Clinical Validation and Applicability of Different Tipranavir/Ritonavir Genotypic Scores in HIV-1 Protease Inhibitor-Experienced Patients

被引:1
|
作者
Saracino, Annalisa [1 ]
Monno, Laura [2 ]
Tartaglia, Alessandra [1 ]
Tinelli, Carmine [3 ]
Seminari, Elena [3 ]
Maggiolo, Franco [4 ]
Bonora, Stefano [5 ,6 ]
Rusconi, Stefano
Micheli, Valeria [7 ]
Lo Caputo, Sergio [1 ,8 ]
Lazzaroni, Laura [9 ]
Ferrara, Sergio
Ladisa, Nicoletta [2 ]
Nasta, Paola [10 ]
Parruti, Giustino [11 ]
Bellagamba, Rita [12 ]
Forbici, Federica [12 ]
Angarano, Gioacchino [1 ]
机构
[1] Univ Foggia, Clin Infect Dis, I-71100 Foggia, Italy
[2] Univ Bari, Clin Infect Dis, I-70121 Bari, Italy
[3] Fdn IRCCS S Matteo, Clin Epidemiol & Biometr Unit, Pavia, Italy
[4] Osped Riuniti Bergamo, Div Infect Dis, I-24100 Bergamo, Italy
[5] Univ Turin, Dept Infect Dis, I-10124 Turin, Italy
[6] Univ Milan, Inst Infect & Trop Dis, L Sacco Hosp, I-20122 Milan, Italy
[7] L Sacco Hosp Vialba, Div Infect Dis 2, Milan, Italy
[8] SM Annunziata Hosp, Div Infect Dis, Florence, Italy
[9] Univ Insubria, Dept Infect Dis, Varese, Italy
[10] Univ Brescia, Inst Infect & Trop Dis, I-25121 Brescia, Italy
[11] Osped Civile Spirito Santo, Infect Dis Unit, Pescara, Italy
[12] IRCCS Lazzaro Spallanzani, Natl Inst Infect Dis, Rome, Italy
关键词
Antiretrovirals; protease inhibitors; genotypic resistance; tipranavir; REDUCED SUSCEPTIBILITY; INFECTED PATIENTS; RESISTANCE; RITONAVIR; EFFICACY; PHENOTYPE; FAILURE; TRIAL;
D O I
10.2174/157016209788680525
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 <= 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-naive 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.
引用
收藏
页码:425 / 433
页数:9
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