Combination therapy with efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors in children infected with human immunodeficiency virus type 1

Stuart E. Starr, Courtney V. Fletcher, Stephen A. Spector, Florence H. Yong, Terence Fenton, Richard C. Brundage, Douglas Manion, Nancy M. Ruiz, Merril Gersten, Mark Becker, James McNamara, Lynne M. Mofenson, Lynette Purdue, Suzanne Siminski, Bobie Graham, David M. Kornhauser, William Fiske, Carol Vincent, Harold W. Lischner, Wayne M. DanknerPatricia M. Flynn

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Background: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency torus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse- transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. Methods: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. Results: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. Conclusions: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.

Original languageEnglish (US)
Pages (from-to)1874-1881
Number of pages8
JournalNew England Journal of Medicine
Volume341
Issue number25
DOIs
StatePublished - Dec 16 1999

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efavirenz
Nelfinavir
Reverse Transcriptase Inhibitors
Nucleosides
HIV-1
RNA
Therapeutics
Antiviral Agents
Intention to Treat Analysis
Lymphocyte Subsets
Exanthema
Neutropenia

ASJC Scopus subject areas

  • Medicine(all)

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Combination therapy with efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors in children infected with human immunodeficiency virus type 1. / Starr, Stuart E.; Fletcher, Courtney V.; Spector, Stephen A.; Yong, Florence H.; Fenton, Terence; Brundage, Richard C.; Manion, Douglas; Ruiz, Nancy M.; Gersten, Merril; Becker, Mark; McNamara, James; Mofenson, Lynne M.; Purdue, Lynette; Siminski, Suzanne; Graham, Bobie; Kornhauser, David M.; Fiske, William; Vincent, Carol; Lischner, Harold W.; Dankner, Wayne M.; Flynn, Patricia M.

In: New England Journal of Medicine, Vol. 341, No. 25, 16.12.1999, p. 1874-1881.

Research output: Contribution to journalArticle

Starr, SE, Fletcher, CV, Spector, SA, Yong, FH, Fenton, T, Brundage, RC, Manion, D, Ruiz, NM, Gersten, M, Becker, M, McNamara, J, Mofenson, LM, Purdue, L, Siminski, S, Graham, B, Kornhauser, DM, Fiske, W, Vincent, C, Lischner, HW, Dankner, WM & Flynn, PM 1999, 'Combination therapy with efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors in children infected with human immunodeficiency virus type 1', New England Journal of Medicine, vol. 341, no. 25, pp. 1874-1881. https://doi.org/10.1056/NEJM199912163412502
Starr, Stuart E. ; Fletcher, Courtney V. ; Spector, Stephen A. ; Yong, Florence H. ; Fenton, Terence ; Brundage, Richard C. ; Manion, Douglas ; Ruiz, Nancy M. ; Gersten, Merril ; Becker, Mark ; McNamara, James ; Mofenson, Lynne M. ; Purdue, Lynette ; Siminski, Suzanne ; Graham, Bobie ; Kornhauser, David M. ; Fiske, William ; Vincent, Carol ; Lischner, Harold W. ; Dankner, Wayne M. ; Flynn, Patricia M. / Combination therapy with efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors in children infected with human immunodeficiency virus type 1. In: New England Journal of Medicine. 1999 ; Vol. 341, No. 25. pp. 1874-1881.
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abstract = "Background: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency torus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse- transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. Methods: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. Results: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. Conclusions: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.",
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T1 - Combination therapy with efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors in children infected with human immunodeficiency virus type 1

AU - Starr, Stuart E.

AU - Fletcher, Courtney V.

AU - Spector, Stephen A.

AU - Yong, Florence H.

AU - Fenton, Terence

AU - Brundage, Richard C.

AU - Manion, Douglas

AU - Ruiz, Nancy M.

AU - Gersten, Merril

AU - Becker, Mark

AU - McNamara, James

AU - Mofenson, Lynne M.

AU - Purdue, Lynette

AU - Siminski, Suzanne

AU - Graham, Bobie

AU - Kornhauser, David M.

AU - Fiske, William

AU - Vincent, Carol

AU - Lischner, Harold W.

AU - Dankner, Wayne M.

AU - Flynn, Patricia M.

PY - 1999/12/16

Y1 - 1999/12/16

N2 - Background: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency torus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse- transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. Methods: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. Results: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. Conclusions: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.

AB - Background: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency torus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse- transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. Methods: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. Results: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. Conclusions: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse- transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.

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