ritonavir and Myocardial-Infarction

We present a case of a 48-year-old white HIV-1 positive man who presented an acute myocardial infarction. The patient was on ART for the last ten years with emtricitabine/tenofovir and ritonavir-boosted fosamprenavir. Eplerenone 25 mg/day was also initiated due to a left ventricular dysfunction. A week after discharge a routine laboratory examination revealed severe hyperkalaemia. Due to suspicion of a potential drug-drug interaction, both eplerenone and ARVs were interrupted. Despite daily treatment for hyperkalaemia, serum potassium levels normalized after two weeks. Eplerenone is metabolized by the hepatic P450 cytochrome isoenzyme CYP3A4; therefore, concomitant administration with CYP3A4 inhibitors, like ritonavir, may increase plasma levels of eplerenone and, therefore, the risk of side effects, mainly hyperkalaemia. Based on this case, it is important to alert the medical community of this possible life-threatening drug-drug interaction between eplerenone and ritonavir-boosted protease inhibitor.

Topics: Drug Interactions; Eplerenone; HIV Infections; HIV Protease Inhibitors; Humans; Hyperkalemia; Male; Middle Aged; Myocardial Infarction; Pharmaceutical Preparations; Ritonavir

Patients with HIV are at an increased risk for cardiovascular disease, both as a result of treatment with protease inhibitors and from the disease itself. The medication regimens of patients with HIV and cardiovascular comorbidities are complex and require careful assessment for potentially serious drug-drug interactions. We report a case of clopidogrel non-responsiveness in a patient with HIV, latent tuberculosis and cardiovascular disease with a history of myocardial infarction. To our knowledge, this is the first report of significant drug interactions between clopidogrel, isoniazid and ritonavir. This case underscores the importance of a detailed drug interaction screening in infectious disease patients taking complex medication regimens, including clopidogrel.

Topics: Antitubercular Agents; Clopidogrel; Drug Interactions; Drug Resistance; HIV Infections; HIV Protease Inhibitors; Humans; Isoniazid; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Ritonavir; Ticlopidine; Tuberculosis

To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study.. Prospective cohort collaboration.. Poisson regression was used to investigate the association between cumulative exposure to ATV and MI/stroke risk after adjusting for known demographic and clinical confounders, as well as cumulative and recent exposure to specific antiretroviral drugs. Follow-up started on enrolment in the study and ended at the earliest of: a new MI/stroke event, death, 6 months after last clinic visit, or 1 February 2011.. The incidence of MI varied from 0.28 [95% confidence interval (CI) 0.26-0.30)]/100 person-years of follow-up (PYFU) in those with no exposure to ATV to 0.20 (0.12-0.32)/100 PYFU in those with more than 3 years exposure. There was no evidence of an association between cumulative exposure to ATV and MI risk, either in univariate [relative rate/year 0.96 (95% CI 0.88-1.04)] or multivariable [0.95 (0.87-1.05)] analyses. The incidence of stroke was 0.17 (0.16-0.19)/100 PYFU in those with no exposure to ATV and 0.17 (0.10-0.27)/100 PYFU in those with more than 3 years exposure. As with the MI endpoint, there was no evidence of an association with ATV exposure in either univariate [1.02 (0.98-1.05)] or multivariable [0.95 (0.87-1.05)] analyses.. These results argue against a class-wide association between exposure to HIV protease inhibitors and the risk of cardio/cerebrovascular events.

Topics: Adult; Aged; Atazanavir Sulfate; Australia; Comorbidity; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Oligopeptides; Prospective Studies; Pyridines; Risk Factors; Ritonavir; Stroke; Time Factors; Treatment Outcome; United States; Viral Load

There is growing interest in studying age-related diseases, such as coronary artery disease (CAD) and resulting myocardial infarction (MI) in HIV-infected patients. While some cohort studies indicate that several antiretrovirals (ARVs), including the protease inhibitor lopinavir/ ritonavir (LPV/r), are associated with an increased relative risk (RR) of MI, other studies show a reduction of MI and CAD in subjects taking ARVs when compared with HIV+ patients not taking ARV therapy. This manuscript reviews data from Abbott-sponsored clinical trials and pharmacovigilance reporting system.. A systematic search was performed to retrieve cases of MI and CAD in Abbott’s clinical trial and pharmacovigilance safety databases. The rates of MI and CAD, and risk factors for the events were reviewed in detail.. The rate of MI and CAD per 1,000 patient treatment years (PTY) was 1.24 (95% CI = 0.40 - 2.90) and 2.74 (95% CI = 1.37 - 4.90), respectively, for subjects taking LPV/r during clinical trials. The frequency of pharmacovigilance reports of MI and CAD were 2.9 per 100,000 PTY and 3.6 per 100,000 PTY, respectively. Most subjects who had MI and CAD events had multiple baseline risk factors.. Relatively few subjects experienced MI or CAD during Abbott-sponsored clinical trials of LPV/r. Analysis of clinical trial and pharmacovigilance data did not indicate an increased risk of MI or CAD associated with LPV/r compared with the general population. In general, the subjects that experienced MI or CAD had known traditional risk factors suggesting that addressing modifiable risk factors could decrease the risk of MI or CAD. ARVs have not been thoroughly studied in subjects at high risk for MI and CAD, and further studies of this population could identify whether starting ARVs affects the incidences of cardic events in subjects with many traditional risk factors

