Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV

Ann C. Collier, Camlin Tierney, Gerald F. Downey, Susan Eshleman, Angela Kashuba, Karin Klingman, Emanuel N. Vergis, Gary E. Pakes, James F. Rooney, Alex Rinehart, John W. Mellors, George Bishopric, Barbara Brizz, Marlene Cooper, Linda Gideon, Nicole Grosskopf, Belinda Ha, Bernadette Jarocki, Ana Martinez, Jane Reid & 32 others Trevor Scott, Nancy Tustin, Ed Acosta, Merissa L. Astley, Benigno Rodriguez, Patricia Walton, Judith Feinberg, Jenifer Baer, Luis M. Mendez, Frances Canchola, Michael F. Para, Laura Laughlin, Joseph J. Eron, Cheryl Marcus, Valery Hughes, Todd Stroberg, Brad Hare, Jody Lawrence, Daniel J. Skiest, Jesse Tarbutton, William A. O'Brien, Cheryl Mogridge, Karen Cavanagh, Charles Gonzalez, Hector H. Bolivar, Margaret A. Fischl, N. Jeanne Conley, Laura Olin, Mitchell Goldman, Beth Zwickl, Donna Mildvan, Donald Garmon

Research output: Contribution to journalArticle

Abstract

Purpose: To compare activity and safety of a regimen containing lopinavir/ritonavir (LPV/r) + fosamprenavir (FPV) to regimens with LPV/r or FPV + r and to test the hypothesis that a ritonavir-enhanced dual protease inhibitor (PI) regimen has better antiviral activity. Method: This study was a multicenter, open-label, randomized study. HIV-infected adults with prior PI failure were selectively randomized based on prior PI experience to either LPV/r, FPV + r, or LPV/r + FPV. All patients received tenofovir DF and 1 to 2 nucleoside reverse transcriptase inhibitors. Results: Baseline characteristics were similar across arms. Study enrollment and follow-up were stopped early (N = 56) because pharmacokinetic analyses showed significantly lower LPV and FPV exposures in the dual-PI arm. At Week 24, proportions achieving >1 log 10 decline in HIV RNA or 3 increases were 81 vs. 41 (ITT, p = .4) and 114 vs. 43 (AT, p = .08), respectively. Clinical events and toxicity rates were not different between arms. Conclusion: The trial was unable to show a difference between dual versus single PIs in ITT analyses but favored dual PIs in AT analyses.

Original languageEnglish (US)
Pages (from-to)91-102
Number of pages12
JournalHIV Clinical Trials
Volume9
Issue number2
DOIs
StatePublished - Mar 2008

Fingerprint

Ritonavir
Lopinavir
Protease Inhibitors
HIV
Tenofovir
Reverse Transcriptase Inhibitors
Nucleosides
Antiviral Agents
Pharmacokinetics
fosamprenavir
RNA
Safety

Keywords

  • Antiretroviral therapy
  • Fosamprenavir
  • Lopinavir
  • Protease inhibitors
  • Ritonavir

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. / Collier, Ann C.; Tierney, Camlin; Downey, Gerald F.; Eshleman, Susan; Kashuba, Angela; Klingman, Karin; Vergis, Emanuel N.; Pakes, Gary E.; Rooney, James F.; Rinehart, Alex; Mellors, John W.; Bishopric, George; Brizz, Barbara; Cooper, Marlene; Gideon, Linda; Grosskopf, Nicole; Ha, Belinda; Jarocki, Bernadette; Martinez, Ana; Reid, Jane; Scott, Trevor; Tustin, Nancy; Acosta, Ed; Astley, Merissa L.; Rodriguez, Benigno; Walton, Patricia; Feinberg, Judith; Baer, Jenifer; Mendez, Luis M.; Canchola, Frances; Para, Michael F.; Laughlin, Laura; Eron, Joseph J.; Marcus, Cheryl; Hughes, Valery; Stroberg, Todd; Hare, Brad; Lawrence, Jody; Skiest, Daniel J.; Tarbutton, Jesse; O'Brien, William A.; Mogridge, Cheryl; Cavanagh, Karen; Gonzalez, Charles; Bolivar, Hector H.; Fischl, Margaret A.; Conley, N. Jeanne; Olin, Laura; Goldman, Mitchell; Zwickl, Beth; Mildvan, Donna; Garmon, Donald.

In: HIV Clinical Trials, Vol. 9, No. 2, 03.2008, p. 91-102.

