title: Treatment Modifications and Treatment-Limiting Toxicities or Side Effects: Risk Factors and Temporal Trends.
abstract: Combined antiretroviral treatment (cART) modifications are often required due to treatment failure or side effects. We investigate cART regimens' durability, frequency of treatment-limiting adverse events, and potential risk factors and temporal trends. Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). Statistical analyses were based on survival techniques, allowing for multiple contributions per individual. Overall, 2,756 individuals, aged >15 years, initiated cART. cART regimens were grouped by their initiation date into four calendar periods (1995-1998, 1999-2002, 2003-2006, and 2007+). Median [95% confidence interval (CI)] time to first treatment modification was 2.11 (1.95-2.33) years; cumulative probabilities at 1 year were 31.6%, 29.0%, 33.1%, and 29.6% for the four periods, respectively. cART modifications were less frequent in more recent years (adjusted HR=0.96 per year; p<0.001). Longer treatment duration was associated with lower HIV-RNA, higher CD4 counts, and being previously ART naive. cART modifications due to treatment failure became less frequent in recent years (adjusted HR=0.91 per year; p<0.001). Estimated (95% CI) 1 year cumulative probabilities of treatment-limiting side effects were 16.4% (12.0-21.3%), 19.3% (15.6-23.3%), 24.9% (20.3-29.7%), and 21.1% (13.4-29.9%) for the four periods, respectively, with no significant temporal trends. Risk of side effects was lower in nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens or triple nucleoside reverse transcriptase inhibitor (NRTI)-based cART regimens. Treatment modifications have become less frequent in more recent years. This could be partly attributed to the lower risk for side effects of NNRTI-based cART regimens and mainly to the improved efficacy of newer drugs. However, the rate of drugs substitutions due to adverse events remains substantially high.
authors.affiliation: 1 Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School , Athens, Greece .
authors.forename: Nikos
authors.initials: N
authors.lastname: Pantazis
authors.affiliation: 2 First Department of Propaedeutic Medicine, University of Athens , Athens, Greece .
authors.forename: Mina
authors.initials: M
authors.lastname: Psichogiou
authors.affiliation: 3 AIDS Unit, Clinic of Venereologic and Dermatologic Diseases, Athens Medical School, "Syngros" Hospital , Athens, Greece .
authors.forename: Vassilios
authors.initials: V
authors.lastname: Paparizos
authors.affiliation: 4 First Department of Internal Medicine and Infectious Diseases Unit, General Hospital of Athens "G. Gennimatas ," Athens, Greece .
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Gargalianos
authors.affiliation: 5 Third Department of Internal Medicine-Infectious Diseases Unit, Red Cross General Hospital , Athens, Greece .
authors.forename: Maria
authors.initials: M
authors.lastname: Chini
authors.affiliation: 6 Fourth Department of Internal Medicine, Athens Medical School, "Attikon" University General Hospital , Athens, Greece .
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Protopapas
authors.affiliation: 7 Infectious Diseases Unit, Department of Pathophysiology, "Laikon" Athens General Hospital and Medical School, National and Kapodistrian University of Athens , Athens, Greece .
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Sipsas
authors.affiliation: 8 Department of Internal Medicine and Infectious Diseases, Patras University General Hospital , Patras, Greece .
authors.forename: George
authors.initials: G
authors.lastname: Panos
authors.affiliation: 9 Infectious Diseases Unit, "Tzaneion" General Hospital of Piraeus , Athens, Greece .
authors.forename: George
authors.initials: G
authors.lastname: Chrysos
authors.affiliation: 10 HIV Unit, Second Department of Internal Medicine, Athens Medical School, "Hippokration" University General Hospital , Athens, Greece .
authors.forename: Helen
authors.initials: H
authors.lastname: Sambatakou
authors.affiliation: 11 Blood Centre, National Reference Centre for Congenital Bleeding Disorders, "Laikon" Athens General Hospital , Athens, Greece .
authors.forename: Olga
authors.initials: O
authors.lastname: Katsarou
authors.affiliation: 1 Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School , Athens, Greece .
authors.forename: Giota
authors.initials: G
authors.lastname: Touloumi
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D028761:Withholding Treatment / Q000706:statistics & numerical data