Research Collaboration - Thai Red Cross AIDS Research Center, Bangkok, Thailand.
Boyd
Mark A
MA
Wit
Ferdinand W M N
FW
Ruxrungthams
Kiat
K
Sankote
Jongkol
J
Lange
Joep
J
Cooper
David A
DA
Phanuphak
Praphan
P
Burger
David M
DM
Reiss
Peter
P
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001823:Body Composition; D050218:Body Fat Distribution; D015992:Body Mass Index; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D003521:Cyclopropanes; D005121:Extremities; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D013785:Thailand; D014280:Triglycerides / Q000097:blood
D000480:Alkynes; D048588:Benzoxazines; D008076:Cholesterol, HDL; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides; D019469:Indinavir; D002784:Cholesterol; C098320:efavirenz; D019438:Ritonavir