ritonavir and Dyslipidemias

HIV infection is a serious but treatable disease, yet current treatment is limited by development of resistance and high rates of adverse drug reactions. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be reliably measured. Increasing knowledge about genes implicated in pharmacokinetics, mode of action, efficacy, and toxicity of drugs has already provided relevant results for clinical practice, for example: The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction. Persons with the allele CYP2B6*6 present higher efavirenz "area under the curve" and have increased risk of neuropsychological toxicity. Additional gene variants are being discovered that influence the action of antiretroviral drugs. And, moreover, it is expected that larger-scale comprehensive genome approaches will profoundly improve the landscape of knowledge of HIV therapy in the future. The present article shows some recent patents related to the treatment of viral infections.

Topics: Alkynes; Anti-Retroviral Agents; Aryl Hydrocarbon Hydroxylases; Atazanavir Sulfate; Benzoxazines; Central Nervous System Diseases; Cyclopropanes; Cytochrome P-450 CYP2B6; Dideoxynucleosides; Drug Hypersensitivity; Drug Resistance, Viral; Dyslipidemias; Genetic Predisposition to Disease; Genetic Testing; Glucuronosyltransferase; HLA Antigens; Humans; Hyperbilirubinemia; Nevirapine; Oligopeptides; Oxidoreductases, N-Demethylating; Patents as Topic; Patient Selection; Pharmacogenetics; Pyridines; Ritonavir

Darunavir, previously known as TMC-114, is a new protease inhibitor (PI) with a high affinity for the HIV-1 protease and strong ability to inhibit its action, even in mutated forms. Consequently, this drug is considered to have great intrinsic potency and a high genetic barrier. At the time of writing, data on the tolerability and safety of darunavir come mainly from studies of late rescue therapy (POWER, DUET), which have included more than 1,600 patients. Recent data, relating to shorter time periods, are also available from studies in early treatment-experienced patients (TITAN) and in treatment-naïve patients (ARTEMIS), increasing experience to a further 600 patients. Lastly, more than 4,000 patients who have received darunavir through the Expanded Access Program have allowed the drug's generally good safety and tolerability profile to be defined. In the studies performed to date, darunavir has been well tolerated, with a better profile than that of the PIs used in control groups in terms of adverse effects such as diarrhea, gastrointestinal tolerability and lipid alterations. Moreover, to date, no unexpected severe adverse effects have been reported.

Topics: Adult; Chemical and Drug Induced Liver Injury; Clinical Trials, Phase III as Topic; Darunavir; Drug Therapy, Combination; Dyslipidemias; Female; Gastrointestinal Diseases; HIV Infections; HIV Protease Inhibitors; Humans; Incidence; Lopinavir; Male; Multicenter Studies as Topic; Pyrimidinones; Randomized Controlled Trials as Topic; Ritonavir; Salvage Therapy; Sulfonamides

Atazanavir is a new azapeptide protease inhibitor with a remarkable pharmacokinetic profile, which means it can be administered in only two capsules once per day in combination with other antiretrovirals. Its strong antiviral efficacy is also accompanied by an excellent tolerance profile and no significant increase in cholesterol and triglyceride levels. The immunological and virological response obtained with atazanavir or atazanavir/ritonavir, in naive patients as well as in patients with previous virological failure with other protease inhibitors, is excellent. Atazanavir is an attractive drug for therapeutic simplification. Besides maintaining virological suppression, patients who change from other PI to atazanavir experience reductions in total cholesterol, HDL cholesterol and triglycerides. Preliminary data suggest that simplified maintenance treatment with atazanavir/ritonavir in monotherapy, can effectively maintain virological suppression in selected patients.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Dyslipidemias; Female; Gastrointestinal Diseases; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hyperbilirubinemia; Lipids; Male; Middle Aged; Multicenter Studies as Topic; Oligopeptides; Pyridines; Ritonavir; Salvage Therapy; Treatment Outcome

Virological failure of antiretroviral treatment increases the morbidity and mortality associated with AIDS. With currently available drugs it is possible to achieve an HIV - PVL < 50 copies of aRNA/mL in a significant percentage of patients with virological failure, even in those who accumulate a considerable number of resistant mutations in the viral genome. Compliance continues to be the most significant cause of antiretroviral treatment failure. Atazanavir boosted with ritonavir has clear advantages over other protease inhibitors (PI), such as its administration once per day, low number of tablets and a good tolerance which helps in compliance, as well as a lower metabolic toxicity and a resistances profile different to other PIs. Boosted Atazanavir in rescue treatments would be strongly recommended in patients naive to a PI or when there are < 3 mutations in the basic genotype in positions: 10F/I/V, 16E, 33I/F/V, 46I/L, 60E, 84V, 85 V and 90M of the protease gene, particularly when the patient has problems of compliance to antiretroviral treatment or metabolic disorders, such as dyslipaemia, insulin resistance, fasting blood glucose changes, a cardiovascular risk at 10 years of > 10% or cardiovascular disease.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Clinical Trials as Topic; Drug Resistance, Viral; Drug Synergism; Dyslipidemias; HIV Infections; HIV Protease; HIV Protease Inhibitors; HIV-1; Humans; Insulin Resistance; Oligopeptides; Patient Compliance; Point Mutation; Pyridines; Ritonavir; Salvage Therapy; Treatment Outcome; Viral Load

To the best of our knowledge, there is no published study on the use of interferon β-1a (IFN β-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN β-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN β-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-μg/ml (12 million IU/ml) dose of interferon β-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively,

