Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen

Margaret A Fischl, Ann C. Collier, A. Lisa Mukherjee, Judith E. Feinberg, Lisa M. Demeter, Pablo Tebas, Marina Giuliano, Marjorie Dehlinger, Kevin Garren, Barbara Brizz, Roland Bassett

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

OBJECTIVES: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens. METHODS: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for ≥ 18 months. Patients received lopinavir/ritonavir (LPV/r) 533 mg/133 mg twice daily + efavirenz (EFV) 600 mg once daily or EFV + two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA > 200 copies/ml) or discontinuation because of study drug-related toxicity. RESULTS: After 2.1 years of follow up, patients receiving LPV/r + EFV discontinued treatment at a greater rate than patients receiving EFV + NRTI (P < 0.001). Twenty one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV + NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P = 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P = 0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P = 0.088 and P = 0.063 respectively). CONCLUSIONS: Switching to EFV + NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r + EFV.

Original languageEnglish
Pages (from-to)325-333
Number of pages9
JournalAIDS
Volume21
Issue number3
DOIs
StatePublished - Jan 1 2007

Fingerprint

efavirenz
Lopinavir
Ritonavir
Reverse Transcriptase Inhibitors
Pharmaceutical Preparations
Drug-Related Side Effects and Adverse Reactions
Nucleosides

Keywords

  • Advanced HIV
  • Non-nucleoside reverse transcriptase inhibitor
  • Protease inhibitor
  • Simplification therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen. / Fischl, Margaret A; Collier, Ann C.; Mukherjee, A. Lisa; Feinberg, Judith E.; Demeter, Lisa M.; Tebas, Pablo; Giuliano, Marina; Dehlinger, Marjorie; Garren, Kevin; Brizz, Barbara; Bassett, Roland.

In: AIDS, Vol. 21, No. 3, 01.01.2007, p. 325-333.

Research output: Contribution to journalArticle

Fischl, MA, Collier, AC, Mukherjee, AL, Feinberg, JE, Demeter, LM, Tebas, P, Giuliano, M, Dehlinger, M, Garren, K, Brizz, B & Bassett, R 2007, 'Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen', AIDS, vol. 21, no. 3, pp. 325-333. https://doi.org/10.1097/QAD.0b013e328011ddfa
Fischl, Margaret A ; Collier, Ann C. ; Mukherjee, A. Lisa ; Feinberg, Judith E. ; Demeter, Lisa M. ; Tebas, Pablo ; Giuliano, Marina ; Dehlinger, Marjorie ; Garren, Kevin ; Brizz, Barbara ; Bassett, Roland. / Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen. In: AIDS. 2007 ; Vol. 21, No. 3. pp. 325-333.
@article{60b96576d404443e9141658f4207e1a3,
title = "Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen",
abstract = "OBJECTIVES: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens. METHODS: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for ≥ 18 months. Patients received lopinavir/ritonavir (LPV/r) 533 mg/133 mg twice daily + efavirenz (EFV) 600 mg once daily or EFV + two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA > 200 copies/ml) or discontinuation because of study drug-related toxicity. RESULTS: After 2.1 years of follow up, patients receiving LPV/r + EFV discontinued treatment at a greater rate than patients receiving EFV + NRTI (P < 0.001). Twenty one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV + NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P = 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P = 0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P = 0.088 and P = 0.063 respectively). CONCLUSIONS: Switching to EFV + NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r + EFV.",
keywords = "Advanced HIV, Non-nucleoside reverse transcriptase inhibitor, Protease inhibitor, Simplification therapy",
author = "Fischl, {Margaret A} and Collier, {Ann C.} and Mukherjee, {A. Lisa} and Feinberg, {Judith E.} and Demeter, {Lisa M.} and Pablo Tebas and Marina Giuliano and Marjorie Dehlinger and Kevin Garren and Barbara Brizz and Roland Bassett",
year = "2007",
month = "1",
day = "1",
doi = "10.1097/QAD.0b013e328011ddfa",
language = "English",
volume = "21",
pages = "325--333",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen

AU - Fischl, Margaret A

AU - Collier, Ann C.

AU - Mukherjee, A. Lisa

AU - Feinberg, Judith E.

AU - Demeter, Lisa M.

AU - Tebas, Pablo

AU - Giuliano, Marina

AU - Dehlinger, Marjorie

AU - Garren, Kevin

AU - Brizz, Barbara

AU - Bassett, Roland

PY - 2007/1/1

Y1 - 2007/1/1

N2 - OBJECTIVES: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens. METHODS: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for ≥ 18 months. Patients received lopinavir/ritonavir (LPV/r) 533 mg/133 mg twice daily + efavirenz (EFV) 600 mg once daily or EFV + two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA > 200 copies/ml) or discontinuation because of study drug-related toxicity. RESULTS: After 2.1 years of follow up, patients receiving LPV/r + EFV discontinued treatment at a greater rate than patients receiving EFV + NRTI (P < 0.001). Twenty one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV + NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P = 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P = 0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P = 0.088 and P = 0.063 respectively). CONCLUSIONS: Switching to EFV + NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r + EFV.

AB - OBJECTIVES: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens. METHODS: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for ≥ 18 months. Patients received lopinavir/ritonavir (LPV/r) 533 mg/133 mg twice daily + efavirenz (EFV) 600 mg once daily or EFV + two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA > 200 copies/ml) or discontinuation because of study drug-related toxicity. RESULTS: After 2.1 years of follow up, patients receiving LPV/r + EFV discontinued treatment at a greater rate than patients receiving EFV + NRTI (P < 0.001). Twenty one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV + NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P = 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P = 0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P = 0.088 and P = 0.063 respectively). CONCLUSIONS: Switching to EFV + NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r + EFV.

KW - Advanced HIV

KW - Non-nucleoside reverse transcriptase inhibitor

KW - Protease inhibitor

KW - Simplification therapy

UR - http://www.scopus.com/inward/record.url?scp=33846596702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846596702&partnerID=8YFLogxK

U2 - 10.1097/QAD.0b013e328011ddfa

DO - 10.1097/QAD.0b013e328011ddfa

M3 - Article

C2 - 17255739

AN - SCOPUS:33846596702

VL - 21

SP - 325

EP - 333

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 3

ER -