ritonavir and Coronary-Disease

Ritonavir-boosted protease inhibitor (PI) regimens have provided substantial benefits in the treatment of HIV/AIDS, resulting in improved clinical outcomes. However, treatment toxicities often affect adherence and may influence outcomes. Dyslipidemia is highly prevalent in many patients who receive a boosted PI regimen. The mechanism underlying dyslipidemia is probably multifactorial and may differ among the individual PIs. The prevalence of cardiovascular disease and events appears to be higher in patients treated with boosted PIs, and as long-term survival increases in HIV-infected persons, the long-term effect of dyslipidemia becomes a growing concern. The practitioner must consider the possibility of these adverse effects when choosing the antiretroviral regimen that best suits each patient. Until future studies define the optimal approach, an evaluation of cardiovascular risk factors and treatment of those risk factors according to evidence-based guidelines are warranted.

Topics: Coronary Disease; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Ritonavir

Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of <6% or ≥6%, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were assessed at baseline, week 84, and week 144. Biomarkers were stratified by FRS category. When ritonavir-boosted/nonboosted treatment groups were combined, median hsCRP did not change significantly between baseline (1.6 mg/liter) and week 144 (1.4 mg/liter) in subjects with FRS <6% (p=0.535) or with FRS ≥6% (1.9 mg/liter vs. 2.0 mg/liter, respectively; p=0.102). Median IL-6 was similar for subjects with FRS <6% (p=0.267) at baseline (1.6 pg/ml) and week 144 (1.4 pg/ml) and for FRS ≥6% (2.0 pg/ml vs. 2.2 pg/ml, respectively; p=0.099). Median Lp-PLA(2) decreased significantly (p<0.001) between baseline (197 nmol/min/ml) and week 144 (168 nmol/min/ml) in subjects with FRS <6% and with FRS ≥6% (238 nmol/min/ml vs. 175 nmol/min/ml, respectively; p<0.001). In conclusion, in antiretroviral-naive subjects treated with abacavir-based therapy for 144 weeks, median inflammatory biomarker levels for hsCRP and IL-6 generally remained stable with no significant difference between baseline and week 144 for subjects with either FRS <6% or FRS ≥6%. Lp-PLA(2) median values declined significantly over 144 weeks for subjects in either FRS stratum.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Aged; Anti-HIV Agents; Atazanavir Sulfate; Biomarkers; C-Reactive Protein; Coronary Disease; Dideoxynucleosides; Drug Combinations; Female; HIV Infections; Humans; Inflammation; Interleukin-6; Lamivudine; Lipids; Longitudinal Studies; Male; Middle Aged; Oligopeptides; Pyridines; Risk Assessment; Ritonavir; Treatment Outcome; Young Adult

Topics: Aged; Antiviral Agents; Bradycardia; Comorbidity; Coronary Disease; COVID-19 Drug Treatment; Drug Combinations; Humans; Hypertension; Lopinavir; Male; Ritonavir

The purpose of the study was to conduct a cost-effectiveness analysis and budget impact analysis comparing lopinavir with ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) for antiretroviral-naïve patients with a baseline CD4+ T-cell distribution and total cholesterol (TC) profile as reported in the CASTLE study.. This decision analysis study used a previously published Markov model of HIV disease, incorporating coronary heart disease (CHD) events to compare the short- and long-term budget impacts and CHD consequences expected for the two regimens.. Patients were assumed to have a baseline CHD risk of 4.6% (based on demographic data) and it was also assumed that 50% of the population in the CASTLE study were smokers. The CHD risk differences (based on percent of patients with TC >240 mg/dL) in favor of ATV+RTV resulted in an average improvement in life expectancy of 0.031 quality-adjusted life years (QALYs) (11 days), and an incremental cost-effectiveness ratio of $1,409,734/QALY. Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490. A sensitivity analysis using a cohort of all smokers on antihypertensive medication estimated an average improvement in life expectancy of 31 quality-adjusted days in favor of ATV+RTV, and a cost-effectiveness ratio of $520,861/QALY: a ratio that is still above the acceptable limit within the US.. The use of an LPV/r-based regimen in antiretroviral-naïve patients with a baseline CHD risk similar to patients in the CASTLE study appears to be a more cost-effective use of resources compared with an ATV+RTV-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings expected with the use of LPV/r in antiretroviral-naïve individuals with average to moderately elevated CHD risk.