Topics: Adult; Aged; Antiviral Agents; Atazanavir Sulfate; Betacoronavirus; Cardiovascular Diseases; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hydroxychloroquine; Intensive Care Units; Interferon beta-1a; Length of Stay; Lopinavir; Male; Middle Aged; Neoplasms; Pandemics; Patient Safety; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Survival Analysis; Treatment Outcome

Dyslipidemia as a risk factor of cardiovascular disease is common especially in HIV-infected patients who are using protease inhibitors (PIs) including atazanavir. Pitavastatin has less drug-drug interactions and demonstrable efficacy in decreasing lipid levels in non HIV-infected individuals.. This study was a randomized, double-blind, crossover study comparing the safety and efficacy of pitavastatin vs placebo in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir (ATV/r). Patients were randomized to receive either placebo or pitavastatin for 12 weeks. The follow-up visits were every 4 weeks until the end of the study.. A total of 12 HIV-infected patients were enrolled to each study group. Of all, 14 (58%) patients were men and mean (standard deviation, SD) age was 48.1 (1.8) years. At 12 weeks of treatment with pitavastatin compared to placebo; mean [95% confidence interval (CI)] total cholesterol (TC) was 207 (187.3, 226.8) mg/dL vs 246.3 (226.5, 266) mg/dL (p <0.001); mean (95% CI) triglyceride (TG) was 351.3 (193.2, 509.4) mg/dL vs 279.1 (121, 437.2) mg/dL (p = 0.269); mean (95% CI) high density lipoprotein (HDL) was 45.3 (40.4, 50.2) mg/dL vs 44.2 (39.3, 49.1) mg/dL (p = 0.354); and mean (95% CI) low density lipoprotein (LDL) was 113.2 (100.4, 126) mg/dL vs 145.6 (132.8, 158.4) mg/dL (p <0.001). Mean liver enzyme and median creatine phosphokinase levels were not statistically significant between patients receiving placebo and pitavastatin.. Pitavastatin decreases TC and LDL level at 12 weeks significantly and shows indifferent in hepatotoxicity and creatine phosphokinase levels compared to those of placebo. Thus, pitavastatin can be a good option of lipid-lowering agent in HIV-infected patients who are receiving ATV/r.. ClinicalTrials.gov NCT02442700.

Topics: Adult; Atazanavir Sulfate; Cholesterol; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Dyslipidemias; Female; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Lipoproteins, LDL; Male; Middle Aged; Quinolines; Ritonavir; Treatment Outcome; Triglycerides

HIV infection is associated with an atherogenic lipoprotein profile, and ritonavir-boosted protease inhibitors exacerbate this phenotype. We evaluated the effect of 45 days of rosuvastatin versus pravastatin on the low-density lipoprotein (LDL) size and the distribution of LDL subfractions in HIV-1 patients receiving boosted protease inhibitors with elevated LDL levels.. Substudy of the randomized double-blind multicentre ANRS 126 VIHstatine trial.. Twenty clinical centres in France.. HIV-infected patients receiving boosted protease inhibitors with dyslipidaemia (LDL cholesterol > 4.1 mmol/l and triglycerides < 8.8 mmol/l).. Rosuvastatin 10 mg/day (n = 39) or pravastatin 40 mg/day (n = 37) for 45 days.. LDL size and distribution of LDL subfractions blindly assessed by gradient gel electrophoresis at baseline and at day 45.. Rosuvastatin was more effective than pravastatin in increasing the diameter of the LDL peak. The LDL diameter change was 0.33 ± 0.59 nm in the rosuvastatin group versus -0.01 ± 0.52 nm in the pravastatin group (P = 0.021). Rosuvastatin was also more effective in increasing significantly the percentage of large LDL (LDL1, P = 0.038; LDL2, P = 0.031) and in decreasing the percentage of small LDL (LDL3, P = 0.009).. Rosuvastatin was more effective than pravastatin in normalizing LDL size and LDL subfraction distributions, leading to a less atherogenic phenotype.

Topics: Adult; Anticholesteremic Agents; Cholesterol, LDL; Double-Blind Method; Dyslipidemias; Female; Fluorobenzenes; France; HIV Protease Inhibitors; HIV Seropositivity; HIV-1; Humans; Male; Middle Aged; Pravastatin; Pyrimidines; Ritonavir; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome

Dyslipidaemic effects of antiretrovirals (ARVs) may contribute to increased cardiovascular risk (CR) in HIV-1-infected patients. The ARTEN (atazanavir/ritonavir on a background of tenofovir and emtricitabine vs. nevirapine on the same background, in naïve HIV-1-infected patients) study compared prospectively ritonavir-boosted atazanavir (ATZ/r) 300 mg/100 mg once daily (qd) with immediate release nevirapine (NVP) 200 mg twice daily or 400 mg qd, each combined with fixed-dose tenofovir 300 mg/emtricitabine 200 mg qd in 569 ARV-naïve HIV-1-infected patients. Lipid profiles and CR from baseline to week 48 are reported.. Changes from baseline to week 48 in fasting plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), TC:HDL-c ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total triglycerides (TG) were determined. The Framingham algorithm was used to estimate CR. Analysis was by intention-to-treat (ITT) with last observation carried forward (LOCF) for missing data.. At week 48, NVP treatment resulted in significantly greater mean increases from baseline in TC (24.4 vs. 19.6 mg/dL; P=0.038), HDL-c (9.7 vs. 3.9 mg/dL; P<0.0001), LDL-c (15.0 vs. 10.4 mg/dL; P=0.011) and ApoA1 (0.18 vs. 0.08 g/L; P<0.0001) but not ApoB (0.02 vs. 0.02 g/L) compared with ATZ/r treatment. ATZ/r use was associated with higher mean TG increases (27.80 vs. 0.02 mg/dL; P=0.0001). Significantly greater mean decreases in TC:HDL-c and ApoB/ApoA ratios were observed with NVP vs. ATZ/r (P=0.0001 and P=0.008, respectively). Framingham CR scores were low and comparable between the arms, with only a slight mean increase from baseline to week 48 of 0.70 for NVP and 0.80 for ATZ/r [difference -0.069; 95% confidence interval (CI) -0.61 to 0.46; P=0.80].. In ARV-naïve patients with low CR at the outset, NVP showed a potentially less atherogenic lipid profile compared with ATZ/r.

