Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy

QUEST GW PROB3005

Bruno Hoen, David A. Cooper, Fiona C. Lampe, Luc Perrin, Nathan Clumeck, Andrew N. Phillips, Li Ean Goh, Stefan Lindback, Daniel Sereni, Brian Gazzard, Julio Montaner, Hans Jurgen Stellbrink, Adriano Lazzarin, Diane Ponscarme, Shlomo Staszewski, Lars Mathiesen, Don Smith, Robert Finlayson, Rainer Weber, Laurence Wegmann & 2 others George Janossy, Sabine Kinloch De Kinloch-De Loes

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background. Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit. Methods. After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks. Results. One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with ≤3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm3). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm3 (IQR, -1 to 283 cells/mm3); 84.2% of patients had a viral load ≤50 copies/ mL, and 44.7% of patients had a viral load ≤3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/ million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8+/CD38++ T cell count decreased from 459 cells/mm3 (IQR, 208-974 cells/mm 3) to 33 cells/mm3 (IQR, 19-75 cells/mm3). Baseline CD8+/CD38++ T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load ≤3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days). Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8+/CD38++ T cell count and cell-associated DNA level were predictive of achieving a viral load ≤3 copies/mL.

Original languageEnglish
Pages (from-to)381-390
Number of pages10
JournalClinical Infectious Diseases
Volume45
Issue number3
DOIs
Publication statusPublished - Aug 1 2007

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HIV-1
Viral Load
Virus Diseases
Therapeutics
Cell Count
DNA
RNA
CD4 Lymphocyte Count
T-Lymphocytes
Aftercare
Zidovudine
Lost to Follow-Up
Western Blotting

ASJC Scopus subject areas

  • Immunology

Cite this

Hoen, B., Cooper, D. A., Lampe, F. C., Perrin, L., Clumeck, N., Phillips, A. N., ... Kinloch-De Loes, S. K. D. (2007). Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005. Clinical Infectious Diseases, 45(3), 381-390. https://doi.org/10.1086/519428

Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy : QUEST GW PROB3005. / Hoen, Bruno; Cooper, David A.; Lampe, Fiona C.; Perrin, Luc; Clumeck, Nathan; Phillips, Andrew N.; Goh, Li Ean; Lindback, Stefan; Sereni, Daniel; Gazzard, Brian; Montaner, Julio; Stellbrink, Hans Jurgen; Lazzarin, Adriano; Ponscarme, Diane; Staszewski, Shlomo; Mathiesen, Lars; Smith, Don; Finlayson, Robert; Weber, Rainer; Wegmann, Laurence; Janossy, George; Kinloch-De Loes, Sabine Kinloch De.

In: Clinical Infectious Diseases, Vol. 45, No. 3, 01.08.2007, p. 381-390.

