Recovery of fat following a switch to nucleoside reverse transcriptase inhibitor‐sparing therapy in patients with lipoatrophy: results from the 96‐week randomized ANRS 108 NoNuke Trial

Abstract

Objectives To evaluate the impact on peripheral fat tissue of a nucleoside reverse transcriptase inhibitor (NRTI)‐sparing regimen in lipoatrophic HIV‐1 infected patients. Methods This 96‐week prospective, randomized study compared lipoatrophic patients switched to an NRTI‐sparing regimen with patients remaining on an NRTI‐containing regimen. The primary endpoint was the change in thigh subcutaneous fat tissue volume between baseline and week 48, as assessed by computerized tomography. Results One hundred patients were included, 50 in each arm. At baseline, patients had been on highly active antiretroviral therapy (HAART) for a median time of 6.6 years (4.9–9.7); 71% of the patients had received thymidine analogues [stavudine (37%), zidovudine (34%)]. The mean change in fat volume between baseline and week 48 significantly favoured the NRTI‐sparing arm over the NRTI‐maintaining arm in the intent‐to‐treat analysis, with a last‐observation‐carried‐forward approach [+34 cm³; 95% confidence interval (CI) 5–63 cm³; P=0.002]. This was confirmed in the intent‐to‐treat analysis of available data, with a mean difference of +109 cm³ (95% CI 34–185 cm³) at week 96 (n=53; P=0.001). This corresponded to increases of 12 and 30% in fat volume at weeks 48 and 96, respectively, in the NRTI‐sparing arm. Conclusions Switching from an effective NRTI‐containing regimen to an NRTI‐sparing regimen preserves immunovirological status and increases subcutaneous fat volume at weeks 48 and 96.