Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy.
OBJECTIVE
Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models.


METHODS
We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral.


RESULTS
One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment).


CONCLUSIONS
These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.
Young
Jim
J
Basel Institute for Clinical Epidemiology, University Hospital Basel, Switzerland. jyoung@uhbs.ch
Glass
Tracy R
TR
Bernasconi
Enos
E
Rickenbach
Martin
M
Furrer
Hansjakob
H
Hirschel
Bernard
B
Tarr
Philip E
PE
Vernazza
Pietro
P
Battegay
Manuel
M
Bucher
Heiner C
HC
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D000069446:Atazanavir Sulfate; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced*; D015233:Models, Statistical; D009842:Oligopeptides / Q000009:adverse effects; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D018119:Stavudine / Q000009:adverse effects; D013557:Switzerland
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D018119:Stavudine