Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: Results from the EuroSIDA Study

Roger Paredes, Amanda Mocroft, Ole Kirk, Adriano Lazzarin, Simon E. Barton, Jan Van Lunzen, Terese L. Katzenstein, Francisco Antunes, Jens D. Lundgren, Bonaventura Clotet

Research output: Contribution to journalArticle

Abstract

Background: Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human immunodeficiency virus (HIV)-infected people. Objective: To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1- infected patients first starting protease inhibitor- or nonnucleoside retrotranscriptase inhibitor-containing HAART in Europe. Design: Prospective multicenter cohort study. Selling: Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999. Patients: A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients. Main Outcome Measure: Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat. Results: Most patients (80%) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4% at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard [RH], 0.76 per log higher; 95% confidence interval [CI], 0.69-0.84; P+ lymphocyte counts (RH per 50% higher, 1.09; 95% CI, 1.02-1.16; P = .008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95% CI, 1.03-1.61; P = .02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24% at 6 months). Antiretroviral- naive patients (RH, 0.50; 95% CI, 0.29-0.87; P = .01), older patients (RH, 0.86 per year older; 95% CI, 0.75-0.99; P = .04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95% CI, 0.44- 0.98; P = .04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95% CI, 0.99-1.40; P = .06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95% CI, 0.99-2.38; P = .06) were marginally significant predictors of a decreased hazard of ensuing virological failure. Conclusions: HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.

Original languageEnglish
Pages (from-to)1123-1132
Number of pages10
JournalArchives of Internal Medicine
Volume160
Issue number8
Publication statusPublished - Apr 24 2000

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Highly Active Antiretroviral Therapy
HIV
HIV-1
Confidence Intervals
RNA
Protease Inhibitors
Saquinavir
Gels
Intention to Treat Analysis
Lymphocyte Count
Nucleosides
Proportional Hazards Models
Multicenter Studies
Capsules
Cohort Studies
Outcome Assessment (Health Care)
Survival

ASJC Scopus subject areas

  • Internal Medicine

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Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe : Results from the EuroSIDA Study. / Paredes, Roger; Mocroft, Amanda; Kirk, Ole; Lazzarin, Adriano; Barton, Simon E.; Van Lunzen, Jan; Katzenstein, Terese L.; Antunes, Francisco; Lundgren, Jens D.; Clotet, Bonaventura.

In: Archives of Internal Medicine, Vol. 160, No. 8, 24.04.2000, p. 1123-1132.

Research output: Contribution to journalArticle

Paredes, R, Mocroft, A, Kirk, O, Lazzarin, A, Barton, SE, Van Lunzen, J, Katzenstein, TL, Antunes, F, Lundgren, JD & Clotet, B 2000, 'Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: Results from the EuroSIDA Study', Archives of Internal Medicine, vol. 160, no. 8, pp. 1123-1132.
Paredes, Roger ; Mocroft, Amanda ; Kirk, Ole ; Lazzarin, Adriano ; Barton, Simon E. ; Van Lunzen, Jan ; Katzenstein, Terese L. ; Antunes, Francisco ; Lundgren, Jens D. ; Clotet, Bonaventura. / Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe : Results from the EuroSIDA Study. In: Archives of Internal Medicine. 2000 ; Vol. 160, No. 8. pp. 1123-1132.
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title = "Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: Results from the EuroSIDA Study",
abstract = "Background: Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human immunodeficiency virus (HIV)-infected people. Objective: To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1- infected patients first starting protease inhibitor- or nonnucleoside retrotranscriptase inhibitor-containing HAART in Europe. Design: Prospective multicenter cohort study. Selling: Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999. Patients: A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients. Main Outcome Measure: Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat. Results: Most patients (80{\%}) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4{\%} at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard [RH], 0.76 per log higher; 95{\%} confidence interval [CI], 0.69-0.84; P+ lymphocyte counts (RH per 50{\%} higher, 1.09; 95{\%} CI, 1.02-1.16; P = .008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95{\%} CI, 1.03-1.61; P = .02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24{\%} at 6 months). Antiretroviral- naive patients (RH, 0.50; 95{\%} CI, 0.29-0.87; P = .01), older patients (RH, 0.86 per year older; 95{\%} CI, 0.75-0.99; P = .04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95{\%} CI, 0.44- 0.98; P = .04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95{\%} CI, 0.99-1.40; P = .06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95{\%} CI, 0.99-2.38; P = .06) were marginally significant predictors of a decreased hazard of ensuing virological failure. Conclusions: HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.",
author = "Roger Paredes and Amanda Mocroft and Ole Kirk and Adriano Lazzarin and Barton, {Simon E.} and {Van Lunzen}, Jan and Katzenstein, {Terese L.} and Francisco Antunes and Lundgren, {Jens D.} and Bonaventura Clotet",
year = "2000",
month = "4",
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TY - JOUR

T1 - Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe

T2 - Results from the EuroSIDA Study

AU - Paredes, Roger

AU - Mocroft, Amanda

AU - Kirk, Ole

AU - Lazzarin, Adriano

AU - Barton, Simon E.

AU - Van Lunzen, Jan

AU - Katzenstein, Terese L.

AU - Antunes, Francisco

AU - Lundgren, Jens D.

AU - Clotet, Bonaventura

PY - 2000/4/24

Y1 - 2000/4/24

N2 - Background: Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human immunodeficiency virus (HIV)-infected people. Objective: To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1- infected patients first starting protease inhibitor- or nonnucleoside retrotranscriptase inhibitor-containing HAART in Europe. Design: Prospective multicenter cohort study. Selling: Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999. Patients: A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients. Main Outcome Measure: Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat. Results: Most patients (80%) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4% at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard [RH], 0.76 per log higher; 95% confidence interval [CI], 0.69-0.84; P+ lymphocyte counts (RH per 50% higher, 1.09; 95% CI, 1.02-1.16; P = .008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95% CI, 1.03-1.61; P = .02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24% at 6 months). Antiretroviral- naive patients (RH, 0.50; 95% CI, 0.29-0.87; P = .01), older patients (RH, 0.86 per year older; 95% CI, 0.75-0.99; P = .04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95% CI, 0.44- 0.98; P = .04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95% CI, 0.99-1.40; P = .06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95% CI, 0.99-2.38; P = .06) were marginally significant predictors of a decreased hazard of ensuing virological failure. Conclusions: HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.

AB - Background: Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human immunodeficiency virus (HIV)-infected people. Objective: To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1- infected patients first starting protease inhibitor- or nonnucleoside retrotranscriptase inhibitor-containing HAART in Europe. Design: Prospective multicenter cohort study. Selling: Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999. Patients: A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients. Main Outcome Measure: Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat. Results: Most patients (80%) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4% at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard [RH], 0.76 per log higher; 95% confidence interval [CI], 0.69-0.84; P+ lymphocyte counts (RH per 50% higher, 1.09; 95% CI, 1.02-1.16; P = .008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95% CI, 1.03-1.61; P = .02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24% at 6 months). Antiretroviral- naive patients (RH, 0.50; 95% CI, 0.29-0.87; P = .01), older patients (RH, 0.86 per year older; 95% CI, 0.75-0.99; P = .04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95% CI, 0.44- 0.98; P = .04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95% CI, 0.99-1.40; P = .06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95% CI, 0.99-2.38; P = .06) were marginally significant predictors of a decreased hazard of ensuing virological failure. Conclusions: HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.

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