indinavir-sulfate and Hypercholesterolemia

To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent.. We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a

Topics: Bezafibrate; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Hypolipidemic Agents; Indinavir; Lipids; Retrospective Studies; Ritonavir; Saquinavir

To evaluate the efficacy and safety of indinavir/ritonavir 400/100 mg plus stavudine and lamivudine twice daily in antiretroviral-therapy-naive Thai HIV-1-infected patients.. This was an open-label, non-randomized single arm study. Antiretroviral-naive patients (n=80) with CD4+ cell count < 200 x 10(6)/l were started on stavudine and lamivudine plus indinavir/ritonavir 400/100 mg twice daily. CD4+ cell count and HIV RNA were determined at week 0, 12, 24, 48 and 96. HIV RNA was measured to a level of 50 copies/ml by RT-PCR assay. Primary analysis was statistically performed as intent to treat. The primary endpoint was the percentage of patients with plasma HIV RNA below 50 copies/ml at week 96.. Eighty antiretroviral-therapy-naive patients with median CD4+ cell count 19 x 10(6)/l (range: 2 - 197 x 10(6)/l) and median baseline plasma HIV RNA of 174,000 copies/ml (range 16,800-750,000 copies/ml) were enrolled. In the intent-to-treat analysis at week 96, the proportion of patients with HIV RNA of <50 copies/ml was 68.8% (95% confidence interval [CI]: 68.3-69.3), whereas it was 88.7% (95% CI: 88.1-89.3) in the on-treatment analysis at week 96. The regimen was well tolerated. Hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia were found in 8.3, 33.3 and 37.0% of the patients, respectively. Treatment was stopped in 18 patients; two from intolerance, two switched therapy, four as a result of serious adverse event-related death, and ten were lost to follow-up.. Our study demonstrates that indinavir/ritonavir 400/100 mg plus stavudine and lamivudine twice daily, the least expensive boosted protease inhibitor, appears to be effective and safe up to 96 weeks despite high baseline viraemia and low CD4+ cell count in antiretroviral-naive patients.

Topics: Administration, Oral; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Drug Administration Schedule; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Indinavir; Lamivudine; Male; Ritonavir; RNA, Viral; Stavudine; Thailand; Treatment Outcome; Viral Load; Withholding Treatment

Lipoprotein disorders in HIV-positive patients receiving highly active antiretroviral therapy (HAART) are becoming a major concern in HIV treatment, since there is growing evidence for an association between HAART-induced hyperlipidemia and increased cardiovascular risk. Yet relatively few data are available on the possible interactions of HAART and treatment with statins.. In this prospective study, 25 HIV-positive, treatment-experienced patients (five female, 20 male, all Caucasian) were treated with either fluvastatin or pravastatin. Total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels, and serum triglycerides were determined at regular intervals, as well as therapeutic drug monitoring to assess possible drug interactions.. In 13 pravastatin-treated patients, a decrease in total cholesterol levels (from 7.12 mmol/l to 6.29 mmol/l) after 12 weeks of therapy was seen. In 12 patients treated with fluvastatin, a permanent reduction of total cholesterol (from 6.46 mmol/l to 5.31 mmol/l) after 12 weeks was observed. The reduction of LDL levels was 30.2% in the fluvastatin group and 14.4% in the pravastatin group. In eight patients receiving an indinavir-containing HAART, indinavir plasma levels were not significantly influenced. No effect on triglycerides or HDL was observed.. Fluvastatin and pravastatin are efficient in lowering total and LDL cholesterol levels in HIV-positive patients receiving HAART. Furthermore, no influence on indinavir plasma levels could be observed. Therefore, both compounds seem to be a viable treatment option in HAART-induced hypercholesterolemia.

Topics: Adult; Anticholesteremic Agents; Antiretroviral Therapy, Highly Active; Fatty Acids, Monounsaturated; Female; Fluvastatin; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Indinavir; Indoles; Male; Middle Aged; Pravastatin; Prospective Studies; Treatment Outcome