Topics: Adenine; Anti-HIV Agents; Atazanavir Sulfate; Deoxycytidine; Drug Therapy, Combination; Dyslipidemias; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Lipids; Male; Nevirapine; Oligopeptides; Organophosphonates; Pyridines; Ritonavir; Tenofovir; Viral Load

Antiretroviral therapy is associated with metabolic complications, including dyslipidaemia, body fat changes and insulin resistance. Healthy volunteer studies have demonstrated a decrease in glucose disposal associated with dosing with specific antiretrovirals.. HIV-type-1-positive male participants were randomized to receive tenofovir disoproxil fumarate and lamivudine, with either fosamprenavir (FPV)/ritonavir or lopinavir (LPV)/ritonavir twice daily. A hyperinsulinaemic euglycaemic clamp was performed at baseline and at 2 weeks after commencing treatment. The homeostasis model assessment index for insulin resistance (HOMA-IR) was also calculated at these time points. Changes in lipids and lipoprotein subfractions (by nuclear magnetic resonance spectroscopy) were assessed. A pharmacokinetic assessment was undertaken at week 2.. A total of 27 participants were enrolled. There was no significant change in whole-body insulin sensitivity or HOMA-IR from baseline or between groups. Total cholesterol increased significantly, by 6.6% with FPV and 10.9% with LPV. The changes in lipids and lipoprotein subfractions were similar between groups with increases in triglycerides, very low-density lipoprotein (VLDL) and chylomicrons, and low-density lipoprotein (LDL) particles. Although the total high-density lipoprotein (HDL) particles were not significantly altered, a decrease in small HDL particles was seen. Changes in VLDL and chylomicron particles in both groups and triglycerides and small HDL particles in the LPV group were statistically significant.. In HIV-type-1-positive men initiating antiretroviral therapy with FPV- or LPV-based regimens, there were no significant changes in whole-body insulin sensitivity after 2 weeks. A proatherogenic lipid profile characterized by increases in triglycerides, VLDL and chylomicron particles and LDL particles, and a decrease in small HDL particles, was observed in both groups.

Topics: Adenine; Adipose Tissue; Adult; Anti-HIV Agents; Blood Glucose; Carbamates; Confidence Intervals; Drug Administration Schedule; Drug Combinations; Dyslipidemias; Furans; HIV Infections; HIV-1; Humans; Insulin; Insulin Resistance; Lamivudine; Lipids; Lopinavir; Male; Organophosphates; Organophosphonates; Pyrimidinones; Ritonavir; Sulfonamides; Tenofovir

The ARTEMIS study compared the efficacy of darunavir/ritonavir at once-daily doses of 800/100 mg versus once- or twice-daily doses of lopinavir/ritonavir, together with 300 mg of tenofovir and 200 mg of emtricitabine, both in once-daily doses, in treatment-naive patients. The results at 48 weeks show that darunavir/ritonavir is not inferior to lopinavir/ritonavir; the increase in CD4 count observed with both regimens was similar. Darunavir/ritonavir was superior to lopinavir/ritonavir in patients with high viral loads (>100,000 copies/mL). The use of darunavir/ritonavir was associated with a lower proportion of grades 2-4 adverse effects, especially gastrointestinal effects such as diarrhea and with a lower frequency of lipidic adverse effects, such as increased triglyceride and total cholesterol levels. Once-daily darunavir/ritonavir may be an option in first-line antiretroviral therapy, with the added advantage of a reduced dose of ritonavir and high efficacy in patients with elevated viral loads.

Topics: Adult; CD4 Lymphocyte Count; Darunavir; Drug Therapy, Combination; Dyslipidemias; Female; Gastrointestinal Diseases; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Pyrimidinones; Ritonavir; RNA, Viral; Sulfonamides; Viral Load

Treatment of human immunodeficiency virus (HIV) with protease inhibitors (PIs) is associated with insulin resistance, triglyceride-rich dyslipidemia, and fat redistribution. Atazanavir (ATV), a potent once-daily PI, has been recognized for its convenience to patients, and some studies describe improved lipid metabolism. However, its effects on insulin sensitivity have not been elucidated. We conducted this study to test the hypothesis that ATV improves insulin resistance and dyslipidemia.. We prospectively studied 9 HIV-infected men with dyslipidemia (median age, 53 years; baseline triglyceride level, >200 mg/dL) on stable PI-containing antiretroviral therapy who elected to change PI therapy to ritonavir-boosted ATV therapy, dose of 300/100 mg. We measured insulin resistance at baseline and after 12 weeks of therapy using a hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m minute). Fasting lipid profiles and body composition (whole-body dual energy x-ray absorptiometry) were also measured at baseline and after 12 weeks.. All 9 patients completed the study and maintained undetectable viral loads (<50 copies/mL) and stable CD4 counts. After 12 weeks, insulin sensitivity significantly improved (+28%; P = 0.008) in all patients. Triglyceride levels also improved.. Using the gold-standard euglycemic clamp, ritonavir-boosted ATV therapy improved PI-induced insulin resistance among dyslipidemic HIV-infected men on PI-based antiretroviral therapy. These findings were not attributable to a change in body weight and provide further evidence for ATV's unique metabolic profile among the PIs.

