• Poster 45: A Prospective Open-Label Pilot Trial of a Maintenance Nevirapine-Containing Regimen in Patients with Undetectable Viral Loads on Protease Inhibitor Regimens for at Least Six Months (Authored by (P. Tebas, K. Yarasheski, W.G. Powderly, E. Kane, D. Marin, J. Simpson, S. Claxton, M. Klebert, And K. Henry. Washington Univ., St. Louis, MO; and Regions Hosp., St. Paul, MN)
  Click here to view the original abstract

• Poster 47: Improvement of Lipodystrophy in HIV-1-Infected Subjects Switching from Two NRTI/PI to Two NRTI/Abacavir (Authored by W. Rozenbaum, J.M. Molina, J.F. Delfraissy, M. Bentata, P. De Truchis, and Z. Antoun. Rothschild Hosp.; Assistance Publiquê Hôpitaux de Paris; Glaxo-Wellcome, France)
  Click here to view the original abstract

• Poster 51: A Novel Use of Abacavir to Simplify Therapy in PI-Experienced Patients Successfully Treated with HAART (Authored by F.D. Goebel and R.K. Walli for the CNA30017 study team. Paig-Maximilians University, Munich, Germany)
  Click here to view the original abstract

• Slide 206: Clinical, Virological and Immunological Benefit of Switching the Protease Inhibitor by Nevirapine (NVP) in HAART-Experienced Patients Suffering Lipodystropy (LD) (Authored by L. Ruiz, E. Negredo, P. Domingo, A. Bonjoch, R. Paredes, E. Francia, M. Balagué, J. Romeu, A. Arnó, C.R. Fumaz, S. Johnston, G. Sirera, C. Tural, And B. Clotet for the LD Study Group. "irsi Caixa" Fndn. Hosp. Germans Trias i Pujol, and Hosp. S. Pau., Barcelona, Spain)
  Click here to view the original abstract

Since the original description of lipodystrophy and its association with protease inhibitors, there has been interest in switching off protease inhibitors to "protease-sparing" regimens in order to reverse the changes associated with this syndrome. A number of trials, mostly from Europe, have looked at this treatment switch.

One of the first of these is from Lidia Ruiz from Barcelona, looking at patients who were clinically stable on d4T/3TC and a protease inhibitor; randomly switching to d4T/ddI and nevirapine or continuing on the original protease regimen. In oral session 206 Dr. Ruiz presented 48-week results on over 200 patients. Ten percent of patients in the NVP and six percent of patients in the protease group (not significantly different) had an increase in viral load: all of these had multiple previous treatment regimens with presumed underlying resistance. The group that switched to NVP had significant improvement in cholesterol and triglycerides, but improvement in anthropometric measurements of body changes. The NVP switch group also reported significant improvement in quality of life.

A similar approach was taken by Tebas et al. (poster 45) from St. Louis. They reported on forty patients who had undetectable viral loads on their initial protease-containing regimen. All patients in this trial had their protease inhibitor switched to NVP, although seven patients (17%) developed a severe rash and were switched to efavirenz. At 24 weeks all but one patient remained undetectable (however, the patient became undetectable again on return to a PI). At this point there was significant improvement in triglycerides and HDL cholesterol, although total cholesterol and LDL were unchanged. Some measures of insulin sensitivity improved, although others did not show a significant difference. The ratio of central to peripheral fat on DEXA scan in ten patients actually worsened slightly, although the significance in this small number of patients is uncertain.

A slightly different approach was taken in study CNA30017, reported in posters 47 and 51. In this European/Canadian/Australian trial, 211 patients on their first protease inhibitor and two NRTI regimen were randomized to either have the protease inhibitor switched to abacavir or to remain on the protease regimen. At 24 weeks less than three percent of the patients in either group had a viral rebound to a PCR >400. There was a decrease in cholesterol and triglycerides in the abacavir arm, as well as improvement in insulin sensitivity. A substudy in France evaluated physical manifestations of lipodystrophy. They found a significant improvement in central obesity in 50% of the patients in the abacavir group who had this manifestation, with no improvement in the protease group. Other manifestations of lipodystrophy showed no significant change.

These studies, as well as other smaller ones that have been previously reported, demonstrate that switching from a protease inhibitor to an NNRTI or abacavir is generally virologically safe. The metabolic abnormalities associated with lipodystrophy frequently improve with this switch (although another small trial from Moyle did not show improvement in lipids with a switch to efavirenz). Improvement in the lipodystrophy body changes is variable: fat accumulation frequently improves, although the fat loss components do not.