Clinical validation and applicability of different tipranavir/ritonavir genotypic scores in HIV-1 protease inhibitor-experienced patients.

Abstract

Tipranavir, a non-peptidic protease inhibitor which shows in vitro efficacy against some HIV-1-resistant strains, can be used in salvage therapies for multi-experienced HIV patients due to its peculiar resistance profile including 21 mutations at 16 protease positions according to International AIDS Society (IAS). Other genotypic scores, however, which attribute a different weight to single amino-acid substitutions, have been recently proposed. To validate the clinical utility of four different genotypic scores for selecting tipranavir responders, the baseline resistance pattern of 176 HIV heavily experienced patients was correlated with virological success (HIV-RNA<50 copies/ml) after 24 weeks of a new treatment based on tipranavir/ritonavir. Virological suppression after 24 weeks was reached by 42.5% of patients. With univariate analysis, genotypic scores were all associated with outcome but showed a low accuracy with ROC analysis, with the weighted score (WS) by Scherer et al. demonstrating the best performance with an AUC of 68%. Only 52% of patients classified as susceptible (WS< or =3) responded to the new therapy. The following variables were significantly associated (p<0.05) to failure with multivariate analysis: WS, log peak of HIV-RNA, IAS mutations: L33F, I54AMV, Q58E, and non-IAS mutation: N37DES. On the contrary, the use of T20 in T20-naïve patients and the V82AFSI and F53LY non-IAS mutations were associated with virological success. The study suggests that even if the "weighted" scores are able to interpret correctly the antiretroviral resistance profile of multi-experienced patients, it is difficult to individuate a cut-off which can be easily applied to this population for discriminating responders.

• Authors: Annalisa Saracino, Laura Monno, Alessandra Tartaglia, Carmine Tinelli, Elena Seminari, Franco Maggiolo, Stefano Bonora, Stefano Rusconi, Valeria Micheli, Sergio Lo Caputo, Laura Lazzaroni, Sergio Ferrara, Nicoletta Ladisa, Paola Nasta, Giustino Parruti, Rita Bellagamba, Federica Forbici, Gioacchino Angarano
• Journal: Current HIV research (Curr HIV Res) Vol. 7 Issue 4 Pg. 425-33 (Jul 2009) ISSN: 1873-4251 [Electronic] Netherlands
• PMID: 19601778 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Pyridines
• Pyrones
• RNA, Viral
• Sulfonamides
• HIV Protease
• p16 protease, Human immunodeficiency virus 1
• Ritonavir
• tipranavir

Topics

• Adult
• Amino Acid Substitution (genetics)
• Anti-HIV Agents (pharmacology)
• Antiretroviral Therapy, Highly Active (methods)
• Drug Resistance, Viral
• Female
• Genotype
• HIV Infections (drug therapy, virology)
• HIV Protease (genetics)
• HIV-1 (drug effects, genetics)
• Humans
• Male
• Middle Aged
• Mutation, Missense
• Pyridines (pharmacology)
• Pyrones (pharmacology)
• RNA, Viral (blood)
• Research Design
• Ritonavir (pharmacology)
• Sulfonamides
• Treatment Outcome
• Viral Load