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Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients

Monforte, Antonella d'Arminioa; Lepri, Alessandro Cozzib; Rezza, Giovannic; Pezzotti, Patrizioc; Antinori, Andread; Phillips, Andrew N.b; Angarano, Gioacchinoe; Colangeli, Vincenzof; Luca, Andrea Deg; Ippolito, Giusepped; Caggese, Lilianah; Soscia, Fabrizioi; Filice, Gaetanoj; Gritti, Francescok; Narciso, Pasqualed; Tirelli, Umbertol; Moroni, Mauro*for the I.CO.N.A. Study Group


Objective: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment.

Methods: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points.

Results: Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9–28.9] due to toxicity and 7.6% (95% CI, 4.9–10.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32–0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10–3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09–7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80–0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74–5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06–0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04–1.26 versus hard-gell saquinavir).

Conclusions: If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

From the aInstitute of Infectious and Tropical Diseases, University of Milan, Milan, Italy, the bRoyal Free Centre for HIV Medicine, Royal Free & Universiy College Medical School, London, UK, the cIstituto Superiore di Sanità, Rome, the dIRCCS L. Spallanzani, Rome, the eInstitute of Infectious Diseases, University of Bari, Bari, the fInstitute of Infectious Diseases, University of Bologna, Bologna, the gClinic of Infectious Diseases, Cattolica University, Rome, the hDepartment of Infectious Diseases, Niguarda Hospital, Milan, the iAIDS Center, Latina Hospital, Latina, the jInstitute of Infectious Diseases, University of Pavia, Pavia, the kDepartment of Infectious Diseases, Maggiore Hospital, Bologna and the lOncology Center of Aviano, Pordenone, Italy. *See Appendix.

Sponsorship: The I.CO.N.A. network is supported by an unrestricted educational grant provided by Glaxo-Wellcome Italy.

Correspondence to Antonella d'Arminio Monforte, Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, via GB Grassi, 74, 20157 Milan, Italy. E-mail:

Received: 16 March 1999;

revised: 21 June 1999; accepted: 23 November 1999.

© 2000 Lippincott Williams & Wilkins, Inc.