Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients

4 Year follow-up study

Charles Hicks, Martin S. King, Roy M. Gulick, A. Clinton White, Joseph J. Eron, Harold A. Kessler, Constance Benson, Kathryn R. King, Robert L. Murphy, Scott C. Brun

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Objective: Combination antiretroviral therapy with lopinavir/ritonavir (LPV/r) has been highly effective in clinical trials. Results of long-term therapy with LPV/r-based regimens have not been previously reported. This study describes the 4-year (204-week) safety and antiretroviral activity of LPV/r-based treatment in antiretroviral-naive individuals. Design: Long-term, open-label follow-up of a phase II, prospective, randomized, multicenter trial. Methods: A group of 100 antiretroviral-naive HIV-infected patients were randomized to one of three blinded doses of LPV/r [200/100 mg (n = 16), 400/100 mg (n = 51), or 400/200 mg (n = 33)] with stavudine 40 mg and lamivudine 150 mg every 12 hours. After 48 weeks, LPV/r was dosed open-label at 400/100 mg every 12 hours with stavudine and lamivudine. Results: Mean baseline plasma HIV-1 RNA and CD4 cell count were 4.9 log 10 copies/ ml and 338 × 10 6 cells/l, respectively. At week 204, 72 patients remained on study, 70 of whom had HIV-1 RNA < 50 copies/ml (70% by intent-to-treat analysis). Twenty-eight patients discontinued therapy prior to week 204 because of adverse events (n = 10), lost to follow-up (n = 9), or other reasons (n = 9). Of 15 patients who met protocol-defined criteria for virologic failure, seven remained on the study regimen and their HIV-1 RNA was re-suppressed to < 50 copies/ml at week 204. Genotypic analysis of rebound viral isolates was available from 10 patients, including all eight patients who discontinued the study prematurely. No isolate demonstrated primary or active site mutations in protease. The most common adverse events were gastrointestinal symptoms and lipid elevations. Conclusions: LPV/r-based therapy provides durable antiretroviral response and is generally well tolerated through 204 weeks of therapy.

Original languageEnglish (US)
Pages (from-to)775-779
Number of pages5
JournalAIDS
Volume18
Issue number5
DOIs
StatePublished - Mar 26 2004
Externally publishedYes

Fingerprint

Lopinavir
Ritonavir
Safety
Stavudine
HIV-1
Lamivudine
RNA
Therapeutics
Lost to Follow-Up
CD4 Lymphocyte Count
Multicenter Studies
Catalytic Domain
Peptide Hydrolases
Clinical Trials
HIV
Lipids
Mutation

Keywords

  • Antiretroviral activity
  • Cholesterol
  • Lopinavir
  • Ritonavir
  • Safety
  • Triglycerides
  • Virologic failure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients : 4 Year follow-up study. / Hicks, Charles; King, Martin S.; Gulick, Roy M.; White, A. Clinton; Eron, Joseph J.; Kessler, Harold A.; Benson, Constance; King, Kathryn R.; Murphy, Robert L.; Brun, Scott C.

In: AIDS, Vol. 18, No. 5, 26.03.2004, p. 775-779.

Research output: Contribution to journalArticle

Hicks, C, King, MS, Gulick, RM, White, AC, Eron, JJ, Kessler, HA, Benson, C, King, KR, Murphy, RL & Brun, SC 2004, 'Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 Year follow-up study', AIDS, vol. 18, no. 5, pp. 775-779. https://doi.org/10.1097/00002030-200403260-00008
Hicks, Charles ; King, Martin S. ; Gulick, Roy M. ; White, A. Clinton ; Eron, Joseph J. ; Kessler, Harold A. ; Benson, Constance ; King, Kathryn R. ; Murphy, Robert L. ; Brun, Scott C. / Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients : 4 Year follow-up study. In: AIDS. 2004 ; Vol. 18, No. 5. pp. 775-779.
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abstract = "Objective: Combination antiretroviral therapy with lopinavir/ritonavir (LPV/r) has been highly effective in clinical trials. Results of long-term therapy with LPV/r-based regimens have not been previously reported. This study describes the 4-year (204-week) safety and antiretroviral activity of LPV/r-based treatment in antiretroviral-naive individuals. Design: Long-term, open-label follow-up of a phase II, prospective, randomized, multicenter trial. Methods: A group of 100 antiretroviral-naive HIV-infected patients were randomized to one of three blinded doses of LPV/r [200/100 mg (n = 16), 400/100 mg (n = 51), or 400/200 mg (n = 33)] with stavudine 40 mg and lamivudine 150 mg every 12 hours. After 48 weeks, LPV/r was dosed open-label at 400/100 mg every 12 hours with stavudine and lamivudine. Results: Mean baseline plasma HIV-1 RNA and CD4 cell count were 4.9 log 10 copies/ ml and 338 × 10 6 cells/l, respectively. At week 204, 72 patients remained on study, 70 of whom had HIV-1 RNA < 50 copies/ml (70{\%} by intent-to-treat analysis). Twenty-eight patients discontinued therapy prior to week 204 because of adverse events (n = 10), lost to follow-up (n = 9), or other reasons (n = 9). Of 15 patients who met protocol-defined criteria for virologic failure, seven remained on the study regimen and their HIV-1 RNA was re-suppressed to < 50 copies/ml at week 204. Genotypic analysis of rebound viral isolates was available from 10 patients, including all eight patients who discontinued the study prematurely. No isolate demonstrated primary or active site mutations in protease. The most common adverse events were gastrointestinal symptoms and lipid elevations. Conclusions: LPV/r-based therapy provides durable antiretroviral response and is generally well tolerated through 204 weeks of therapy.",
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T1 - Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients

