ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-Week results

Robert L. Murphy, Scott Brun, Charles Hicks, Joseph J. Eron, Roy Gulick, Martin King, A. Clinton White, Constance Benson, Melanie Thompson, Harold A. Kessler, Scott Hammer, Richard Bertz, Ann Hsu, Anthony Japour, Eugene Sun

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

Objective: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. Design: Prospective, randomized, double-blind, multicenter. Methods: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). Results: Mean baseline HIV-1 RNA was 4.9 log 10 copies/ml in both groups and CD4 cell count was 398 × 10 6/l and 310 × 10 6/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (< 50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC 50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. Conclusions: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.

Original languageEnglish (US)
JournalAIDS
Volume15
Issue number1
DOIs
StatePublished - Jan 5 2001
Externally publishedYes

Fingerprint

Lopinavir
Stavudine
Ritonavir
Lamivudine
HIV Infections
HIV-1
RNA
Therapeutics
HIV Protease Inhibitors
CD4 Lymphocyte Count
Protease Inhibitors
Nausea
Antiviral Agents
Diarrhea
Safety

Keywords

  • ABT-378
  • ABT-378/r
  • Antiretroviral-naive
  • Phase II clinical study
  • Protease inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection : 48-Week results. / Murphy, Robert L.; Brun, Scott; Hicks, Charles; Eron, Joseph J.; Gulick, Roy; King, Martin; White, A. Clinton; Benson, Constance; Thompson, Melanie; Kessler, Harold A.; Hammer, Scott; Bertz, Richard; Hsu, Ann; Japour, Anthony; Sun, Eugene.

In: AIDS, Vol. 15, No. 1, 05.01.2001.

Research output: Contribution to journalArticle

Murphy, RL, Brun, S, Hicks, C, Eron, JJ, Gulick, R, King, M, White, AC, Benson, C, Thompson, M, Kessler, HA, Hammer, S, Bertz, R, Hsu, A, Japour, A & Sun, E 2001, 'ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-Week results', AIDS, vol. 15, no. 1. https://doi.org/10.1097/00002030-200101050-00002
Murphy, Robert L. ; Brun, Scott ; Hicks, Charles ; Eron, Joseph J. ; Gulick, Roy ; King, Martin ; White, A. Clinton ; Benson, Constance ; Thompson, Melanie ; Kessler, Harold A. ; Hammer, Scott ; Bertz, Richard ; Hsu, Ann ; Japour, Anthony ; Sun, Eugene. / ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection : 48-Week results. In: AIDS. 2001 ; Vol. 15, No. 1.
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abstract = "Objective: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. Design: Prospective, randomized, double-blind, multicenter. Methods: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). Results: Mean baseline HIV-1 RNA was 4.9 log 10 copies/ml in both groups and CD4 cell count was 398 × 10 6/l and 310 × 10 6/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91{\%} (< 50 copies/ml, 75{\%}) and 82{\%} (< 50 copies/ml, 79{\%}) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC 50 (effective concentration to inhibit 50{\%}) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. Conclusions: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.",
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T1 - ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection

T2 - 48-Week results

AU - Murphy, Robert L.

AU - Brun, Scott

AU - Hicks, Charles

AU - Eron, Joseph J.

AU - Gulick, Roy

AU - King, Martin

AU - White, A. Clinton

AU - Benson, Constance

AU - Thompson, Melanie

AU - Kessler, Harold A.

AU - Hammer, Scott

AU - Bertz, Richard

AU - Hsu, Ann

AU - Japour, Anthony

AU - Sun, Eugene

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N2 - Objective: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. Design: Prospective, randomized, double-blind, multicenter. Methods: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). Results: Mean baseline HIV-1 RNA was 4.9 log 10 copies/ml in both groups and CD4 cell count was 398 × 10 6/l and 310 × 10 6/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (< 50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC 50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. Conclusions: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.

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KW - ABT-378

KW - ABT-378/r

KW - Antiretroviral-naive

KW - Phase II clinical study

KW - Protease inhibitor

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