Body weight was measured
at baseline and at weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48, and anthropometric measurements of the waist and hips were taken at baseline and at weeks 24 and 48, for all patients enrolled in the TORO studies. Additional body composition assessments were undertaken in a subgroup of trial participants (see below and Fig. 1). Fasting (minimum 8 h) serum levels of glucose, total cholesterol, triglyceride, C-peptide, insulin, and low-density lipoprotein (LDL) (calculated), high-density lipoprotein (HDL) and very low density H 89 nmr lipoprotein (VLDL) cholesterol were determined at baseline and at weeks 8, 16, 24, 32 and 48 for all patients. All chemistry samples were analysed at a central laboratory (Covance Central Laboratory Services, Indianapolis, IN for TORO 1; Covance Central Laboratory Services, Geneva, Switzerland for TORO 2) using a validated automated analyser. Body imaging parameters were evaluated in a subset of TORO patients who consented to these assessments at sites capable of performing the scans (enfuvirtide Nutlin-3a datasheet group, n=102; control group,
n=53). Whole-body dual-energy X-ray absorptiometry (DEXA) scans and single-slice abdominal computed tomography (CT) scans at the level of the L4 vertebra were performed at baseline, and on those substudy patients who had not ‘switched’ at weeks 24 and 48. Based on
the DEXA scans, peripheral fat tissue estimates were made for left and right arms and legs where possible (some sites used a DEXA scanner that only scanned the left side of the body) and estimations of truncal fat mass and truncal lean mass were made. CT scans were used to estimate levels of subcutaneous, visceral and total adipose tissue (SAT, VAT and TAT, respectively). Total fat measurements were interpreted as the sum of VAT and SAT measurements. The DEXA and CT scans were assessed at a central Carbachol laboratory (Synarc Inc., San Francisco, CA, USA). The reader was blinded to the patient’s regimen. This study was planned to include descriptive analyses only. Post hoc statistical analyses were performed to determine the 95% confidence intervals (CIs) for the differences found between the treatment groups at 48 weeks. Differences were considered significant (equivalent to a P-value of <0.05) if the 95% CI did not span 0. Across the two TORO trials, 997 patients were randomized and treated, and had at least one follow-up safety measurement performed (enfuvirtide group, n=663; control group, n=334). Baseline demographic, virological and immunological characteristics of the patients are summarized in Table 1. TORO study subjects had a median of 7 (range 1–16) years of ARV experience and had been exposed to a median of 12 ARVs (range 6–19) .