Research output: Contribution to journalArticle

Hoen, B, Cooper, DA, Lampe, FC, Perrin, L, Clumeck, N, Phillips, AN, Goh, LE, Lindback, S, Sereni, D, Gazzard, B, Montaner, J, Stellbrink, HJ, Lazzarin, A, Ponscarme, D, Staszewski, S, Mathiesen, L, Smith, D, Finlayson, R, Weber, R, Wegmann, L, Janossy, G & Kinloch-De Loes, SKD 2007, 'Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005', Clinical Infectious Diseases, vol. 45, no. 3, pp. 381-390. https://doi.org/10.1086/519428
Hoen, Bruno ; Cooper, David A. ; Lampe, Fiona C. ; Perrin, Luc ; Clumeck, Nathan ; Phillips, Andrew N. ; Goh, Li Ean ; Lindback, Stefan ; Sereni, Daniel ; Gazzard, Brian ; Montaner, Julio ; Stellbrink, Hans Jurgen ; Lazzarin, Adriano ; Ponscarme, Diane ; Staszewski, Shlomo ; Mathiesen, Lars ; Smith, Don ; Finlayson, Robert ; Weber, Rainer ; Wegmann, Laurence ; Janossy, George ; Kinloch-De Loes, Sabine Kinloch De. / Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy : QUEST GW PROB3005. In: Clinical Infectious Diseases. 2007 ; Vol. 45, No. 3. pp. 381-390.
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title = "Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005",
abstract = "Background. Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit. Methods. After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks. Results. One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with ≤3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm3). By week 48, 36{\%} of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm3 (IQR, -1 to 283 cells/mm3); 84.2{\%} of patients had a viral load ≤50 copies/ mL, and 44.7{\%} of patients had a viral load ≤3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/ million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3{\%} of patients had an undetectable RNA level, and 9.5{\%} of patients had an undetectable cell-associated DNA level. The median CD8+/CD38++ T cell count decreased from 459 cells/mm3 (IQR, 208-974 cells/mm 3) to 33 cells/mm3 (IQR, 19-75 cells/mm3). Baseline CD8+/CD38++ T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load ≤3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days). Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8+/CD38++ T cell count and cell-associated DNA level were predictive of achieving a viral load ≤3 copies/mL.",
author = "Bruno Hoen and Cooper, {David A.} and Lampe, {Fiona C.} and Luc Perrin and Nathan Clumeck and Phillips, {Andrew N.} and Goh, {Li Ean} and Stefan Lindback and Daniel Sereni and Brian Gazzard and Julio Montaner and Stellbrink, {Hans Jurgen} and Adriano Lazzarin and Diane Ponscarme and Shlomo Staszewski and Lars Mathiesen and Don Smith and Robert Finlayson and Rainer Weber and Laurence Wegmann and George Janossy and {Kinloch-De Loes}, {Sabine Kinloch De}",
year = "2007",
month = "8",
day = "1",
doi = "10.1086/519428",
language = "English",
volume = "45",
pages = "381--390",
journal = "Clinical Infectious Diseases",
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TY - JOUR

T1 - Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy

T2 - QUEST GW PROB3005

AU - Hoen, Bruno

AU - Cooper, David A.

AU - Lampe, Fiona C.

AU - Perrin, Luc

AU - Clumeck, Nathan

AU - Phillips, Andrew N.

AU - Goh, Li Ean

AU - Lindback, Stefan

AU - Sereni, Daniel

AU - Gazzard, Brian

AU - Montaner, Julio

AU - Stellbrink, Hans Jurgen

AU - Lazzarin, Adriano

AU - Ponscarme, Diane

AU - Staszewski, Shlomo

AU - Mathiesen, Lars

AU - Smith, Don

AU - Finlayson, Robert

AU - Weber, Rainer

AU - Wegmann, Laurence

AU - Janossy, George

AU - Kinloch-De Loes, Sabine Kinloch De

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Background. Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit. Methods. After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks. Results. One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with ≤3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm3). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm3 (IQR, -1 to 283 cells/mm3); 84.2% of patients had a viral load ≤50 copies/ mL, and 44.7% of patients had a viral load ≤3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/ million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8+/CD38++ T cell count decreased from 459 cells/mm3 (IQR, 208-974 cells/mm 3) to 33 cells/mm3 (IQR, 19-75 cells/mm3). Baseline CD8+/CD38++ T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load ≤3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days). Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8+/CD38++ T cell count and cell-associated DNA level were predictive of achieving a viral load ≤3 copies/mL.

AB - Background. Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit. Methods. After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks. Results. One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with ≤3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm3). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm3 (IQR, -1 to 283 cells/mm3); 84.2% of patients had a viral load ≤50 copies/ mL, and 44.7% of patients had a viral load ≤3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/ million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8+/CD38++ T cell count decreased from 459 cells/mm3 (IQR, 208-974 cells/mm 3) to 33 cells/mm3 (IQR, 19-75 cells/mm3). Baseline CD8+/CD38++ T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load ≤3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days). Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8+/CD38++ T cell count and cell-associated DNA level were predictive of achieving a viral load ≤3 copies/mL.

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