Topics: Adult; Aged; Atazanavir Sulfate; Body Composition; Dyslipidemias; HIV Infections; HIV Protease Inhibitors; Humans; Insulin Resistance; Male; Middle Aged; Oligopeptides; Prospective Studies; Pyridines; Ritonavir; Treatment Outcome; Triglycerides

Topics: Adult; CD4 Lymphocyte Count; Cholesterol; Cohort Studies; Drug Therapy, Combination; Dyslipidemias; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lopinavir; Pyrimidinones; Retrospective Studies; Ritonavir; Treatment Outcome; Triglycerides; Viral Load

Over the month of April, Spain has become the European country with more confirmed cases of COVID-19 infection, after surpassing Italy on April 2nd. The community of Castile and León in Spain is one of the most affected by COVID-19 infection and the province of León has a total of 3711 cases and 425 deaths so far. Rheumatic patients should be given special attention regarding COVID-19 infection due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies. Studying epidemiological and clinical characteristics of patients with rheumatic diseases infected with SARS-CoV2 is pivotal to clarify determinants of COVID-19 disease severity in patients with underlying rheumatic disease.. To describe epidemiological characteristics of patients with rheumatic diseases hospitalized with COVID-19 and determine risk factors associated with mortality in a third level Hospital setting in León, Spain.. We performed a prospective observational study, from 1st March 2020 until the 1st of June including adults with rheumatic diseases hospitalized with COVID-19 and performed a univariate and multivariate logistic regression model to estimate ORs and 95% CIs of mortality. Age, sex, comorbidities, rheumatic disease diagnosis and treatment, disease activity prior to infection, radiographic and laboratorial results at arrival were analysed.. During the study period, 3711 patients with COVID-19 were admitted to our hospital, of whom 38 (10%) had a rheumatic or musculoskeletal disease. Fifty-three percent were women, with a mean age at hospital admission of 75.3 (IQR 68-83) years. The median length of stay was 11 days. A total of 10 patients died (26%) during their hospital admission. Patients who died from COVID-19 were older (median age 78.4 IQR 74.5-83.5) than those who survived COVID-19 (median age 75.1 IQR 69.3-75.8) and more likely to have arterial hypertension (9 [90%] vs 14 [50%] patients; OR 9 (95% CI 1.0-80.8), p 0.049), dyslipidaemia (9 (90%) vs 12 (43%); OR 12 (95% CI 1.33-108), p 0.03), diabetes ((9 (90%) vs 6 (28%) patients; OR 33, p 0.002), interstitial lung disease (6 (60%) vs 6 (21%); OR 5.5 (95% CI 1.16-26), p 0.03), cardiovascular disease (8 (80%) vs 11 (39%); OR 6.18 (95% IC 1.10-34.7, p 0.04) and a moderate/high index of rheumatic disease activity (7 (25%) vs 6(60%); OR 41.4 (4.23-405.23), p 0.04). In univariate analyses, we also found that patients who died from COVID-19 had higher hyperinflammation markers than patients who survived: C-reactive protein (181 (IQR 120-220) vs 107.4 (IQR 30-150; p 0.05); lactate dehydrogenase (641.8 (IQR 465.75-853.5) vs 361 (IQR 250-450), p 0.03); serum ferritin (1026 (IQR 228.3-1536.3) vs 861.3 (IQR 389-1490.5), p 0.04); D-dimer (12,019.8 (IQR 843.5-25,790.5) vs 1544.3 (IQR 619-1622), p 0.04). No differences in sex, radiological abnormalities, rheumatological disease, background therapy or symptoms before admission between deceased patients and survivors were found. In the multivariate analysis, the following risk factors were associated with mortality: rheumatic disease activity (p = 0.003), dyslipidaemia (p = 0.01), cardiovascular disease (p = 0.02) and interstitial lung disease (p = 0.02). Age, hypertension and diabetes were significant predictors in univariate but not in multivariate analysis. Rheumatic disease activity was significantly associated with fever (p = 0.05), interstitial lung disease (p = 0.03), cardiovascular disease (p = 0.03) and dyslipidaemia (p = 0.01).. Our results suggest that comorbidities, rheumatic disease activity and laboratorial abnormalities such as C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), serum ferritin elevation significantly associated with mortality whereas previous use of rheumatic medication did not. Inflammation is closely related to severity of COVID-19. Key Points • Most patients recover from COVID-19. • The use of DMARDs, corticosteroids and biologic agents did not increase the odds of mortality in our study. • Rheumatic disease activity might be associated with mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Drug Combinations; Dyslipidemias; Female; Ferritins; Fibrin Fibrinogen Degradation Products; Hospitalization; Humans; Hydroxychloroquine; Hypertension; Interleukin 1 Receptor Antagonist Protein; L-Lactate Dehydrogenase; Length of Stay; Lopinavir; Lung Diseases, Interstitial; Male; Mortality; Odds Ratio; Pandemics; Pneumonia, Viral; Prospective Studies; Rheumatic Diseases; Risk Factors; Ritonavir; SARS-CoV-2; Severity of Illness Index; Spain

