A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575

Richard H. Haubrich, Carol A. Kemper, Nicholas S. Hellmann, Philip Keiser, Mallory D. Witt, Jeremiah G. Tilles, Donald N. Forthal, John Leedom, Matthew Leibowitz, J. Allen McCutchan, Douglas D. Richman

Research output: Contribution to journalArticle

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Abstract

Objective: To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy. Design: A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. Method: Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures. Results: At baseline, median CD4 cell count was 277 × 10 6 cells/l and HIV RNA was 10 000 copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log 10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48%) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value. Conclusions: Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalAIDS
Volume19
Issue number3
StatePublished - Feb 18 2005
Externally publishedYes

Fingerprint

Reverse Transcriptase Inhibitors
Standard of Care
Prospective Studies
RNA
Phenotype
Nucleosides
HIV
Protease Inhibitors
HIV Protease Inhibitors
Therapeutics
CD4 Lymphocyte Count
Pharmaceutical Preparations
Multicenter Studies
Viruses

Keywords

  • Antiretroviral therapy
  • Drug resistance
  • Phenotype susceptibility testing
  • Virological outcome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Haubrich, R. H., Kemper, C. A., Hellmann, N. S., Keiser, P., Witt, M. D., Tilles, J. G., ... Richman, D. D. (2005). A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575. AIDS, 19(3), 295-302.

A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy : CCTG 575. / Haubrich, Richard H.; Kemper, Carol A.; Hellmann, Nicholas S.; Keiser, Philip; Witt, Mallory D.; Tilles, Jeremiah G.; Forthal, Donald N.; Leedom, John; Leibowitz, Matthew; McCutchan, J. Allen; Richman, Douglas D.

In: AIDS, Vol. 19, No. 3, 18.02.2005, p. 295-302.

Research output: Contribution to journalArticle

Haubrich, RH, Kemper, CA, Hellmann, NS, Keiser, P, Witt, MD, Tilles, JG, Forthal, DN, Leedom, J, Leibowitz, M, McCutchan, JA & Richman, DD 2005, 'A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575', AIDS, vol. 19, no. 3, pp. 295-302.
Haubrich, Richard H. ; Kemper, Carol A. ; Hellmann, Nicholas S. ; Keiser, Philip ; Witt, Mallory D. ; Tilles, Jeremiah G. ; Forthal, Donald N. ; Leedom, John ; Leibowitz, Matthew ; McCutchan, J. Allen ; Richman, Douglas D. / A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy : CCTG 575. In: AIDS. 2005 ; Vol. 19, No. 3. pp. 295-302.
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abstract = "Objective: To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy. Design: A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. Method: Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures. Results: At baseline, median CD4 cell count was 277 × 10 6 cells/l and HIV RNA was 10 000 copies/ml; 76{\%} had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log 10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48{\%}) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50{\%} of the PHENO versus 17{\%} of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value. Conclusions: Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.",
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T1 - A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy

T2 - CCTG 575

AU - Haubrich, Richard H.

AU - Kemper, Carol A.

AU - Hellmann, Nicholas S.

AU - Keiser, Philip

AU - Witt, Mallory D.

AU - Tilles, Jeremiah G.

AU - Forthal, Donald N.

AU - Leedom, John

AU - Leibowitz, Matthew

AU - McCutchan, J. Allen

AU - Richman, Douglas D.

PY - 2005/2/18

Y1 - 2005/2/18

N2 - Objective: To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy. Design: A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. Method: Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures. Results: At baseline, median CD4 cell count was 277 × 10 6 cells/l and HIV RNA was 10 000 copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log 10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48%) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value. Conclusions: Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.

AB - Objective: To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy. Design: A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. Method: Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures. Results: At baseline, median CD4 cell count was 277 × 10 6 cells/l and HIV RNA was 10 000 copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log 10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48%) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value. Conclusions: Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.

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KW - Drug resistance

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KW - Virological outcome

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