Topics: Anti-HIV Agents; Atazanavir Sulfate; Budgets; CD4 Lymphocyte Count; Coronary Disease; Cost Savings; Cost-Benefit Analysis; Decision Support Techniques; Drug Costs; Drug Therapy, Combination; HIV Infections; Humans; Life Expectancy; Lopinavir; Markov Chains; Models, Econometric; Oligopeptides; Pyridines; Pyrimidinones; Quality-Adjusted Life Years; Ritonavir; Smoking; United States

The choice of initial highly active antiretroviral therapy (HAART) should take into account the need to balance efficacy, adverse event risk, resistance concerns for the treatment of HIV and treatment costs. Increased risk of coronary heart disease (CHD) may be of special concern in the selection of HAART therapy, because differences in potential CHD risk have been reported for different regimens. This study aimed to estimate the long-term combined effects of HIV disease and antiretroviral (ARV)-related risk for CHD on quality-adjusted survival and healthcare costs for ARV-naive patients.. A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. In the model, the average patient was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir or unboosted atazanavir as the first protease inhibitor (PI). Clinical trial data were used to estimate the differences between these two therapies. The daily PI costs were $US18.52 for lopinavir/ritonavir and $US22.08 for atazanavir. Other costs were estimated from Medicaid billing databases and average wholesale drug price reports. All model costs were reported as the 2004 present value in US currency. The model's time horizon reflected a patient's lifetime, and the perspective of the analysis was that of the healthcare system and did not include indirect costs in the model cost estimates. Various CHD risk levels were tested in the sensitivity analysis.. In the base case, the model predicted a median duration of initial PI regimen of 5.6 years for lopinavir/ritonavir and 3.8 years for atazanavir. Over 10 years, patients who started on atazanavir had 30 additional AIDS events per 100 patients. Only 0.7 additional CHD events per 100 patients occurred for those who started on lopinavir/ritonavir. The model estimated 10-year total healthcare cost savings of $US12,543 per patient in the lopinavir/ritonavir group. The lifetime incremental cost effectiveness of lopinavir/ritonavir versus atazanavir was $US6797 per quality-adjusted life-year gained.. Lopinavir/ritonavir is a highly cost-effective regimen relative to atazanavir for the treatment of HIV. The effect of lopinavir/ritonavir on long-term CHD risk was minimal compared with the increased risk of AIDS/death projected for a less efficacious first PI regimen. The cost of lipid-lowering drugs and treatment of CHD for patients taking the lopinavir/ritonavir regimen was only 1.2% of the cost of AIDS care per person, which was too small to have a significant effect on the overall cost savings with lopinavir/ritonavir therapy. Thus, a decision to forgo potency and durability in an ARV regimen for an ARV-naive patient in favour of a less potent regimen with an improved lipid profile may prove to be costly over time, in terms of both budget impact and life expectancy.

Topics: Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Coronary Disease; Cost-Benefit Analysis; Fees, Pharmaceutical; Health Care Costs; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Markov Chains; Models, Statistical; Oligopeptides; Pyridines; Pyrimidinones; Quality-Adjusted Life Years; Ritonavir; Survival Analysis; Survival Rate; Time Factors

To estimate the cost effectiveness and long-term combined effects of HIV disease and antiretroviral (ARV) therapy-related risk for coronary heart disease (CHD) on quality-adjusted survival and healthcare costs for ARV-experienced patients.. A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. The representative patient in the model was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). The proportions of patients with viral suppression below 400 and 50 copies/mL, respectively, at week 48 reported in clinical trials were used to estimate the differences between these two therapies. The daily ARV costs were $US 24.60 for LPV/r capsules (2005 costs) and $US 26.54 for LPV/r tablets (2006 costs), $US 29.76 for ATV and $US 8.57 for ritonavir (2005 costs). Costs of other ARV drugs were taken from average wholesale drug reports for 2005. The cost of AIDS events was estimated from Medicaid billing databases and reflected a medical care system perspective and 2005 treatment costs. Cost-effectiveness calculations assumed a lifetime time horizon. The effects of different model assumptions were tested in a multiway sensitivity analysis by combining extreme values of parameters.. The model estimated a clinical and economic advantage to using LPV/r over ATV+RTV, which varied depending upon the use of LPV/r capsules or tablets. Using LPV/r capsules was comparatively beneficial for ARV-experienced patients in quality-adjusted life-months (QALMs) of 4.6 (corrected for differences in CHD risk) compared with ATV+RTV. In addition, there were 5- and 10-year overall per-patient cost savings of $US 17,995 and $US 21,298, respectively. Estimates for the LPV/r tablet formulation approved in 2005 (assuming similar efficacy) improved cost savings over 5- and 10-year periods to $US 19,598 and $US 23,126 per patient, respectively, because of a drug price differential. Sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. Model limitations were the uncertainty associated with the model parameters used.. LPV/r appears to be a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV. The long-term CHD risk associated with LPV/r was minimal compared with the increased risk of AIDS/death and costs projected for a less efficacious PI-based regimen.

