• An Open Randomized Study on the Replacement of HIV-1 Protease Inhibitors by Efavirenz in Chronically Suppressed HIV-1-Infected Patients with Lipodystrophy (Poster 668)
  Authored by E. Martinez, J. Romeu, M. A. Garcia-Viejo, L. Cruz, J. L. Blanco, E. Negredo, B. Clotet, and J. M. Gatell
  View the original abstract

Numerous studies examining protease inhibitor-substitution strategies have been undertaken, but many of them are single-armed (i.e., all patients switch) and therefore provide less meaningful data. In this Spanish study, patients with lipodystrophy were randomized to continue their present PI or substitute efavirenz, with the major outcomes of interest being continued viral load suppression, changes in lipodystrophy, and metabolic parameters.

Ninety-three patients enrolled, with 47 continuing their PI and 46 switching. To be eligible, the patients had to have had a viral load <200 for more than six months and have noted a change in their body shape. Most of the patients were receiving either nelfinavir or indinavir as their PI.

After 12 months of the study, 17% of the PI group and 33% of the lipodystrophy had experienced virologic failure (defined by viral load >200), a difference that was nearly statistically significant (p=0.08) and largely due to an unusually high adverse events rate to efavirenz. Efavirenz treatment significantly reduced insulin levels, waist-hip ratio, and increased HDL cholesterol compared with continued PI. Patients reported improvements in body habitus, but by objective criteria (ultrasound) the only area with a significant change was in central adiposity, where the PI group continued to show progressive increases in visceral fat, while the efavirenz group had a decline. Both treatment arms had progression of subcutaneous fat atrophy.

The results of this study differ somewhat from other randomized trials of NNRTI substitution, which have generally shown that substituting this drug for the PI is associated with stable or improved virologic outcome. Nonetheless, it confirms that this strategy does improve several of the metabolic parameters (in particular insulin resistance) even if effects on body habitus changes are more modest.