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 H. 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; 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

doi:10.1310/hct0902-91

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 H. 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 ReidTrevor 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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 <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm³ 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 language	English (US)
Pages (from-to)	91-102
Number of pages	12
Journal	HIV Clinical Trials
Volume	9
Issue number	2
DOIs	https://doi.org/10.1310/hct0902-91
State	Published - Mar 2008

Keywords

Antiretroviral therapy
Fosamprenavir
Lopinavir
Protease inhibitors
Ritonavir

ASJC Scopus subject areas

Pharmacology (medical)
Infectious Diseases

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Collier, A. C., Tierney, C., Downey, G. F., Eshleman, S. H., Kashuba, A., Klingman, K., Vergis, E. N., Pakes, G. E., Rooney, J. F., Rinehart, A., Mellors, J. W., Bishopric, G., Brizz, B., Cooper, M., Gideon, L., Grosskopf, N., Ha, B., Jarocki, B., Martinez, A., ... Garmon, D. (2008). Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. HIV Clinical Trials, 9(2), 91-102. https://doi.org/10.1310/hct0902-91

Collier, AC, Tierney, C, Downey, GF, Eshleman, SH, 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

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

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 <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm3 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.",

keywords = "Antiretroviral therapy, Fosamprenavir, Lopinavir, Protease inhibitors, Ritonavir",

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

year = "2008",

month = mar,

doi = "10.1310/hct0902-91",

language = "English (US)",

volume = "9",

pages = "91--102",

journal = "HIV Clinical Trials",

issn = "1528-4336",

publisher = "Taylor and Francis Ltd.",

number = "2",

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TY - JOUR

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 H.

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 <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm3 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 <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm3 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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U2 - 10.1310/hct0902-91

DO - 10.1310/hct0902-91

M3 - Article

C2 - 18474494

AN - SCOPUS:44949247362

SN - 1528-4336

VL - 9

SP - 91

EP - 102

JO - HIV Clinical Trials

JF - HIV Clinical Trials

IS - 2

ER -

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

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ASJC Scopus subject areas

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