Now Live: Breaking Research From XVII International AIDS Conference >>

Coverage provided by Alvan Fisher, M.D.

July 10, 2001

• Prevalence of Phenotypic Resistance to Amprenavir in Protease-Inhibitor-Experienced Patients: Data from CNAB3008 (Poster 608)
  Authored by Bruno, R.; Sacchi, P.; Panebianco, R.; Gatti, A.; Filice, G.; IRCCS S. Matteo Hospital Pavia, Italy; University of Pavia, Italy, Pavia, Italy

Resistance to antiretroviral drugs is extremely common and a major problem in treatment. Though we now have fifteen different antiretroviral agents available, the actual choices are limited by the known patterns of cross-resistance. We need more options for people carrying resistant and multi-resistant viruses. Amprenavir is a protease inhibitor with a distinctive resistance pattern and, in prior studies, has been shown to be less vulnerable to cross-resistance than other protease inhibitors. Abacavir is a nucleoside that remains effective in the presence of several nucleoside mutations. Both of these antiretrovirals may be especially useful in salvage settings (i.e., treatment after treatment failure).

This study collected phenotypic resistance data on 306 HIV-positive adults in Italy who enrolled in expanded access program for abacavir. All of these individuals were experiencing treatment failure as defined as failure to respond or tolerate standard antiretroviral regimens. The resistance tests were the Virco antivirogram assay of phenotypic resistance. The authors reported the results of the resistance assays for abacavir and amprenavir. At this time (March to December 1999) neither abacavir nor amprenavir were approved for use in Italy.

Seventy three percent of 281 samples showed full susceptibility (<4 fold reduced susceptibility) to abacavir while only 6% (>10 fold reduced susceptibility) were definitely resistant. Twenty one percent of the samples were in the intermediate (between 4 and 10 fold) range.

The data for amprenavir was also favorable. Of those samples that showed resistance to at least one protease inhibitor, 61% were fully susceptible to amprenavir, 6% were definitely resistant, and 33% showed intermediate resistance. Even more interesting was the data on those samples that showed resistance to four protease inhibitors (IDV, SQV, RTV and NFV). Of these isolates 52% were susceptible to amprenavir, 10% resistant and 38% intermediate. 30% of these isolates were susceptible to saquinavir, but less than 10% were susceptible to RTV, NFV or IDV.

The authors conclude that this study confirmed the uniqueness of amprenavir in terms of resistance. Susceptibility to amprenavir was maintained in the face of resistance to either one or all of the then available protease inhibitors. This study adds to several prior published studies that have confirmed the relatively low level of cross-resistance to amprenavir after prior exposure (and virologic failure) to other protease inhibitors. We still have limited clinical data indicating virologic response in individuals switched to amprenavir-containing regimens after virologic or treatment failure, but certainly this study (and the others) supports such use of amprenavir.

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