Ritonavir-Boosted Tipranavir Demonstrates Superior Efficacy to Ritonavir-Boosted Protease Inhibitors in Treatment-Experienced HIV-Infected Patients: 24-Week Results of the RESIST-2 Trial

Cahn, Pedro; Villacian, Jorge; Lazzarin, Adriano; Katlama, Christine; Grinsztejn, Beatriz; Arastéh, Keikawus; Patricia, López; Clumeck, Nathan; Gerstoft, Jan; Stavrianeas, N.; Moreno, Santiago; Antúnes, Francisco; Neubacher, Dietmar; Mayers, Douglas L.

doi:10.1086/508352

Cited by 82 publications

(75 citation statements)

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“…In our patients, in fact, OBS was an independent predictor of VR by both multivariate linear and logistic regression analyses. Moreover, subjects with two or more active drugs in the OB regimen were more likely to achieve a VR than those with less active drugs, confirming the possible OBS cutoff suggested previously (3,6,8).…”

Section: Discussionsupporting

confidence: 80%

“…In the RESIST-1 and the RESIST-2 studies, the efficacy and safety of TPV-RTV (500 mg/200 mg twice daily) in 1,509 highly treatment-experienced HIV-1-positive patients were assessed. Analysis at 48 weeks showed that the TPV-RTV-containing regimens significantly improved the immune and virological responses (VRs) compared to the responses to an RTV-boosted comparator PI plus an optimized background (OB) regimen (3,6,8).Different factors have been found to be associated with the virological and immunological responses: a lower viral load (VL) at the baseline, the use of enfuvirtide (T20) as a part of the OB regimen, the presence of two or more active drugs in the OB regimen (OB score [OBS], Ն2) (3,6,8), and the baseline numbers of specific TPV-associated resistance mutations (TPV RMs) (2). Moreover, the TPV trough concentration (C trough ) and phenotypic inhibitory quotient (IQ) have also been shown to be associated with the VR at week 24 (12a, 16).…”

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confidence: 99%

“…Different factors have been found to be associated with the virological and immunological responses: a lower viral load (VL) at the baseline, the use of enfuvirtide (T20) as a part of the OB regimen, the presence of two or more active drugs in the OB regimen (OB score [OBS], Ն2) (3,6,8), and the baseline numbers of specific TPV-associated resistance mutations (TPV RMs) (2). Moreover, the TPV trough concentration (C trough ) and phenotypic inhibitory quotient (IQ) have also been shown to be associated with the VR at week 24 (12a, 16).…”

mentioning

confidence: 99%

“…In vitro data have shown that resistance to TPV develops slowly (5). When TPV is coadministered with ritonavir (RTV) as a booster, TPV has been shown to have potent antiviral activity in multidrug-experienced patients (3,6,9,12). In the RESIST-1 and the RESIST-2 studies, the efficacy and safety of TPV-RTV (500 mg/200 mg twice daily) in 1,509 highly treatment-experienced HIV-1-positive patients were assessed.…”

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confidence: 99%

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confidence: 99%

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Tipranavir (TPV) Genotypic Inhibitory Quotient Predicts Virological Response at 48 Weeks to TPV-Based Salvage Regimens

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Calcagno

et al. 2008

Antimicrob Agents Chemother

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The virological response (VR) to a tipranavir-ritonavir (TPV-RTV)-based regimen had been shown to be associated with a number of mutations in the protease gene, the use of enfuvirtide (T20), and the TPV phenotypic inhibitory quotient (IQ). The role of the TPV genotypic IQ (gIQ) has not yet been fully investigated. The aim of our study was to evaluate the relationship between the TPV gIQ and the VR at 48 weeks to TPV-based salvage regimens. Patients placed on regimens containing two nucleoside reverse transcriptase inhibitors plus TPV-RTV 500/200 mg twice a day with or without T20 were prospectively studied. Regular follow-up was performed over the study period. VR, considered a viral load (VL) decrease of >1 log unit and/or the achievement of <50 copies/ml with no VL rebound of >0.5 log unit compared to the maximal VL decrease at week 48, was assessed. Thirty-eight patients who had received multiple drugs were included. At week 48 the VL decrease was ؊1.48 (interquartile range [IQR], ؊2.88 to ؊0.48), 15 patients (39.5%) had VLs of <50 copies/ml, and the CD4 ؉ cell count increase was 37 cells/mm 3 (IQR, ؊30 to ؉175). Twenty subjects (52.6%) achieved VRs. The TPV gIQ and optimized background score (OBS) were independently associated with higher VL decreases. The TPV gIQ and OBS were also independent predictors of a VR at week 48. TPV gIQ and OBS cutoff values of 14,500 and 2, respectively, were associated with a higher rate of VR. The TPV gIQ was shown to be able to predict the VR at 48 weeks to TPV-containing salvage regimens better than the TPV trough concentration or TPV-associated mutations alone. A possible TPV gIQ cutoff value of 14,500 for reaching a VR at week 48 was suggested. Further studies are needed in order to evaluate the calculation of TPV gIQ as a new tool for the optimization of TPV-based salvage therapy.Tipranavir (TPV) is a nonpeptidic protease inhibitor with potent in vitro activity against most human immunodeficiency virus (HIV) type 1 (HIV-1) strains resistant to other protease inhibitors (PIs) (1,14,15). In vitro data have shown that resistance to TPV develops slowly (5). When TPV is coadministered with ritonavir (RTV) as a booster, TPV has been shown to have potent antiviral activity in multidrug-experienced patients (3,6,9,12). In the RESIST-1 and the RESIST-2 studies, the efficacy and safety of TPV-RTV (500 mg/200 mg twice daily) in 1,509 highly treatment-experienced HIV-1-positive patients were assessed. Analysis at 48 weeks showed that the TPV-RTV-containing regimens significantly improved the immune and virological responses (VRs) compared to the responses to an RTV-boosted comparator PI plus an optimized background (OB) regimen (3,6,8).Different factors have been found to be associated with the virological and immunological responses: a lower viral load (VL) at the baseline, the use of enfuvirtide (T20) as a part of the OB regimen, the presence of two or more active drugs in the OB regimen (OB score [OBS], Ն2) (3,6,8), and the baseline numbers of specific TPV-associated resistance mu...

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Section: Discussionsupporting

confidence: 80%