Indinavir did not further increase mean triglyceride levels in HIV-infected patients treated with nucleoside reverse transcriptase inhibitors: an analysis of three randomized clinical trials.
OBJECTIVE
Metabolic abnormalities including hyperlipidemia have developed in patients infected with the human immunodeficiency virus (HIV) after treatment with protease inhibitor drugs. It is unclear whether the deleterious effects on plasma triglyceride concentrations observed in patients receiving highly active antiretroviral therapy are a class effect of protease inhibitors. Hypertriglyceridemia may constitute a risk factor for cardiovascular disease. The purpose of this retrospective analysis of HIV-infected patients enrolled in three randomized, double-blind trials of indinavir therapy was to determine whether indinavir use was associated with a larger increase in triglyceride levels than treatment without a protease inhibitor.


METHODS
Using a mixed-effects model, we compared average changes in nonfasting plasma triglyceride levels among randomized treatment groups for each protocol separately.


RESULTS
The median increase in triglyceride levels during the 1st year of antiretroviral monotherapy was less with indinavir than with either zidovudine or stavudine. The combination of indinavir and nucleoside-analogue reverse-transcriptase inhibitors (NRTI) resulted in smaller increments in triglyceride levels than NRTI monotherapy. Indinavir also augmented the reduction in triglyceride levels observed with combination therapy using zidovudine and lamivudine in persons with far advanced HIV-infection. However, up to 7% of patients receiving a NRTI and indinavir experienced elevations of nonfasting triglyceride levels in excess of 750 mg/dl.


CONCLUSIONS
On average, the combination of indinavir and NRTI therapy was not associated with a greater elevation of non-fasting triglyceride levels in HIV-infected men with at least moderately advanced immunosuppression than treatment with NRTI drugs alone.
Rojas
Carlos
C
University of North Carolina, Chapel Hill, North Carolina, USA.
Coplan
Paul M
PM
Rhodes
Thomas
T
Robertson
Michael N
MN
DiNubile
Mark J
MJ
Guess
Harry A
HA
D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects*; D019469:Indinavir / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000009:adverse effects* / Q000097:blood*; D015215:Zidovudine / Q000627:therapeutic use*
D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides; D015215:Zidovudine; D019469:Indinavir