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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
Roger Paredes, MD;
Amanda Mocroft, PhD;
Ole Kirk, MD;
Adriano Lazzarin, MD;
Simon E. Barton, MD;
Jan van Lunzen, MD;
Terese L. Katzenstein, PhD;
Francisco Antunes, PhD;
Jens D. Lundgren, MD, DMSc;
Bonaventura Clotet, PhD;
for the EuroSIDA Study Group
Arch Intern Med. 2000;160:1123-1132.
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.
Setting 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<.001) and those taking saquinavir mesylate hard gel as a single protease inhibitor (RH, 0.62; 95% CI, 0.47-0.82; P<.001) were less likely to reach undetectable HIV-1 RNA levels. Conversely, higher CD4+ 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.
From the Retrovirology Laboratory "irsiCaixa" and HIV Clinical Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain (Drs Paredes and Clotet); the Department of Primary Care and Population Sciences, Royal Free Hospital School of Medicine, London, England (Dr Mocroft); the Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark (Drs Kirk and Lundgren); the Department of Infectious Diseases, Ospedale San Raffaele, Milan, Italy (Dr Lazzarin); the Directorate of HIV/GUM, Chelsea and Westminster Hospital, London (Dr Barton); the Department of Medicine, University Hospital Eppendorf, Hamburg, Germany (Dr van Lunzen); the Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark (Dr Katzenstein); and the Clínica de Doenças Infecciosas, Hospital de Santa Maria, Lisbon, Portugal (Dr Antunes).
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