Individuals receiving ritonavir and ritonavir-boosted protease inhibitors are significantly more likely to have elevated cholesterol and triglyceride levels than individuals receiving treatment with indinavir, according to data from a large international cohort study set up to monitor the risk of heart disease in people taking anti-HIV therapy.
The findings were presented earlier this week at the Sixth International Congress on Drug Therapy in HIV Infection, which took place in Glasgow.
The study was set up following reports that patients receiving protease inhibitors who experienced cholesterol elevations were succumbing to heart attacks, even when they had few other risk factors for heart disease.
The DAD study has collected baseline cardiovascular risk data on 17,582 HIV patients in Europe, North America and Australia. Of these patients, 7,729 were receiving PI treatment at baseline.
2,574 patients were receiving nelfinavir, 2,354 indinavir, 576 saquinavir, 515 ritonavir, 1,464 a boosted PI regimen including ritonavir, 72 amprenavir and 174 a dual PI regimen excluding ritonavir.
The researchers calculated the risk of total cholesterol elevations, decreased HDL cholesterol, elevated total cholesterol: HDl cholesterol ratio and elevated triglyceride levels for each drug. This analysis was not able to discriminate between drugs according to duration of prior exposure. However, future analyses of this prospective cohort will be able to show whether these risks change over time, and to what extent cardiovascular event rates can be accurately predicted from lipid profiles in HIV patients.
Lipid increases associated with nelfinavir appeared to be somewhat offset by a reduced risk of an HDL cholesterol level equal to or below 0.9mmol/L.
Dual PI regimens that did not contain ritonavir were not associated with an increased risk of lipid elevations.
A separate presentation, from the University of Alberta, Canada, showed that in HIV-negative adults, a 100mg booster dose of ritonavir administered itwice daily for 14 days resulted in significant increases in total cholesterol, triglycerides and LDKL cholesterol, and a reduction in HDL cholesterol. Addition of lopinavir led to an increase in total cholesterol levels, alhtough triglyceride and LDL cholesterol levels remained unchanged. The increase in total cholesterol was due to an improvement in HDL cholesterol levels.
References
Pradier C et al. Lipid profiles on therapy with PI. The DAD (data collection on adverse events of anti-HIV drugs) study. Sixth International Congress on Drug Therapy in HIV Infection, Glasgow, abstract PL12.1, 2002.
Shafran S et al. The effect of ritonavir (RTV) 100mg bid on serum lipid profiles. Sixth International Congress on Drug Therapy in HIV Infection, Glasgow, abstract P129, 2002.
Note: all values are greater than or equal to, except HDL cholesterol, which is less than or equal to.
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style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'> |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Total cholesterol style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>>6.2mmol/l |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>HDL style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Cholesterol style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>>0.9mmol/l |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>TC/HDL ratio style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>>6.5 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Trigly-cerides style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>>2.3mmol/l |
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style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'> |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>OR |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>P |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>OR |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>p |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>OR |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>p |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>OR |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>P |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Indinavir |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>23 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>__ |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>32% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>__ |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>23% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>__ |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>34% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>__ |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Nelfinavir |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>25% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.28 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.009 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>20% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.61 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.0001 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>16% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.80 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.07 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>33% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.05 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.56 |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Ritonavir |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>37% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.98 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.0001 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>30% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.98 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.92 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>30% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.48 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.04 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>62% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>3.22 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.0001 |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Saquinavir |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>16% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.75 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.10 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>30% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.85 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.47 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>14% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.51 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.02 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>28% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.90 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.47 |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>2 PI inc RTV |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>37% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>2.13 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.0001 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>30% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.79 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.09 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>31% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.42 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.02 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>57% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.95 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.0001 |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>2PI excl RTV |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>25% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.21 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.44 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>29% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.75 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.37 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>22% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.83 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.60 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>47% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.18 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.43 |
|
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>Amprenavir |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>24% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.26 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.53 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>42% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.96 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.92 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>26% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.87 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.78 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>52% |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>1.36 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>0.32 |
style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Arial'>