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The Body PRO Covers: The 10th Conference on Retroviruses and Opportunistic Infections

Resistance Patterns of Nelfinavir vs. Lopinavir/r

February 11, 2003

  • Comparative Incidence and Temporal Accumulation of PI and NRTI Resistance in HIV-Infected Subjects Receiving Lopinavir/Ritonavir or Nelfinavir as Initial Therapy (Poster 600)
    Authored by D. Kempf, M. King, E. Bauer, J. Moseley, B. Bernstein, S. Brun, E. Sun
    View the original abstract


In a prospective, randomized clinical trial, lopinavir/r (LPV+RTV, Kaletra, or LPV/r) was found to have greater virologic efficacy than nelfinavir (NFV, Viracept), both combined with d4T (stavudine, Zerit) and 3TC (lamivudine, Epivir). This important clinical trial was published in 2002 in the New England Journal of Medicine (Walmsley, et al.). An interesting observation during that study was that patients experiencing virologic rebound on NFV were more likely to harbor resistance mutations than those on LPV/r. This poster presentation presents further data from that study that expand on this original finding.

Samples for genotype testing were obtained at weeks 24, 48, and 60 for all subjects with HIV RNA greater than 400 copies/mL. Resistance was defined as follows: for NFV, emergence of D30N or L90M; for LPV/r, any of a series of primary or active site mutations; for d4T, thymidine associated mutations; and for 3TC, the signature M184V mutation.

Results were as follows (% with resistance):


 NFVLPV/r
3TC Resistance29%7%
PI and 3TC Resistance20%0%
d4T and 3TC Resistance5%0%


As noted before, no primary protease inhibitor (PI) resistance mutations developed in the LPV/r group. Kaplan-Meier analyses showed that the time to develop 3TC resistance was significantly shorter among NFV-treated subjects than LPV/r-treated subjects (p<0.002).

This careful analysis adds to a body of data demonstrating the low likelihood of developing resistance using PIs (such as LPV/r) that have both a high genetic barrier to resistance and achieve good plasma concentrations. Although a potential argument could be made regarding the "salvage" potential of NFV resistance, it is clear that this comes at a cost of accumulating resistance mutations to other agents in the drug regimen (here d4T and 3TC). In addition, a significant minority of patients who develop NFV resistance will do so via the less favorable L90M pathway, which confers broader PI resistance.


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This article was provided by TheBodyPRO.com. It is a part of the publication The 10th Conference on Retroviruses and Opportunistic Infections.
 



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