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Atazanavir: Evaluation of Body Changes and Lipids/Glucose After 48 weeks Treatment
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Joseph Jemsek (Jemsek Clinic, Huntersville, NC) reported body effects of atazanavir (Reyataz) and efavirenz each combined with fixed dose AZT and 3TC from the BMS 034 study. These are data after 48 weeks from the Metabolic Substudy of 034. Atazanavir (ATV) is a new protease inhibitor that was approved by the FDA recently and is just being made available in pharmacies between now and July 16. ATV is taken once a day with 2 pills (400 mg). So far in studies ATV has not shown elevations in cholesterol, tryglicerides, and glucose.
The purpose of the substudy is to evaluate body fat redistribution in antiretroviral-na•ve patients treated with the study drugs. In the metabolic substudy, dual-energy x-ray absorptiometry and cross-section computerized tomography scans were performed at baseline and week 48. The testing used to evaluate body changes are: CT scans (computerized tomography) and DEXA (dual energy x-ray absorptiometry. The body changes evaluated are visceral adipose tissue (VAT, belly fat), subcutaneous fat (SAT, peripheral fat: legs, arms, face), total adipose tissue (TAT), appendecular fat (limbs), truncal fat, trunk is between hips and shoulders), and total body fat.
Analyses included all patients with assessments prior to dosing initiation and after 24 weeks. Dual-energy x-ray absorptiometry and cross-section computerized tomography scans were performed at baseline and week 48. Patients who discontinued after week 24: last observation was carried forward. Centralized readings were performed at Tufts University. BMS study 034 was a randomized, double-blind, controlled study where 810 treatment-na•ve patients were randomized to ATV 400 mg once daily vs efavirenz (EFV, Sustiva) 600 mg once daily, and fixed dose AZT/3TC was given to all patients. The Metabolic Substudy included 111 patients receiving ATV and 100 receiving EFV.
Baseline characteristics, including age, HIV RNA level, CD4 count, and body mass index, were consistent between the substudy participants and the overall study population (N=805). CD4 counts were 320, BMI was 23.6 kg/m2, HIV-RNA was 4.70 log. Only about 33% of patients in 034 were White.
RESULTS
BODY CHANGES
After 48 weeks on ATV or EFV there was no fat loss. After 48 weeks on therapy the DEXA results showed no loss of fat in the body compartments examined for either EFV or ATV treatment arms: appendicular, truncal, total fat. There were Increases in fat from baseline (mean percent) at week 48 were observed for appendicular (3%, atazanavir; 3%, efavirenz), truncal (5%, atazanavir; 8%, efavirenz), and total body fat (5%, atazanavir; 5%, efavirenz) as well as for visceral (40%, atazanavir; 29%, efavirenz), subcutaneous (19%, atazanavir; 5%, efavirenz), and total adipose tissue (23%, atazanavir; 11%, efavirenz). Similar results were seen, slight increases in fat, using CT scans for VAT, SAT, and TAT and there were no significant differences between treatment arms. Mean weight gain from baseline at week 48 was ATV 2 kg and EFV 0 kg.
LIPIDS
There were no increases for patients on ATV for total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. For patients on EFV, there were increases in total cholesterol (from about 150 to 180 mg/dL), LDL-cholesterol (from about 90 to 110 mg/dL), HDL-cholesterol (from about 40 to 50 mg/dL), and triglycerides (from about110 to 140 mg/dL).
FASTING GLUCOSE & FASTING INSULIN
For patients taking ATV fasting glucose increased from 93 to 97 mg/dL, and fasting insulin went from 12.9 uU/mL to 12.5 uU/mL. For patients taking EFV fasting glucose went from 91 to 94 mg/dL and fasting insulin from 10 to 11.3 mg/dL.
The study authors concluded that ATV and EFV are associated with comparable effects through week 48. There was no evidence of belly central adiposity by VAT or TAT and no evience of lipoatrophy at week 48. There were no increases in lipids or insulin resistance for patients taking ATV, and patients taking EFV saw some increases in lipids. Neither ATV or EFV resulted in increases in insulin resistance.
It's encouraging that no body changes were reported after 48 weeks on ATV, but longer follow-up is needed to evaluate the effect of ATV on body changes. During the question and answer period following the oral presentation for this study Jemsek said that they would continue follow-up for patients receiving ATV until 96 weeks. Therefore, we should be better able to evaluate body changes because follow-up of 48 weeks is not adequate to reasonably evaluate the effect of ATV on body changes.
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