Research output: Contribution to journalArticle

Collier, AC, Tierney, C, Downey, GF, Eshleman, S, Kashuba, A, Klingman, K, Vergis, EN, Pakes, GE, Rooney, JF, Rinehart, A, Mellors, JW, Bishopric, G, Brizz, B, Cooper, M, Gideon, L, Grosskopf, N, Ha, B, Jarocki, B, Martinez, A, Reid, J, Scott, T, Tustin, N, Acosta, E, Astley, ML, Rodriguez, B, Walton, P, Feinberg, J, Baer, J, Mendez, LM, Canchola, F, Para, MF, Laughlin, L, Eron, JJ, Marcus, C, Hughes, V, Stroberg, T, Hare, B, Lawrence, J, Skiest, DJ, Tarbutton, J, O'Brien, WA, Mogridge, C, Cavanagh, K, Gonzalez, C, Bolivar, HH, Fischl, MA, Conley, NJ, Olin, L, Goldman, M, Zwickl, B, Mildvan, D & Garmon, D 2008, 'Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV', HIV Clinical Trials, vol. 9, no. 2, pp. 91-102. https://doi.org/10.1310/hct0902-91
Collier, Ann C. ; Tierney, Camlin ; Downey, Gerald F. ; Eshleman, Susan ; Kashuba, Angela ; Klingman, Karin ; Vergis, Emanuel N. ; Pakes, Gary E. ; Rooney, James F. ; Rinehart, Alex ; Mellors, John W. ; Bishopric, George ; Brizz, Barbara ; Cooper, Marlene ; Gideon, Linda ; Grosskopf, Nicole ; Ha, Belinda ; Jarocki, Bernadette ; Martinez, Ana ; Reid, Jane ; Scott, Trevor ; Tustin, Nancy ; Acosta, Ed ; Astley, Merissa L. ; Rodriguez, Benigno ; Walton, Patricia ; Feinberg, Judith ; Baer, Jenifer ; Mendez, Luis M. ; Canchola, Frances ; Para, Michael F. ; Laughlin, Laura ; Eron, Joseph J. ; Marcus, Cheryl ; Hughes, Valery ; Stroberg, Todd ; Hare, Brad ; Lawrence, Jody ; Skiest, Daniel J. ; Tarbutton, Jesse ; O'Brien, William A. ; Mogridge, Cheryl ; Cavanagh, Karen ; Gonzalez, Charles ; Bolivar, Hector H. ; Fischl, Margaret A. ; Conley, N. Jeanne ; Olin, Laura ; Goldman, Mitchell ; Zwickl, Beth ; Mildvan, Donna ; Garmon, Donald. / Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. In: HIV Clinical Trials. 2008 ; Vol. 9, No. 2. pp. 91-102.
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T1 - Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV

AU - Collier, Ann C.

AU - Tierney, Camlin

AU - Downey, Gerald F.

AU - Eshleman, Susan

AU - Kashuba, Angela

AU - Klingman, Karin

AU - Vergis, Emanuel N.

AU - Pakes, Gary E.

AU - Rooney, James F.

AU - Rinehart, Alex

AU - Mellors, John W.

AU - Bishopric, George

AU - Brizz, Barbara

AU - Cooper, Marlene

AU - Gideon, Linda

AU - Grosskopf, Nicole

AU - Ha, Belinda

AU - Jarocki, Bernadette

AU - Martinez, Ana

AU - Reid, Jane

AU - Scott, Trevor

AU - Tustin, Nancy

AU - Acosta, Ed

AU - Astley, Merissa L.

AU - Rodriguez, Benigno

AU - Walton, Patricia

AU - Feinberg, Judith

AU - Baer, Jenifer

AU - Mendez, Luis M.

AU - Canchola, Frances

AU - Para, Michael F.

AU - Laughlin, Laura

AU - Eron, Joseph J.

AU - Marcus, Cheryl

AU - Hughes, Valery

AU - Stroberg, Todd

AU - Hare, Brad

AU - Lawrence, Jody

AU - Skiest, Daniel J.

AU - Tarbutton, Jesse

AU - O'Brien, William A.

AU - Mogridge, Cheryl

AU - Cavanagh, Karen

AU - Gonzalez, Charles

AU - Bolivar, Hector H.

AU - Fischl, Margaret A.

AU - Conley, N. Jeanne

AU - Olin, Laura

AU - Goldman, Mitchell

AU - Zwickl, Beth

AU - Mildvan, Donna

AU - Garmon, Donald

PY - 2008/3

Y1 - 2008/3

N2 - Purpose: To compare activity and safety of a regimen containing lopinavir/ritonavir (LPV/r) + fosamprenavir (FPV) to regimens with LPV/r or FPV + r and to test the hypothesis that a ritonavir-enhanced dual protease inhibitor (PI) regimen has better antiviral activity. Method: This study was a multicenter, open-label, randomized study. HIV-infected adults with prior PI failure were selectively randomized based on prior PI experience to either LPV/r, FPV + r, or LPV/r + FPV. All patients received tenofovir DF and 1 to 2 nucleoside reverse transcriptase inhibitors. Results: Baseline characteristics were similar across arms. Study enrollment and follow-up were stopped early (N = 56) because pharmacokinetic analyses showed significantly lower LPV and FPV exposures in the dual-PI arm. At Week 24, proportions achieving >1 log 10 decline in HIV RNA or 3 increases were 81 vs. 41 (ITT, p = .4) and 114 vs. 43 (AT, p = .08), respectively. Clinical events and toxicity rates were not different between arms. Conclusion: The trial was unable to show a difference between dual versus single PIs in ITT analyses but favored dual PIs in AT analyses.

AB - Purpose: To compare activity and safety of a regimen containing lopinavir/ritonavir (LPV/r) + fosamprenavir (FPV) to regimens with LPV/r or FPV + r and to test the hypothesis that a ritonavir-enhanced dual protease inhibitor (PI) regimen has better antiviral activity. Method: This study was a multicenter, open-label, randomized study. HIV-infected adults with prior PI failure were selectively randomized based on prior PI experience to either LPV/r, FPV + r, or LPV/r + FPV. All patients received tenofovir DF and 1 to 2 nucleoside reverse transcriptase inhibitors. Results: Baseline characteristics were similar across arms. Study enrollment and follow-up were stopped early (N = 56) because pharmacokinetic analyses showed significantly lower LPV and FPV exposures in the dual-PI arm. At Week 24, proportions achieving >1 log 10 decline in HIV RNA or 3 increases were 81 vs. 41 (ITT, p = .4) and 114 vs. 43 (AT, p = .08), respectively. Clinical events and toxicity rates were not different between arms. Conclusion: The trial was unable to show a difference between dual versus single PIs in ITT analyses but favored dual PIs in AT analyses.

KW - Antiretroviral therapy

KW - Fosamprenavir

KW - Lopinavir

KW - Protease inhibitors

KW - Ritonavir

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