abacavir and Hyperlipidemias

Topics: Acquired Immunodeficiency Syndrome; Cross-Sectional Studies; Dideoxynucleosides; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Female; HIV Infections; Humans; Hyperlipidemias; Incidence; Lamivudine; Lipodystrophy; Male; Randomized Controlled Trials as Topic; Risk Assessment

To assess the potency, efficacy and toxicity of abacavir/lamivudine (ABC/3TC) versus tenfovir/emcitrabine (TDF/FTC) with efavirenz (EFV) in naive patients with HIV infection a prospective observational study was carried out to evaluate immunovirological parameters every three months and metabolic parameters every six months. In all, 21 patients were enrolled (10 on ABC/3TC and 11 on TDF/FTC). Fisher's test revealed no statistically significant difference between the two arms in terms of immunological recovery and control of viral replication. For metabolic parameters at week 48 no statistically significant differences were noted between the two arms. The two ABC/3TC and TDF/FTC backbones showed the same potency; ABC had a more negative impact on metabolic parameters without statistical power.

Topics: Adenine; Adult; Alkynes; Anti-HIV Agents; Benzoxazines; CD4 Lymphocyte Count; Cyclopropanes; Deoxycytidine; Dideoxynucleosides; Drug Therapy, Combination; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Hyperinsulinism; Hyperlipidemias; Lamivudine; Male; Middle Aged; Mutation; Organophosphonates; Prospective Studies; Tenofovir; Thymidine; Treatment Outcome; Young Adult

Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects.. An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors.. At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments.. In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cholesterol; Dideoxynucleosides; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hyperlipidemias; Least-Squares Analysis; Lipids; Male; Middle Aged; Pilot Projects; Reverse Transcriptase Inhibitors; Triglycerides

The mechanisms by which dyslipidemia and lipoatrophy develop during antiretroviral therapy are not clear. No treatment of lipoatrophy is currently established.. This was an open-label randomized study of HIV-positive individuals on a first-line therapy containing stavudine (d4T) with either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) and with hypercholesterolemia (defined as total cholesterol >5.2 mmol/L or >180 mg/dL) and/or lipoatrophy and with a viral load of <50 copies/mL. Patients switched d4T to abacavir (ABC) (group 1), a PI or NNRTI to ABC (group 2), or d4T and PI or NNRTI to ABC plus AZT (group 3). Patients were followed-up with fasting blood levels, dual-energy X-ray absorptiometry (DXA), and computed tomography (CT) scans for 48 weeks.. Thirty patients were included, with 27 completing 48 weeks of therapy. One ABC hypersensitivity reaction was the only serious adverse event. All patients' viral loads remained at <50 copies/mL. CD4 cell counts rose in groups 2 and 3 but fell modestly in group 1. Total and low-density lipoprotein cholesterol improved significantly in groups 2 and 3. Triglycerides fell significantly in group 2. In contrast, total, arm, and leg fat mass (by DXA) rose significantly in group 1 but fell modestly in groups 2 and 3. Visceral adiposity (by CT scan) was unaffected in all groups.. Abacavir represents a virologically effective replacement for d4T, PI, or NNRTI in persons on successful first-line therapy. Replacement of a PI or NNRTI with ABC leads to modest improvement in both cholesterol and triglycerides. Replacement of d4T with ABC leads to modest improvements in fat mass.

Topics: Adult; Body Composition; Dideoxynucleosides; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-Associated Lipodystrophy Syndrome; Humans; Hyperlipidemias; Insulin Resistance; Male; Reverse Transcriptase Inhibitors; Stavudine; Time Factors

Topics: Anti-HIV Agents; Clofibric Acid; Dideoxynucleosides; Drug Hypersensitivity; Drug Interactions; Drug Therapy, Combination; Fibric Acids; HIV Infections; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Rhabdomyolysis