Antiretroviral therapy (ART) is associated with lipid abnormalities that contribute to increased risk of cardiovascular (CV) events among patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Although disorders of lipid metabolism associated with ART have been described before in developed countries, data on lipid profile disorders associated with ART use in China are limited. This study aimed to examine the changes in lipid profile among patients with HIV/AIDS who initiated lopinavir/ritonavir LPV/r or efavirenz (EFV)-based antiretroviral treatment regimens, which continue to be widely used China and other developing countries.. This is a retrospective, matched case-control study of HIV-positive patients initiating either LPV/r or EFV regimens at the Beijing You'an Hospital, Capital Medical University between July 2012 and January 2017. Generalized estimating equations were used to compare the differences in total cholesterol [TC], triglycerides [TG], low-density lipoprotein-cholesterol [LDL-C], and highdensity lipoprotein-cholesterol [HDL-C] at baseline and up to 24-months after ART initiation between the two treatment arms.. Baseline characteristics, including age, sex, CD4 cell count, viral load, and serum lipids, which were comparable between the two groups. The LPV/r-based regimen group had increased TC, TG, HDL-C, and LDL-C after 24-months of treatment. In the EFV-regimen group, TC, HDL-C, and LDL-C were increased compared to baseline, while the TC/HDL-C ratio decreased, and TG did not change significantly. After 24-months of treatment, the percentage of patients with dyslipidemia in the LPV/r group was much higher than in the EFV group (84.0% vs. 52.6%, P<0.001), and 17(10%) patients on LPV/r-based regimens had severe dyslipidemia. Patients on LPV/r-based regimens were at increased odds of hypercholesterolemia (odds ratio [OR]=1.709, P=0.038), hypertriglyceridemia (OR=4.315, P<0.001), and high TC/HDL-C ratio (OR=1.951, P=0.003). However, no significant difference was found in HDL-C (OR=1.246, P=0.186) or LDL-C (OR=1.253, P=0.410) between the treatment groups.. Both LPV/r or EFV treatment regimens impacted patients' lipid profiles. Compared to EFV-based regimens, patients on LPV/r-based regimens had increased odds of dyslipidemia, such as hypercholesterolemia, hypertriglyceridemia, or high TC/HDL-C ratio; however, there was no obvious effect on LDL-C, which is more relevant to the development of the cardiovascular disease.

Topics: Adult; Aged; Aged, 80 and over; Alkynes; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Asian People; Beijing; Benzoxazines; Case-Control Studies; Cyclopropanes; Drug-Related Side Effects and Adverse Reactions; Dyslipidemias; Female; HIV Infections; Hospitals, University; Humans; Lipids; Lopinavir; Male; Middle Aged; Retrospective Studies; Ritonavir; Treatment Outcome

Dyslipidaemia is common in perinatally HIV-infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs.. We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TC:HDL-C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)- or darunavir/ritonavir (DRV/r)-based antiretroviral therapy (ART) from an older PI-based ART and those remaining on an older PI. Generalized estimating equation models were fitted to assess the association of a switch to ATV/r- or DRV/r-based ART with the rate of change in lipids, adjusted for potential confounders.. From 2007 to 2014, 47 PHIV children/adolescents switched to ATV/r or DRV/r, while 120 remained on an older PI [primarily lopinavir/r (72%) and nelfinavir (24%)]. Baseline age ranged from 7 to 21 years. After adjustment for age, Tanner stage, race/ethnicity, and HIV RNA level, a switch to ATV/r or DRV/r was associated with a more rapid annual rate of decline in the ratio of TC:HDL-C. (β = -0.12; P = 0.039) than remaining on an older PI. On average, TC declined by 4.57 mg/dL/year (P = 0.057) more in the switch group. A switch to ATV/r or DRV/r was not associated with the rate of HDL-C, LDL-C, or TG change.. A switch to ATV/r or DRV/r may result in more rapid reduction in TC and the TC:HDL-C ratio in PHIV youth, potentially impacting long-term cardiovascular disease risk.

Topics: Adolescent; Atazanavir Sulfate; Child; Cohort Studies; Darunavir; Drug Therapy, Combination; Dyslipidemias; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lipids; Longitudinal Studies; Male; Ritonavir; Viral Load; Young Adult

Cobicistat seems to have a low rate of adverse events compared with ritonavir.. This restrospective observational study to evaluated changes in lipid parameters and the percentage of subjects with dyslipidemia in virologically suppressed HIV-infected patients who were receiving a regimen containing darunavir/ritonavir and were then switched from ritonavir to cobicistat, carried out from December 2015 to May 2016, included 299 HIV-1-infected patients who were on stable antiretroviral treatment including darunavir/ritonavir (monotherapy, bitherapy or triple therapy for at least 6 months) and were then switched from ritonavir to cobicistat. Lipid parameters, as well as plasma HIV-1 RNA and CD4 cell counts, were recorded at baseline just before the switch, and 24 weeks after the switch. Patients were stratified according to the presence of hypercholesterolaemia [baseline total cholesterol > 200 mg/dL and/or low-density lipoprotein (LDL) cholesterol > 130 mg/dL] or hypertriglyceridaemia (baseline triglyceride levels > 200 mg/dL).. Two hundred and ninety-nine patients were enrolled in the study. Fifty-two per cent of the total study population showed dyslipidaemia at baseline. All patients maintained HIV-1 RNA ≤ 50 HIV-1 RNA copies/mL at week 24. No statistically significant changes were seen in CD4 T-cell count from baseline to week 24 [654 (298) to 643 (313) cells/μL; P = 0.173]. When patients were stratified according to the presence of hypercholesterolaemia at baseline (n = 124), significant changes were observed in total cholesterol (P < 0.001), LDL cholesterol (P = 0.047), high-density lipoprotein (HDL) cholesterol (P = 0.002) and triglyceride levels (P = 0.025), and when they were stratified according to the presence of hypertriglyceridaemia at baseline (n = 64), changes from baseline to week 24 in triglyceride level were statistically significant [median (interquartile range) 352 (223, 389) mg/dL at baseline and 229 (131, 279) mg/dL at week 24; P < 0.001].. Cobicistat as a booster of darunavir in HIV-infected subjects had a beneficial effect on the lipid profile in patients with hypercholesterolaemia or hypertrigliceridaemia at baseline.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cobicistat; Drug Substitution; Dyslipidemias; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Retrospective Studies; Ritonavir; RNA, Viral; Treatment Outcome; Triglycerides; Viral Load

Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles.. We investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%).. 43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77-555], 548 [206-902], 793 [440-1164], 768 [494-1527] and 1491 [1122-1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266-1148], and 1098 [631-1238] ng/mL, respectively) (p<0.001), as compared with patients with no ATV-related complications (218 [77-541] ng/mL).. A significant proportion of patients treated with the conventional dosage of ATV (300/100) had plasma concentrations exceeding the upper therapeutic threshold. These patients that are at high risk to experience ATV-related complications may benefit from TDM-driven adjustments in ATV dosage with potential advantages in terms of costs and toxicity.

Topics: Adult; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Dyslipidemias; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hyperbilirubinemia; Male; Middle Aged; Nephrolithiasis; Ritonavir; Viral Load

Lopinavir/ritonavir (LPV/r) is associated with insulin resistance (IR). We aim to determine the prevalence of IR, dyslipidemia and their inter-relationships with adipokines in HIV-infected children treated with LPV/r-based highly active antiretroviral therapy (HAART).. Twenty-eight children were enrolled. Fasting glucose, insulin, lipid profiles, adipokines, and oral glucose tolerance tests were performed.. The prevalence of IR, pre-diabetes mellitus, and hypertriglyceridemia was 42.9(12/28), 10.7(3/28), and 75.0(21/28)% respectively. No case met the definition for diabetes mellitus (DM) and lipodystrophy. Children with IR had higher BMI z-score, triglyceride levels but unchanged leptin or adiponectin levels compared to those without IR. Longer duration of LPV/r-based HAART was associated with increased levels of triglyceride and total cholesterol.. We describe high prevalence of IR, pre-diabetes mellitus, and dyslipidemia among HIV-infected children receiving LPV/r-based HAART. Pre-diabetes mellitus or DM or IR screening might be important for early diagnosis and intervention in these children.

Topics: Adipokines; Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Blood Glucose; Child; Child, Preschool; Dyslipidemias; Female; HIV Infections; Humans; Insulin Resistance; Lipids; Lopinavir; Male; Pregnancy; Ritonavir; Thailand

Drugs like statins may induce rhabdomyolysis. Simvastatin and lovastatin have a high hepatic metabolism and their potential toxicity could be increased by interactions with other drugs that reduce their metabolism.. A case-report is presented of an HIV-infected patient treated with antiretroviral drugs who developed a rhabdomyolysis-induced renal failure and liver toxicity when simvastatin was substituted for atorvastatin. A literature review is also presented.. The patient required hospital admission and showed a favorable response after hydration and urine alkalinization. There were 4 additional cases published of which there was one death.. Drug-drug interactions can increase the risk of statin induced rhabdomyolysis. In order to evaluate them properly, physicians at all levels of clinical care should be aware of all drugs prescribed to their patients and the contraindicated combinations.

Topics: Antiretroviral Therapy, Highly Active; Atorvastatin; Chemical and Drug Induced Liver Injury; Comorbidity; Contraindications; Cost-Benefit Analysis; Cytochrome P-450 CYP3A Inhibitors; Drug Substitution; Drug Synergism; Dyslipidemias; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Tubular Necrosis, Acute; Middle Aged; Rhabdomyolysis; Ritonavir; Simvastatin

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro-immunological parameters, triglycerides (TGs), total cholesterol (TCh), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting glucose, HOMA-IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles.

Topics: Adult; Anti-HIV Agents; Blood Chemical Analysis; Carbamates; CD4 Lymphocyte Count; Darunavir; Dyslipidemias; Female; Follow-Up Studies; Furans; HIV Infections; Humans; Kidney Function Tests; Liver Function Tests; Male; Metabolome; Middle Aged; Organophosphates; Prospective Studies; Protease Inhibitors; Ritonavir; Sulfonamides; White People

Left ventricular hypertrophy (LVH) is a predictor of overall mortality in the general population. The most sensitive diagnostic method is transthoracic echocardiography (TTE). In this study, we describe the prevalence of LVH, and the factors associated with it, in a group of patients with HIV infection.. TTE was offered to all patients attending the outpatient clinic of the Hospital Costa del Sol (Marbella, Spain) between 1 December 2009 and 28 February 2011. The corresponding demographic and clinical data were obtained. The left ventricular mass (LVM) was calculated and indexed by height(2.7). LVH was defined as LVM >48g/m(2.7) in men or >44g/m(2.7) in women.. We examined 388 individuals (75.5% male, mean age 45.38years). Of these, 76.1% were receiving HAART; 11.9% had hypertension, 6.2% had diabetes mellitus, 23.2% had dyslipidaemia and 53.6% were tobacco users. The risk of cardiovascular disease at 10years (RV10) was 12.15% (95%CI: 10.99-13.31%). 19.1% of these patients had a high RV10. A total of 69 patients (19.8%) presented high LVM. Age, hypertension, dyslipidaemia, RV10 and the use of nevirapine were associated with a greater presence of LVH in the univariate analysis. In the logistic regression analysis performed, the factors retained in the model were the presence of high RV10 (OR: 2.92, 95%CI: 1.39-6.15) and the use of nevirapine (OR 2.20, 95%CI: 1.18-4.14).. In this group of patients, the use of nevirapine and the presence of high RV10 were associated with LVH. The use of nevirapine might be related to its prescription for patients with higher RV10.

Topics: Adenine; Adult; Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Carbamates; Comorbidity; Cross-Sectional Studies; Cyclopropanes; Diabetes Mellitus; Drug Combinations; Dyslipidemias; Echocardiography; Female; Furans; HIV Infections; Humans; Hypertension; Hypertrophy, Left Ventricular; Lamivudine; Lopinavir; Male; Middle Aged; Nevirapine; Organophosphates; Organophosphonates; Risk Factors; Ritonavir; Smoking; Spain; Sulfonamides; Tenofovir; Zidovudine

The complex interplay between viral infection and virus-activated inflammatory pathways with protease inhibitors (PIs) contributes to the increased risk of developing atherosclerosis and coronary artery disease in HIV-infected patients. Leflunomide is an antirheumatic drug whose administration to HIV-1-infected persons effectively decreases T-cell turnover and activation. In this study we have investigated the effects of leflunomide on dyslipidaemia and lipodistrophy induced by ritonavir in rodents.. Mice were administered ritonavir (5 mg/kg/day) alone or in combination with leflunomide (40 mg/kg/day) for 12 days. Expression of nuclear receptor and lipidogenetic genes was measured in liver and adipose tissues.. Administration of the HIV PI ritonavir to mice increased plasma triacylglycerols, free fatty acids and cholesterol levels, and this effect was reverted by cotreatment with leflunomide. Ritonavir administration was associated with reduced epididymal fat/body weight ratio and increased liver content of triacylglycerols content. These effects were reverted by leuflunomide. Histopathology analysis shows that exposure to ritonavir causes inflammation of epididymal fat as demonstrated by dense leukocytes infiltration as well as by increased levels of proinflammatory mediators and reduced expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ). Leflunomide reduced epididymal fat inflammatory-metabolic alteration induced by ritonavir and restored PPAR-γ expression in the epididymal fat.. We have shown that the anti-inflammatory drug leflunomide protects against ritonavir-induced inflammation and dysmetabolism in adipose tissue and might be a promising strategy in the setting of HIV-infected patients at risk for HIV-induced dyslipidaemia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dyslipidemias; Epididymis; Fatty Liver; HIV Protease Inhibitors; Isoxazoles; Leflunomide; Lipodystrophy; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Ritonavir

We describe a 55-year-old HIV-1-infected male who developed severe dyslipidaemia (total cholesterol 600 mg/dl, triglycerides >5,000 mg/dl, high density lipoprotein <5 mg/dl) after raltegravir was added to his lopinavir/ritonavir-containing regimen. To our knowledge, this is the first reported case of severe dyslipidaemia associated with the addition of raltegravir to a lopinavir/ritonavir-based regimen, suggestive of a possible drug interaction. The lipid profile quickly normalized following discontinuation of lopinavir/ritonavir and continuation of raltegravir, suggesting that lopinavir/ritonavir was the primary driver for the adverse event. With increasing interest in nucleoside-sparing regimens, knowledge of clinically significant adverse events such as this is important for HIV clinicians when selecting regimens for patients with highly resistant virus or drug tolerability issues.

Topics: Cholesterol, HDL; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Middle Aged; Pyrrolidinones; Raltegravir Potassium; Ritonavir; Treatment Outcome; Triglycerides

HIV-infected patients are at an increased risk of developing cardiovascular disease. Elevated levels of C-reactive protein (CRP) are associated with an increased risk of cardiovascular disease in the general population and are reduced by statin therapy. We examined the effect of pravastatin and rosuvastatin on CRP levels in 58 dyslipidemic HIV-infected patients. A 45-day course of either statin reduced the median CRP level from 3.0 to 2.4 mg/l (P < 0.001) with no correlation with changes in lipid parameters.

Topics: Anticholesteremic Agents; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Female; HIV Infections; Humans; Male; Middle Aged; Pravastatin; Ritonavir

The authors describe an HIV-infected patient with moderate renal failure receiving combination antiretroviral therapy. Because of dyslipidaemia he was initially treated with pravastatin but developed rhabdomyolysis after a switch to rosuvastatin. With this case we illustrate that statins as well as antiretroviral therapy are susceptible to clinical relevant drug-drug or drug-disease interactions. Knowledge of these interactions is important to provide patients with the best possible care.

Topics: Anti-HIV Agents; Drug Therapy, Combination; Dyslipidemias; Fluorobenzenes; HIV Infections; HIV-1; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lopinavir; Male; Middle Aged; Pyrimidines; Pyrimidinones; Renal Insufficiency; Rhabdomyolysis; Ritonavir; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome

Topics: C-Reactive Protein; Cardiovascular Diseases; Dyslipidemias; Female; HIV Infections; Humans; Male; Pravastatin; Ritonavir

Although human immunodeficiency virus (HIV)-related morbidity and mortality rates in patients treated with a combination of high active antiretroviral therapy (HAART) have declined, significant metabolic/vascular adverse effects associated with the long term use of HIV protease inhibitors (PIs) have emerged as a significant side effect. Here we illustrate that targeting the bile acid sensor farnesoid X receptor (FXR) protects against dyslipidemia and vascular injury induced HIV-PIs in rodents.. Administration of the HIV PI ritonavir to wild type mice increased plasma triacylglycerols and cholesterol levels and this effect was exacerbated by dosing ritonavir to mice harbouring a disrupted FXR. Dyslipidemia induced by ritonavir associated with a shift in the liver expression of signature genes, Sterol Regulatory Element-Binding Protein (SREBP)-1 and fatty acid synthase. Treating wild type mice with the FXR agonist (chenodeoxycholic acid, CDCA) protected against development of dyslipidemia induced by ritonavir. Administration of ritonavir to ApoE(-/-) mice, a strain that develop spontaneously atherosclerosis, increased the extent of aortic plaques without worsening the dyslipidemia. Treating these mice with CDCA reduced the extent of aortic plaques by 70% without changing plasma lipoproteins or the liver expression of signature genes. A beneficial effect on aortic plaques was also obtained by treating ApoE(-/-) mice with gemfibrozil, a PPARα agonist. FXR activation counter-regulated induction of expression/activity of CD36 caused by HIV-PIs in circulating monocytes and aortic plaques. In macrophages cell lines, CDCA attenuated CD36 induction and uptake of acetylated LDL caused by ritonavir. Natural and synthetic FXR ligands reduced the nuclear translocation of SREBP1c caused by ritonavir.. Activation of the bile acid sensor FXR protects against dyslipidemia and atherosclerotic caused by ritonavir, a widely used HIV PI. From a mechanistic stand point it appears that besides reducing the liver expression of genes involved in fatty acid synthesis, FXR activation counter-regulates the expression/activity of CD36 on monocytes. FXR ligands might hold promise in the treatment dyslipidemia induced by ritonavir.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Bile Acids and Salts; CD36 Antigens; Cell Line; Dyslipidemias; HIV Protease Inhibitors; Mice; Mice, Knockout; Receptors, Cytoplasmic and Nuclear; Ritonavir

Protease inhibitors (PIs) inhibit the cytochrome P450 CYP3A4. Because the metabolism of pravastatin is independent of the cytochrome P450 CYP3A4, this drug has become the preferred statin for treatment of dyslipidemia associated with human immunodeficiency virus (HIV) infection, with no cases of serious toxicity such as rhabdomyolysis reported to date. We report an HIV-infected patient receiving antiretroviral regimen consisting of atazanavir, ritonavir, emtricitabine and tenofovir who developed severe rhabdomyolysis approximately 4 months after increasing his pravastatin dose from 40 to 80 mg daily. His symptoms resolved within 10 days after the discontinuation of pravastatin and antiretroviral therapy. To our knowledge, this is the first case of rhabdomyolysis possibly caused by pravastatin in an HIV-infected patient.

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Deoxycytidine; Dyslipidemias; Emtricitabine; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Oligopeptides; Organophosphonates; Pravastatin; Pyridines; Rhabdomyolysis; Ritonavir; Tenofovir

To evaluate the efficacy, safety, and lipid-lowering effects after switching from a non-atazanavir-containing, protease inhibitor-based highly active antiretroviral therapy (HAART) to atazanavir-ritonavir-based HAART in patients infected with human immunodeficiency virus (HIV).. Multicenter, noncontrolled, retrospective study.. Three tertiary teaching hospitals.. Thirty-six patients with HIV infection, aged 18 years or older, who were receiving non-atazanavir-containing, protease inhibitor-based HAART that was switched to atazanavir 300 mg-ritonavir 100 mg-based HAART without changes in nucleoside reverse transcriptase inhibitors and confounders known to alter serum lipid levels.. Lipid profiles measured 4 weeks-6 months before the switch, as well as follow-up lipid profiles measured 4 weeks-6 months after receiving the new HAART regimen, were evaluated. The switch resulted in the following changes in lipid levels: total cholesterol -9% (p=0.002), low-density lipoprotein cholesterol -13% (p<0.001), high-density lipoprotein cholesterol (HDL) -2% (p=0.431), triglycerides -23% (p=0.007), non-HDL -11% (p=0.002), total cholesterol:HDL ratio -10% (p=0.004), and triglyceride:HDL ratio -24% (p=0.019). A subgroup analysis was conducted on the lipid profiles of nine patients who still met the strict inclusion and exclusion criteria up to 9 months after the switch; it showed that the reductions in their lipid profiles were sustained. In addition, 33% more patients achieved their National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III cholesterol goals. No significant changes were noted in median (interquartile range) CD4+ counts (372 [236-551] and 361 [217-464] cells/mm(3), p=0.118) or in number of patients with undetectable HIV viral loads ([defined as < 50 copies/ml] 32/36 and 31/36 patients, p>0.05) between baseline and after the switch, respectively.. Switching to an atazanavir-ritonavir-based HAART regimen was associated with significant improvement in lipid profiles, similar to those seen in clinical trials, without compromising safety or viral and immunologic control. In addition, more patients were able to achieve their NCEP ATP III goals.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Body Mass Index; Body Weight; Dyslipidemias; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lipids; Male; Metabolic Syndrome; Middle Aged; Oligopeptides; Pyridines; Retrospective Studies; Ritonavir