2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-15 September 2000, Toronto, Canada

LESSONS LEARNED FROM SWITCHING ANTIRETROVIRALS

Antiviral Therapy 2000; 5(Suppl. 5):17 (abstract no. O27)

WG Powderly
Washington University School of Medicine, St. Louis,Mo., USA

One approach to the emergence of long-term metabolic toxicity has been to try and substitute (or 'switch') one component of an antiretroviral regimen with an alternative potent drug, usually from a different class of antiretrovirals. The most common class of drug to be substituted has been the protease inhibitors. More recently, with the recognition that nucleoside reverse transcriptase inhibitors (NRTIs), may contribute to metabolic side-effects, studies switching NRTI components have been reported. Most of the studies that have been reported to date are uncontrolled and relatively brief in duration. Thus, any conclusions that are made must be by definition preliminary. However, certain trends are apparent. The first is that, in the vast majority of patients, switching appears to be virologically safe, i.e. if the patient has had sustained suppression of viral replication on the original regimen, this is usually maintained after the switch. The second trend is that some, but not all, metabolic disturbances appear to be reversible. Switching from a protease inhibitor to a non-nucleoside reverse transcriptase inhibitor (NNRTI) or to a third NRTI (usually abacavir) generally lowers triglyceride levels and decreases insulin resistance. Effects on cholesterol are more variable. However, there are inconsistencies in the effect seen across studies (especially if efavirenz is the NNRTI used). Substitution of the protease inhibitor has not been associated with reversal or improvement in fat redistribution. One small study substituting an alternative NRTI for stavudine reported improvement in lipoatrophy in a number of patients. Reversibility of bone disease has not yet been reported. Switch studies have the potential to provide important insight into the pathogenesis of the metabolic syndromes. However, there is a need for larger, controlled studies and a more standardized approach to definition of metabolic abnormalities.

000913
O27

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