There is no standard treatment of HIV-infected patients who fail protease inhibitor (PI)-containing antiretroviral therapy. This open-label, noncomparative 24-week study with a 24-week extension evaluated the efficacy, safety, and tolerability of twice-daily indinavir/ritonavir 800/200 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) in this population. Presented here are the results of the 24-week study. Patients were HIV-infected adults who had prior viral RNA (vRNA) suppression (<400 copies/mL), subsequent failure (> or =400 and < or =100,000 copies/mL) on antiretroviral therapy, and at least one new NRTI available for treatment. The proportions of patients achieving plasma vRNA <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat (ITT) models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Mean changes from baseline in vRNA and CD4 cell count were evaluated using DAO and an ITT mixed-model approach. Sixty-three patients (87% male) with a mean age of 42 years and mean baseline vRNA and CD4 cell counts of 3.8 log(10) copies/mL and 360 cells/mm(3), respectively, were enrolled. The proportion (95% confidence interval) of patients achieving vRNA <400 and <50 copies/mL at week 24 were 76% (61%, 87%) and 50% (35%, 65%) for DAO, 64% (50%, 75%) and 43% (30%, 56%) for GEE, and 56% (43%, 68%) and 37% (25%, 50%) for NC = F, respectively. At Week 24, baseline vRNA decreased by >1.0 log(10) copies/mL and CD4 cell counts increased by approximately 90 cells/mm(3). Three patients (5%) experienced serious drug-related adverse events. Seven patients (11%) discontinued treatment due to clinical or laboratory adverse events. In this study, the enhanced, twice-daily regimen of indinavir/ritonavir 800/200 mg plus 2 NRTIs provided suppression of HIV in many patients who had failed a PI-containing regimen and was generally well tolerated.

Topics: Acidosis; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Hyperbilirubinemia; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Indinavir; Kidney Calculi; Male; Middle Aged; Ritonavir; RNA, Viral; Treatment Failure

We report a case of hypercholesterolemia that occurred 2 weeks after the start of highly active antiretroviral therapy following a needlestick exposure to human immunodeficiency virus (HIV) in an HIV-negative health care worker who was receiving thyroid replacement therapy. The elevated thyrotropic hormone level and hypercholesterolemia resolved after the antiretroviral therapy was stopped.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Drug Interactions; Female; Health Personnel; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Indinavir; Lamivudine; Nelfinavir; Occupational Exposure; Reverse Transcriptase Inhibitors; Thyroxine; Zidovudine

Since the availability of protease inhibitors in 1997, there has been a great change in antiretroviral therapy but also new long term side effects have emerged, mainly metabolic changes such as hypertriglyceridemia, hypercholesteremia and hyperglycemia. Besides, fat redistribution has been observed. Fat wastes in the face and limbs but accumulates in the adipose tissue of the dorsocervical and abdominal region and the breasts. The mechanism of these changes remains unclear. For therapy a protease inhibitor free therapy or lipid lowering drugs may be tried. 29 of our 224 patients developed lipodystrophy. 27 of these patients had been treated with a protease inhibitor (17 patients with indinavir); 2 of the patients had never received protease inhibitors.

Topics: Female; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Indinavir; Lipodystrophy; Male; Syndrome

Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Didanosine; Drug Therapy, Combination; HIV Infections; Humans; Hypercholesterolemia; Hypertriglyceridemia; Indinavir; Middle Aged; Nausea; Oxazines; Ritonavir

Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia. In this study, we characterized the lipoprotein profile in subjects receiving ritonavir, indinavir, or nelfinavir, alone or in combination with saquinavir.. Plasma lipoprotein levels were quantified in 93 HIV-infected adults receiving PIs. Comparison was done with pretreatment values and with 28 nonPI-treated HIV-infected subjects. An elevation in plasma cholesterol levels was observed in all PI-treated groups but was more pronounced for ritonavir (2.0+/-0.3 mmol/L [mean+/-SEM], n=46, versus 0.1+/-0.2 mmol/L in nonPI treated group, P<0.001) than for indinavir (0.8+/-0.2 mmol/L, n=26, P=0.03) or nelfinavir (1.2+/-0.2 mmol/L, n=21, P=0.01). Administration of ritonavir, but not indinavir or nelfinavir, was associated with a marked elevation in plasma triglyceride levels (1.83+/-0.46 mmol/L, P=0.002). Plasma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 48% increase in plasma levels of lipoprotein(a) was detected in PI-treated subjects with pretreatment Lp(a) values >20 mg/dL. Similar changes in plasma lipid levels were observed in 6 children receiving ritonavir.. Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia. The risk of pancreatitis and premature atherosclerosis due to PI-associated dyslipidemia remains to be established.

Topics: Adult; Anti-HIV Agents; Arteriosclerosis; Child; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Indinavir; Lipids; Lipoprotein(a); Lipoproteins; Logistic Models; Male; Nelfinavir; Risk Factors; Ritonavir; Saquinavir; Thyrotropin