Topics: Adult; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Coronary Disease; Costs and Cost Analysis; Data Collection; Drug Combinations; HIV Infections; HIV Protease Inhibitors; Humans; Lopinavir; Male; Markov Chains; Models, Statistical; Pyrimidinones; Quality of Life; Quality-Adjusted Life Years; Ritonavir; Survival Analysis; United States; Viral Load

Selection of antiretroviral therapy (ART) for antiretroviral-experienced patients should involve balancing multiple factors, including clinical efficacy, adverse-event risk, resistance concerns, cost effectiveness and expected budget impact. The efficacy of a regimen and its durability, as demonstrated in controlled clinical trials, must be considered in the light of short- and long-term economic impacts on the healthcare system. These impacts may vary based on drug costs, costs of reported adverse effects, the regimen's likelihood of contributing to viral resistance to second-line therapies and the marginal cost differences between other healthcare resources used over a patient's lifetime. Risk of coronary heart disease (CHD) may be of concern in the selection of ART, because differences in CHD risk factors have been reported for different regimens, and heart disease is both a deadly and costly condition. This study set out to estimate the long-term combined effects of HIV disease and antiretroviral-related risk for CHD on quality-adjusted survival and healthcare costs for antiretroviral-experienced patients in the UK, Spain, Italy and France.. A previously validated Markov model was updated with 2006 cost estimates for each of the four countries and supplemented with the Framingham CHD risk equation. In the model, the average patient was male, aged 37 years, with a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). Clinical trial results, local drug costs and AIDS and CHD cost estimates were used to estimate the differences between these two therapies.. There was a significant advantage using LPV/r over ATV+RTV, which varied depending on the country's cost structure and assumptions related to drug efficacy. There was a comparative benefit for experienced patients in quality-adjusted life-months (QALM) of 4.6 (the net gain after subtracting quality-adjusted life-years [QALYs] lost owing to CHD risk). In addition, there were 5- and 10-year overall cost savings of between euro947 and euro6594 per patient after 5 years, and an impact ranging from a cost increase of euro308 (for France) to a cost saving of euro7388 (for Spain) at year 10. The lifetime incremental cost-effectiveness ratios ranged from dominant for Spain to euro11 856/QALY for Italy.. LPV/r was a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV for each of the four countries examined in this study. The effect of LPV/r on long-term CHD risk was minimal compared with the increased risk of AIDS/death projected for a less efficacious PI-based regimen. The cost of lipid-lowering drugs and treatment for CHD was insignificant compared with the overall cost savings from LPV/r therapy. The choice of regimen for antiretroviral-experienced patients should be based on a regimen's expected efficacy and durability for countries with similar cost structure to those examined here.

Topics: Adult; Atazanavir Sulfate; Coronary Disease; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; France; Health Care Costs; HIV Infections; HIV Protease Inhibitors; Humans; Italy; Lopinavir; Male; Markov Chains; Oligopeptides; Pyridines; Pyrimidinones; Quality-Adjusted Life Years; Risk Factors; Ritonavir; Spain; Time Factors; United Kingdom

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.

Topics: Adult; Anti-HIV Agents; Cholesterol; Coronary Disease; Cross-Sectional Studies; Drug Therapy, Combination; Female; HIV Infections; Humans; Indinavir; Lipids; Logistic Models; Male; Prospective Studies; Ritonavir; Saquinavir; Triglycerides

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Anti-HIV Agents; Carbamates; Coronary Disease; Dideoxynucleosides; Drug Therapy, Combination; Furans; Hepatitis B; HIV Protease Inhibitors; Humans; Hyperlipoproteinemias; Male; Middle Aged; Pancreatitis; Risk Factors; Ritonavir; Sulfonamides

Most cholesterol-lowering drugs belong to a class called statins, which are metabolized by CYP3A liver enzymes. Protease inhibitors are also statins. Using cholesterol-lowering drugs and protease inhibitors at the same time can lead to toxicity problems, because of the raised level of statins in the body. People who take Ritonavir are especially cautioned to avoid cholesterol-lowering statins and instead are advised to try lipid-regulating drugs such as Lopid (Gemfibrozil). Lipitor (atorvastatin) and Pravachol (Pravastatin) are cholesterol-lowering statins that are metabolized less by CYP3A, compared to other statins, and therefore may be possible alternatives.

Topics: Anticholesteremic Agents; Coronary Disease; Cytochrome P-450 Enzyme System; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir