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The Body PRO Covers: The 39th Annual Meeting of the Infectious Diseases Society of America

HIV/AIDS: Antiretroviral Therapy (Poster Session 87)

October 27, 2001

  • Efficacy of Lopinavir (LPV) in Heavily Pretreated Patients (Poster 675)
    Authored by O. Falusi, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL; K.Y. Smith, D. Huang, S. Badri, E. Narkiewicz, D. Merten, H. Kessler, B. Sha, Rush Medical College, Chicago, IL


Lopinavir is probably the most potent of the current protease inhibitors. In this study, Kessler's group in Chicago looked at the efficacy of lopinavir in heavily pretreated patients and tried to correlate the activity of this drug with the genotype and phenotype of the isolates prior to the initiation of a combination regimen that included lopinavir.

The 23 patients enrolled in this study had a lot of antiretroviral experience with all classes of drugs. The median number of protease inhibitor mutation was 6. Half of the patients had evidence of TAMs (thymidin analog associated mutations, which basically decrease the response to any nucleosides). So it was a very difficult population to treat. The results, in agreement with other studies already presented on lopinavir, were relatively good.

The most common selected combination was d4T, ddI and kaletra -- a common feature of studies that use phenotypic testing because the "cut offs" for "sensitive" and "resistant" are not clearly defined for these two nucleosides, and it is more difficult to detect resistance to d4T and ddI in vitro (unfortunately resistance happens in vivo, and, in the case of d4T, is associated with the presence of TAMs).

In this study, a significant proportion of patients obtained a virologic benefit (significant decrease of viral load) and an immunologic benefit (increase in CD4 cell count) with this combination.

Because of good residual activity in cases like the ones presented in this study, lopinavir is used more frequently as a "rescue" regimen and not as first-line therapy. Abbott is not very happy about that and would prefer to see it used more frequently as first-line therapy. However, clinicians have resisted that approach so far. The main problem with lopinavir (which in general is well-tolerated) is the elevations in cholesterol and triglycerides.

This study is too small to firmly conclude much, but complements the larger prospective trial done by Abbott (M97-765) for patients with evidence of virologic failure. In that study, lopinavir/ritonavir therapy was given to 70 patients who had failed a single PI-containing regimen. Patients were naive to NNRTIs (so the population is slightly different from the Kessler study). An NNRTI and at least one nucleoside were added at week three. At week 48, by intent-to-treat analysis, 70% had viral loads <400 copies/mL -- the best results so far in any "rescue" study.

We need more drugs for the "rescue" of patients with multi-drug resistance. The new protease inhibitors Tibotec 114 and tipranavir will be the first to be tested for this specific indication. New classes of drugs such as fusion inhibitors, with T-20 as the most representative drug, are already in phase III trials. Results will probably be available next year.


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This article was provided by TheBodyPRO.com. It is a part of the publication 39th Annual Meeting of the Infectious Diseases Society of America.
 



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