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Interruption of Highly Active Antiretroviral Therapy in HIV Clinical Practice: Results From the Italian Cohort of Antiretroviral-Naive Patients

Monforte, Antonella d'Arminio MD*; Cozzi-Lepri, Alessandro PhD; Phillips, Andrew PhD; De Luca, Andrea MD; Murri, Rita MD; Mussini, Cristina MD§; Grossi, Paolo MD; Galli, Andrea MD; Zauli, Tiziano MD#; Montroni, Maria MD**; Tundo, Paolo MD††; Moroni, Mauro MD*for the Italian Cohort of Antiretroviral-Naive Patients Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 1st, 2005 - Volume 38 - Issue 4 - p 407-416
doi: 10.1097/01.qai.0000147529.57240.b0
Clinical Science

Objectives: To investigate the frequency of a first therapy interruption (TI) ≥12 weeks, to identify the factors associated with TI and with therapy resumption, and to compare the risk of developing clinical events during TI and during continuous therapy.

Methods: Observational study of 3142 patients who started a first highly active antiretroviral therapy (HAART) regimen. End points were time to (1) first TI of ≥12 weeks, (2) subsequent therapy resumption, and (3) development of new AIDS-related events or death.

Results: Over a median follow-up period of 41 months (interquartile range: 18-60 months), 721 patients (22.9%) interrupted HAART for ≥12 weeks, with a probability of 28.6% (95% confidence interval [CI]: 26.7-30.6) by 4 years from the date of therapy initiation. Patient decision (47.4%) and toxicity (24.0%) were the main reasons for TI. Women, injection drug users, and patients with a higher current CD4 cell count were more likely to interrupt. The median time to therapy resumption was 12 months (95% CI: 11-14). The higher the current CD4 count, the slower was the rate of resuming therapy; conversely, patients who stopped because of failure and those with a pre-HAART viral load >100,000 copies/mL resumed therapy sooner. Two hundred eighty-one patients experienced clinical progression at a rate of 2.6 per 100 person-years (pys) (95% CI: 2.3-3.0) while patients were on therapy and 3.5 per 100 pys (95% CI: 2.4-4.8) during TI. The adjusted relative hazard of clinical progression associated with TI was 2.75 (95% CI: 1.14-6.65; P = 0.03).

Conclusions: TI occurring in clinical practice is associated with an increased risk of clinical progression; hence, it should be discouraged outside strictly experimental settings.

From the *Istituto di Malattie Infettive e Tropicali, Università di Milano, Milano, Italy; †Royal Free and University College Medical School, London, United Kingdom; ‡Istituto di Clinica delle Malattie Infettive, Università Cattolica del S. Cuore, Roma, Italy; §Clinica di Malattie Infettive, Università di Modena, Modena, Italy; ∥Divisione di Malattie Infettive, Ospedale di Varese, Varese, Italy; ¶Clinica di Malattie Infettive, Università Vita e Salute, Milano, Italy; #Divisione di Malattie Infettive, Ospedale di Ravenna, Ravenna, Italy; **Cattedra di Immunologia Clinica, Università di Ancona, Ancona, Italy; and ††Divisione di Malattie Infettive, Ospedale di Lecce, Lecce, Italy.

Received for publication March 18, 2004;

accepted September 28, 2004.

The Italian Cohort of Antiretroviral-Naive Patients study is supported by an unrestricted educational grant from GlaxoSmithKline Italy.

Reprints: 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:

© 2005 Lippincott Williams & Wilkins, Inc.