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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
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[Acute coronary syndromes in patients treated with HIV protease inhibitors]
O Barthélémy1, L Escaut, F Vayre
1Service de Cardiologie, Hôpital Cochin, 27 rue du Fg Saint-Jacques, F75679 Paris. olivier.barthelemy@nck.ap-hop-paris.fr
Insights
Highly active antiretroviral therapy (HAART) has reduced opportunistic infections in HIV patients. However, protease inhibitors in HAART may increase cardiovascular risk, leading to accelerated atherosclerosis and acute coronary events.
Area of Science:
- Cardiology
- Infectious Diseases
- Pharmacology
Background:
- Highly active antiretroviral therapy (HAART) has transformed HIV management since 1996.
- While reducing opportunistic infections, concerns arose regarding cardiovascular complications associated with protease inhibitors.
Purpose of the Study:
- To investigate the potential link between HIV protease inhibitor treatment and acute coronary events.
- To analyze the characteristics and outcomes of HIV-positive patients experiencing cardiac events while on HAART.
Main Methods:
- Case series of 8 human immunodeficiency virus (HIV)-positive patients experiencing acute coronary events between February 1997 and February 1999.
- Review of patient history, cardiovascular risk factors, and antiretroviral regimens, including protease inhibitors.
Main Results:
- All patients were young, HIV-positive, and on protease inhibitor therapy, with cardiovascular risk factors like smoking and dyslipidemia.
- Six patients had myocardial infarction, one unstable angina, and one effort angina.
- Metabolic changes including elevated triglycerides (especially with ritonavir), cholesterol, and LDL-cholesterol were observed; glucose intolerance noted with indinavir.
Conclusions:
- Acute coronary events in these patients appeared linked to protease inhibitor treatment, potentially causing metabolic disorders and endothelial dysfunction.
- Coronary lesions were typically single-artery and proximal/median.
- Nelfinavir might have a lower cardiovascular risk profile compared to other protease inhibitors.
- Prognosis was fair with therapeutic adjustments, emphasizing the need for rigorous monitoring and further research.
Introduction:
Cardiovascular complications occurring in patients infected by the human immunodeficient virus (HIV) have considerably changed since the appearance, in April 1996, of highly active antiretroviral tri-therapy (HAART), associating reverse transcriptase and protease HIV-1 inhibitors. The spectacular efficacy of anti-proteases has led to the almost complete disappearance of these opportunistic complications. However, in May 1998, acute coronary accidents were reported in the literature, thus questioning the possible responsibility of antiprotease treatment in the occurrence of accelerated atheroma.
Method:
We report a series of 8 seropositive patients in whom an acute coronary event had occurred between February 1997 and February 1999.
Results:
The patients were young and all exhibited cardiovascular risk factors (smoking, dyslipidemia) and were treated with HIV-1 protease inhibitors. Six patients presented myocardial infarction, one patient unstable angina and one patient effort angina.
Comments:
A rise in triglycerides was observed principally on ingestion of ritonavir and a rise in cholesterol and LDL-cholesterol with all the antiprotease agents. Glucose intolerance was observed with indinavir. The occurrence of acute coronary events appeared to be related to antiprotease treatment (at the origin of metabolic disorders, endothelial dysfunction...), although it was impossible to say whether the antiprotease agents were responsible for the early atheroma or whether they simply contributed to the event. The coronary lesions were characterized by their number (single artery) and their topography (proximal or median). Nelfinavir may carry less cardiovascular risks than the other antiproteases. Mean term prognosis was relatively good, after therapeutic adjustment (change in antiprotease, strategic measures against cardiovascular risk factors, introduction of anti-anginal treatment...).
Conclusion:
Larger and longer studies would help to specify the role of antiproteases in the occurrence of early coronary events. Rigorous monitoring (lipid and glucose measurements, tests to search for myocardial infarction,..) together with the development of new antiretroviral molecules would reduce the number of coronary events in this type of patient.
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