Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-Week analysis from the RESIST-1 trial

Joseph Gathe, David A. Cooper, Charles Farthing, Dushyantha T Jayaweera, Dorece Norris, Gerald Pierone, Corklin R. Steinhart, Benoit Trottier, Sharon L. Walmsley, Cassy Workman, Geoffrey Mukwaya, Veronika Kohlbrenner, Catherine Dohnanyi, Scott McCallister, Douglas Mayers

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Abstract

Background. Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV- 1-infected patients. Methods. Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of ≥1 log10 less than the baseline level without treatment change at week 24. Results. Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a ≥1-log10 reduction in the HIV-1 load (intent-to-treat population; P < .0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. Conclusions. TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.

Original languageEnglish
Pages (from-to)1337-1346
Number of pages10
JournalClinical Infectious Diseases
Volume43
Issue number10
DOIs
StatePublished - Nov 15 2006

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Ritonavir
Protease Inhibitors
HIV-1
Therapeutics
Research Personnel
CD4 Lymphocyte Count
Antiviral Agents
tipranavir
Virus Diseases
Random Allocation
Aspartate Aminotransferases
North America
Alanine Transaminase
Nausea
Vomiting
Diarrhea
Triglycerides
Cholesterol
Safety

ASJC Scopus subject areas

  • Immunology

Cite this

Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients : 24-Week analysis from the RESIST-1 trial. / Gathe, Joseph; Cooper, David A.; Farthing, Charles; Jayaweera, Dushyantha T; Norris, Dorece; Pierone, Gerald; Steinhart, Corklin R.; Trottier, Benoit; Walmsley, Sharon L.; Workman, Cassy; Mukwaya, Geoffrey; Kohlbrenner, Veronika; Dohnanyi, Catherine; McCallister, Scott; Mayers, Douglas.

In: Clinical Infectious Diseases, Vol. 43, No. 10, 15.11.2006, p. 1337-1346.

Research output: Contribution to journalArticle

Gathe, J, Cooper, DA, Farthing, C, Jayaweera, DT, Norris, D, Pierone, G, Steinhart, CR, Trottier, B, Walmsley, SL, Workman, C, Mukwaya, G, Kohlbrenner, V, Dohnanyi, C, McCallister, S & Mayers, D 2006, 'Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-Week analysis from the RESIST-1 trial', Clinical Infectious Diseases, vol. 43, no. 10, pp. 1337-1346. https://doi.org/10.1086/508353
Gathe, Joseph ; Cooper, David A. ; Farthing, Charles ; Jayaweera, Dushyantha T ; Norris, Dorece ; Pierone, Gerald ; Steinhart, Corklin R. ; Trottier, Benoit ; Walmsley, Sharon L. ; Workman, Cassy ; Mukwaya, Geoffrey ; Kohlbrenner, Veronika ; Dohnanyi, Catherine ; McCallister, Scott ; Mayers, Douglas. / Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients : 24-Week analysis from the RESIST-1 trial. In: Clinical Infectious Diseases. 2006 ; Vol. 43, No. 10. pp. 1337-1346.
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abstract = "Background. Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV- 1-infected patients. Methods. Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of ≥1 log10 less than the baseline level without treatment change at week 24. Results. Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5{\%} of patients in the TPV/r arm and 22.3{\%} in the CPI/r arm had a ≥1-log10 reduction in the HIV-1 load (intent-to-treat population; P < .0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. Conclusions. TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.",
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T2 - 24-Week analysis from the RESIST-1 trial

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AU - Cooper, David A.

AU - Farthing, Charles

AU - Jayaweera, Dushyantha T

AU - Norris, Dorece

AU - Pierone, Gerald

AU - Steinhart, Corklin R.

AU - Trottier, Benoit

AU - Walmsley, Sharon L.

AU - Workman, Cassy

AU - Mukwaya, Geoffrey

AU - Kohlbrenner, Veronika

AU - Dohnanyi, Catherine

AU - McCallister, Scott

AU - Mayers, Douglas

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N2 - Background. Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV- 1-infected patients. Methods. Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of ≥1 log10 less than the baseline level without treatment change at week 24. Results. Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a ≥1-log10 reduction in the HIV-1 load (intent-to-treat population; P < .0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. Conclusions. TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.

AB - Background. Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV- 1-infected patients. Methods. Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of ≥1 log10 less than the baseline level without treatment change at week 24. Results. Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a ≥1-log10 reduction in the HIV-1 load (intent-to-treat population; P < .0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. Conclusions. TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.

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