Topics: Adult; Anti-HIV Agents; Clinical Trials as Topic; Coronary Artery Disease; Female; HIV Infections; Humans; Lopinavir; Male; Myocardial Infarction; Pharmacovigilance; Risk Factors; Ritonavir

The role of exposure to specific antiretroviral drugs on risk of myocardial infarction in human immunodeficiency virus (HIV)-infected patients is debated in the literature.. To assess whether we confirmed the association between exposure to abacavir and risk of myocardial infarction (MI) and to estimate the impact of exposure to other nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and non-NRTIs on risk of MI, we conducted a case-control study nested within the French Hospital Database on HIV. Cases (n = 289) were patients who, between January 2000 and December 2006, had a prospectively recorded first definite or probable MI. Up to 5 controls (n = 884), matched for age, sex, and clinical center, were selected at random with replacement among patients with no history of MI already enrolled in the database when MI was diagnosed in the corresponding case. Conditional logistic regression models were used to adjust for potential confounders.. Short-term/recent exposure to abacavir was associated with an increased risk of MI in the overall sample (odds ratios [ORs], 2.01; 95% confidence interval [CI], 1.11-3.64) but not in the subset of matched cases and controls (81%) who did not use cocaine or intravenous drugs (1.27; 0.64-2.49). Cumulative exposure to all PIs except saquinavir was associated with an increased risk of MI significant for amprenavir/fosamprenavir with or without ritonavir (OR, 1.53; 95% CI, 1.21-1.94 per year) and lopinavir with ritonavir (1.33; 1.09-1.61 per year). Exposure to all non-NRTIs was not associated with risk of MI.. The risk of MI was increased by cumulative exposure to all the studied PIs except saquinavir and particularly to amprenavir/fosamprenavir with or without ritonavir and lopinavir with ritonavir, whereas the association with abacavir cannot be considered causal.

Topics: Adult; Anti-HIV Agents; Carbamates; Case-Control Studies; Cohort Studies; Confidence Intervals; Dideoxynucleosides; Female; France; Furans; HIV Infections; Hospitals, Isolation; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Organophosphates; Regression Analysis; Risk; Ritonavir; Sulfonamides

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.. We report a series of 8 seropositive patients in whom an acute coronary event had occurred between February 1997 and February 1999.. 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.. 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...).. 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.

Topics: Adult; Angina Pectoris; Angina, Unstable; Cholesterol; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Middle Aged; Myocardial Infarction; Risk Factors; Ritonavir; Saquinavir; Smoking; Time Factors; Triglycerides

We report the case of a 40-year-old HIV-positive man, undergoing three-drug antiretroviral therapy for 2 years that included a protease inhibitor (ritonavir). The patient was admitted to our Coronary Care Unit with an acute anterior myocardial infarction. He smoked 20 cigarettes/day and had a family history of hypertension. At the time of hospitalization, triglyceride levels were found to be high (290 mg/dl). Metabolic alterations associated with the prolonged use of protease inhibitors, such as insulin resistance, dyslipidemia and lipodystrophy, have recently been described. This side effect may lead to premature coronary artery disease. Therefore it is mandatory to be aware that treatment with protease inhibitors in HIV-positive patients, despite survival prolongation and lowering of AIDS complications, may accelerate atherosclerosis and precipitate acute coronary events, especially in patients with pre-existing cardiovascular risk factors.

Topics: Adult; Anti-HIV Agents; Didanosine; Drug Therapy, Combination; HIV Infections; Humans; Hypertriglyceridemia; Male; Myocardial Infarction; Reverse Transcriptase Inhibitors; Ritonavir; Stavudine

Topics: Adult; Anti-HIV Agents; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Hypertriglyceridemia; Male; Myocardial Infarction; Risk Factors; Ritonavir