T2 - 4 Year follow-up study

AU - Hicks, Charles

AU - King, Martin S.

AU - Gulick, Roy M.

AU - White, A. Clinton

AU - Eron, Joseph J.

AU - Kessler, Harold A.

AU - Benson, Constance

AU - King, Kathryn R.

AU - Murphy, Robert L.

AU - Brun, Scott C.

PY - 2004/3/26

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N2 - Objective: Combination antiretroviral therapy with lopinavir/ritonavir (LPV/r) has been highly effective in clinical trials. Results of long-term therapy with LPV/r-based regimens have not been previously reported. This study describes the 4-year (204-week) safety and antiretroviral activity of LPV/r-based treatment in antiretroviral-naive individuals. Design: Long-term, open-label follow-up of a phase II, prospective, randomized, multicenter trial. Methods: A group of 100 antiretroviral-naive HIV-infected patients were randomized to one of three blinded doses of LPV/r [200/100 mg (n = 16), 400/100 mg (n = 51), or 400/200 mg (n = 33)] with stavudine 40 mg and lamivudine 150 mg every 12 hours. After 48 weeks, LPV/r was dosed open-label at 400/100 mg every 12 hours with stavudine and lamivudine. Results: Mean baseline plasma HIV-1 RNA and CD4 cell count were 4.9 log 10 copies/ ml and 338 × 10 6 cells/l, respectively. At week 204, 72 patients remained on study, 70 of whom had HIV-1 RNA < 50 copies/ml (70% by intent-to-treat analysis). Twenty-eight patients discontinued therapy prior to week 204 because of adverse events (n = 10), lost to follow-up (n = 9), or other reasons (n = 9). Of 15 patients who met protocol-defined criteria for virologic failure, seven remained on the study regimen and their HIV-1 RNA was re-suppressed to < 50 copies/ml at week 204. Genotypic analysis of rebound viral isolates was available from 10 patients, including all eight patients who discontinued the study prematurely. No isolate demonstrated primary or active site mutations in protease. The most common adverse events were gastrointestinal symptoms and lipid elevations. Conclusions: LPV/r-based therapy provides durable antiretroviral response and is generally well tolerated through 204 weeks of therapy.

AB - Objective: Combination antiretroviral therapy with lopinavir/ritonavir (LPV/r) has been highly effective in clinical trials. Results of long-term therapy with LPV/r-based regimens have not been previously reported. This study describes the 4-year (204-week) safety and antiretroviral activity of LPV/r-based treatment in antiretroviral-naive individuals. Design: Long-term, open-label follow-up of a phase II, prospective, randomized, multicenter trial. Methods: A group of 100 antiretroviral-naive HIV-infected patients were randomized to one of three blinded doses of LPV/r [200/100 mg (n = 16), 400/100 mg (n = 51), or 400/200 mg (n = 33)] with stavudine 40 mg and lamivudine 150 mg every 12 hours. After 48 weeks, LPV/r was dosed open-label at 400/100 mg every 12 hours with stavudine and lamivudine. Results: Mean baseline plasma HIV-1 RNA and CD4 cell count were 4.9 log 10 copies/ ml and 338 × 10 6 cells/l, respectively. At week 204, 72 patients remained on study, 70 of whom had HIV-1 RNA < 50 copies/ml (70% by intent-to-treat analysis). Twenty-eight patients discontinued therapy prior to week 204 because of adverse events (n = 10), lost to follow-up (n = 9), or other reasons (n = 9). Of 15 patients who met protocol-defined criteria for virologic failure, seven remained on the study regimen and their HIV-1 RNA was re-suppressed to < 50 copies/ml at week 204. Genotypic analysis of rebound viral isolates was available from 10 patients, including all eight patients who discontinued the study prematurely. No isolate demonstrated primary or active site mutations in protease. The most common adverse events were gastrointestinal symptoms and lipid elevations. Conclusions: LPV/r-based therapy provides durable antiretroviral response and is generally well tolerated through 204 weeks of therapy.

KW - Antiretroviral activity

KW - Cholesterol

KW - Lopinavir

KW - Ritonavir

KW - Safety

KW - Triglycerides

KW - Virologic failure

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