A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study)

a long-term randomised trial

Rodger David MacArthur, Richard M. Novak, Grace Peng, Li Chen, Ying Xiang, Katherine Huppler Hullsiek, Michael J. Kozal, Mary van den Berg-Wolf, Christopher Henely, Barry Schmetter, Marjorie Dehlinger

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Background: Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. Methods: Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00000922. Findings: 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1·02 (95% CI 0·79-1·31), 1·07 (0·80-1·41), 0·95 (0·66-1·37), and 0·66 (0·56-0·78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0·62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1·15 (0·91-1·45) and 0·87 (0·75-1·00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0·38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100 000 copies per mL or more (p=0·26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1·58; p<0·0001). Interpretation: Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.

Original languageEnglish (US)
Pages (from-to)2125-2135
Number of pages11
JournalLancet
Volume368
Issue number9553
DOIs
StatePublished - Dec 16 2006
Externally publishedYes

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Reverse Transcriptase Inhibitors
Protease Inhibitors
Nucleosides
CD4 Lymphocyte Count
Acquired Immunodeficiency Syndrome
Therapeutics
HIV
Intention to Treat Analysis
Poisons
Clinical Trials
RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study) : a long-term randomised trial. / MacArthur, Rodger David; Novak, Richard M.; Peng, Grace; Chen, Li; Xiang, Ying; Hullsiek, Katherine Huppler; Kozal, Michael J.; van den Berg-Wolf, Mary; Henely, Christopher; Schmetter, Barry; Dehlinger, Marjorie.

In: Lancet, Vol. 368, No. 9553, 16.12.2006, p. 2125-2135.

Research output: Contribution to journalArticle

MacArthur, Rodger David ; Novak, Richard M. ; Peng, Grace ; Chen, Li ; Xiang, Ying ; Hullsiek, Katherine Huppler ; Kozal, Michael J. ; van den Berg-Wolf, Mary ; Henely, Christopher ; Schmetter, Barry ; Dehlinger, Marjorie. / A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study) : a long-term randomised trial. In: Lancet. 2006 ; Vol. 368, No. 9553. pp. 2125-2135.
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abstract = "Background: Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. Methods: Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00000922. Findings: 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1·02 (95{\%} CI 0·79-1·31), 1·07 (0·80-1·41), 0·95 (0·66-1·37), and 0·66 (0·56-0·78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0·62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1·15 (0·91-1·45) and 0·87 (0·75-1·00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0·38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100 000 copies per mL or more (p=0·26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1·58; p<0·0001). Interpretation: Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.",
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TY - JOUR

T1 - A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study)

T2 - a long-term randomised trial

AU - MacArthur, Rodger David

AU - Novak, Richard M.

AU - Peng, Grace

AU - Chen, Li

AU - Xiang, Ying

AU - Hullsiek, Katherine Huppler

AU - Kozal, Michael J.

AU - van den Berg-Wolf, Mary

AU - Henely, Christopher

AU - Schmetter, Barry

AU - Dehlinger, Marjorie

PY - 2006/12/16

Y1 - 2006/12/16

N2 - Background: Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. Methods: Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00000922. Findings: 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1·02 (95% CI 0·79-1·31), 1·07 (0·80-1·41), 0·95 (0·66-1·37), and 0·66 (0·56-0·78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0·62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1·15 (0·91-1·45) and 0·87 (0·75-1·00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0·38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100 000 copies per mL or more (p=0·26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1·58; p<0·0001). Interpretation: Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.

AB - Background: Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. Methods: Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00000922. Findings: 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1·02 (95% CI 0·79-1·31), 1·07 (0·80-1·41), 0·95 (0·66-1·37), and 0·66 (0·56-0·78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0·62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1·15 (0·91-1·45) and 0·87 (0·75-1·00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0·38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100 000 copies per mL or more (p=0·26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1·58; p<0·0001). Interpretation: Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.

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