• Management of PI-associated Metabolic Changes by Substitution with Efavirenz in Virologically Controlled HIV+ Persons
  Poster 1533
  Authored by F. Maggiolo, M. Migliorino, G. Pravettoni, M. Rizzi, S. Caprioli, F. Suter
• Maintenance Therapy with Non-Nucleoside Reverse Transcriptase Inhibitors for HIV-Infected Patients with Intolerance to a Successful Protease Inhibitor-Containing Regimen (BEGIN Study): Efficacy and Resistance Data
  Poster 1537
  Authored by J. L. Casado, J. Arrizabalaga, A. Moreno, J. A. Iribarren, V. Muñoz, A. Antela, F. Dronda, M. J. Perez-Elias, S. Moreno

Switching antiretroviral agents after successful viral load suppression has become a popular practice. Some of the reasons for "switching" include simplification of pill burden, decreased unpleasant side effects, management of drug-related toxicity and an attempt to revert some of the metabolic abnormalities associated with the use of these drugs. Simplification strategies that merely discontinue the use of one or two drugs of an initial successful regimen have produced mixed results. More studies now have documented the successful maintenance in suppression of viral load after "switching" to a regimen of equal potency. Several studies presented today looked at the implication of some of those switches in terms of efficacy, tolerability, and sustained virological responses.

Management of PI-associated Metabolic Changes by Substitution with Efavirenz in Virologically Controlled HIV+ Persons (Poster 1533)

This study, from Italy by Maggiolo et al., was conducted to evaluate the possibility that "switching" a protease inhibitor (PI) for efavirenz will reduce the PI-associated metabolic alterations. Fifty patients on a stable PI-containing ART regimen and with suppressed viral load (<500 copies/ml) were enrolled. Results after four weeks of switching showed a marked decrease in triglycerides. No increase in cholesterol was noted after switching to efavirenz. These patients maintained suppression of their viral load and stable CD4 counts during the duration of the study. The author concluded that "switching" PI for efavirenz on patients with controlled infection statistically leads to reduction of triglycerides without compromising the immunological and virological response.

Several studies in the past have reported that it is fairly safe switching to a NNRTI from a PI, in terms of maintaining suppression of viral loads. One of those studies was DMP 266-049, presented at this meeting by Dr. A. Rachlis (#475). It is important, however, that the patients to be switched to a NNRTI from a PI, should be on their first ART regimen -- without past monotherapy exposure to NRTI -- specifically AZT and 3TC. There are some concerns that the presence of some NRTIs-associated mutations may diminish subsequent response to a NNRTI. More studies will be needed to assess the safety of this type of switching on patients previously exposed to others ART. Dr. Maggiolo did not specify if the patients in his study were indeed on their first regimen at the time they were switched.

Maintenance Therapy with Non-Nucleoside Reverse Transcriptase Inhibitors for HIV-Infected Patients with Intolerance to a Successful Protease Inhibitor-Containing Regimen (BEGIN Study): Efficacy and Resistance Data (Poster 1537)

This is a study from Spain, presented by Dr. Casado, to determine the efficacy and tolerance of nevirapine or efavirenz after switching from a PI-containing regimen. Patients in this study also were NNRTI-naive and with suppressed viral load below the limits of quantitation. The "switch" in this study was done mainly due to intolerance to the PIs (lipodystrophic changes, GI side effects, nephrolitiasis, increased lipids, diabetes and hepatitis). Dr. Casado also tried to assess the risk factors for failing the new NNRTI regimen.

103 patients were offered to switch their PI to an NNRTI after presenting with intolerance or toxicity related to their PI. Seventy patients were switched to nevirapine and 33 to efavirenz. At six months most patients remained with suppressed HIV viral loads. Of the patients who failed the new NNRTI, several risk factors were identified as factors associated for that failure -- including a longer period of previous NRTIs with poor adherence to it. A genotypic resistance analysis in those patients revealed the presence of mutations in codons 215, 184, 103, 106, and 181. Metabolic abnormalities mildly improved during the first six months of therapy. There were no significant changes in the lipodystrophic changes as self-reported by the patient.

In my opinion, the scope of this study was too wide in terms of using more than one NNRTI, enrolling patients with various NRTI experiences, assessing the significance of genotypic mutations, determining the risk factors for failure to the new NNRTI, assessing metabolic parameters and self-reported lipodystrophic changes. Nevertheless, this study supports what other previous studies have shown, in terms of safety of a switching to a NNRTI from a PI, on patients with little or no experience to NRTIs.