The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility

A prospective cohort analysis

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

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI). Design: Analysis of a prospective clinical trial cohort. Patients: NNRTI-naive patients failing a stable antiretroviral regimen. Measurements: HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50%) of < 0.4. Results: The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 × 106 cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29%. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log10 HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 × 106 cells/l greater in patients with hypersusceptible virus (P ≤ 0.1). Conclusion: NNRTI hypersusceptibility occurred in more than 20% of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.

Original languageEnglish (US)
JournalAIDS
Volume16
Issue number15
DOIs
StatePublished - Oct 18 2002
Externally publishedYes

Fingerprint

Reverse Transcriptase Inhibitors
Cohort Studies
HIV
RNA
efavirenz
CD4 Lymphocyte Count
Nucleosides
Linear Models
Viruses
Inhibitory Concentration 50
HIV-1
Clinical Trials
Phenotype

Keywords

  • Antiretroviral therapy
  • Clinical trials
  • HIV-1
  • Hypersusceptibility
  • Non-nucleoside reverse transcriptase inhibitor
  • Phenotypic resistance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility : A prospective cohort analysis. / Haubrich, Richard H.; Kemper, Carol A.; Hellmann, Nicholas S.; Keiser, Philip; Witt, Mallory D.; Forthal, Donald N.; Leedom, John; Leibowitz, Matthew; Whitcomb, Jeannette M.; Richman, Douglas; McCutchan, J. Allen.

In: AIDS, Vol. 16, No. 15, 18.10.2002.

Research output: Contribution to journalArticle

Haubrich, RH, Kemper, CA, Hellmann, NS, Keiser, P, Witt, MD, Forthal, DN, Leedom, J, Leibowitz, M, Whitcomb, JM, Richman, D & McCutchan, JA 2002, 'The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility: A prospective cohort analysis', AIDS, vol. 16, no. 15. https://doi.org/10.1097/00002030-200210180-00001
Haubrich, Richard H. ; Kemper, Carol A. ; Hellmann, Nicholas S. ; Keiser, Philip ; Witt, Mallory D. ; Forthal, Donald N. ; Leedom, John ; Leibowitz, Matthew ; Whitcomb, Jeannette M. ; Richman, Douglas ; McCutchan, J. Allen. / The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility : A prospective cohort analysis. In: AIDS. 2002 ; Vol. 16, No. 15.
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abstract = "Objective: To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI). Design: Analysis of a prospective clinical trial cohort. Patients: NNRTI-naive patients failing a stable antiretroviral regimen. Measurements: HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50{\%}) of < 0.4. Results: The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 × 106 cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29{\%}. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log10 HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 × 106 cells/l greater in patients with hypersusceptible virus (P ≤ 0.1). Conclusion: NNRTI hypersusceptibility occurred in more than 20{\%} of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.",
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T1 - The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility

T2 - A prospective cohort analysis

AU - Haubrich, Richard H.

AU - Kemper, Carol A.

AU - Hellmann, Nicholas S.

AU - Keiser, Philip

AU - Witt, Mallory D.

AU - Forthal, Donald N.

AU - Leedom, John

AU - Leibowitz, Matthew

AU - Whitcomb, Jeannette M.

AU - Richman, Douglas

AU - McCutchan, J. Allen

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N2 - Objective: To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI). Design: Analysis of a prospective clinical trial cohort. Patients: NNRTI-naive patients failing a stable antiretroviral regimen. Measurements: HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50%) of < 0.4. Results: The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 × 106 cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29%. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log10 HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 × 106 cells/l greater in patients with hypersusceptible virus (P ≤ 0.1). Conclusion: NNRTI hypersusceptibility occurred in more than 20% of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.

AB - Objective: To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI). Design: Analysis of a prospective clinical trial cohort. Patients: NNRTI-naive patients failing a stable antiretroviral regimen. Measurements: HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50%) of < 0.4. Results: The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 × 106 cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29%. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log10 HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 × 106 cells/l greater in patients with hypersusceptible virus (P ≤ 0.1). Conclusion: NNRTI hypersusceptibility occurred in more than 20% of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.

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