"Viral Fitness Data Point To Nelfinavir As Best Initial PI
(AIDS Therapies)"
<<It's not what happens when it works, but what happens when it stops working that may make nelfinavir the best protease inhibitor for
first-line use.>>
<<New in vitro studies show that HIV resistant to nelfinavir is
weaker than virus resistant to other HIV protease inhibitors
(PIs). They may explain clinical observations that patients
failing first-line highly active antiretroviral therapy (HAART)
regimens including nelfinavir are more likely than those failing
other regimens to respond well to salvage therapy.
"Hypotheses based on the greater fitness impairment of the
nelfinavir-selected D30N mutant are suggested to explain
observations that prolonged responses to delayed salvage
regimens, including alternate PIs, may be relatively common after
nelfinavir failure," suggested Javier Martinez-Picado and
colleagues of Harvard Medical School, Boston, Massachusetts.
<Martinez-Picado et al. reported their findings in the Journal of
Virology ("Replicative Fitness of Protease-Inhibitor-Resistant
Mutants of Human Immunodeficiency Virus Type 1," J Virol, May
1999;73(5):3744-52).
<The researchers tested the relative fitness of HIV mutants
selected by various PIs in a series of in vitro experiments,
including competitive co-culture.
<They found that the D30N mutation that confers resistance to
nelfinavir (Viracept, Agouron) substantially reduced ability of
the virus to replicate. They also found that the L90M mutation
that confers resistance to saquinavir (Fortovase, Roche)
moderately impairs viral fitness. Even when multiply substituted
(M46I/L63P/V82T/I84V or L10R/M46I/L63P/V82T/I84V), mutants
resistant to indinavir (Crixivan, Merck) were just as fit as
wild-type HIV.
_Daniel J. DeNoon, Senior Editor
AIDSWEEKLY Plus; Monday, May 10, 1999
aegis.com
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