title: Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort.
abstract: Atazanavir (ATV) not boosted by ritonavir (uATV) has been frequently used in the past for switching combination antiretroviral therapy (cART). However, the clinical outcomes and predictors of such strategy are unknown.
  
  
  
  An observational study was carried out on the Italian MASTER, selecting HIV infected patients on cART switching to an uATV-containing regimen. Baseline was set as the last visit before uATV initiation. In the primary analysis, a composite clinical end-point was defined as the first occurring of any condition among: liver, cardiovascular, kidney, diabetes, non AIDS related cancer or death events. Incidence of AIDS events and incidence of composite clinical end-point were estimated. Kaplan-Meier and multivariable Cox regression analysis were used to assess predictors of the composite clinical end-point.
  
  
  
  436 patients were observed. The majority of patients were males (61.5%) and Italians (85.3%), mean age was 42.7 years (IQR: 37.7-42), the most frequent route of transmission was heterosexual intercourse (47%), followed by injection drug use (25%) and homosexual contact (24%); the rate of HCV-Ab positivity was 16.3%. Patients were observed for a median time of 882 days (IQR: 252-1,769) under uATV. We recorded 93 clinical events (3 cardiovascular events, 20 kidney diseases, 33 liver diseases, 9 non AIDS related cancers, 21 diabetes, 7 AIDS events), and 19 deaths, accounting for an incidence of 3.7 (composite) events per 100 PYFU. At multivariable analysis, factors associated with the composite clinical end-point were intravenous drug use as risk factor for HIV acquisition vs. heterosexual intercourses [HR: 2.608, 95% CI 1.31-5.19, p = 0.0063], HIV RNA per Log10copies/ml higher [HR: 1.612, 95% CI 1.278-2.034, p < 0.0001], number of switches in the nucleoside/nucleotide (NRTI) backbone of cART (performed to compose the uATV regimen under study or occurred in the past) per each more [HR: 1.085, 95% CI 1.025-1.15, p = 0.0051], Fib-4 score per unit higher [HR: 1.03, 95% CI 1.018-1.043, p < 0.0001] and Neutrophil/lymphocytes ratio (NLR inflammation score) per Log10higher [HR: 1.319, 95% CI 1.047-1.662, p = 0.0188].
  
  
  
  Intravenous drug users with high HIV RNA, high Fib-4 levels and more heavily exposed to antiretroviral drugs appeared to be more at risk of clinical events. Interestingly, high levels of inflammation measured through NLR, were also associated with clinical events. So, these patients should be monitored more strictly.
authors.affiliation: Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Postorino
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, Gainesville, USA.
authors.forename: Mattia
authors.initials: M
authors.lastname: Prosperi
authors.affiliation: University Department of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, Brescia, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Focà
authors.affiliation: University Department of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, Brescia, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros-Roldan
authors.affiliation: Clinic of Infectious Diseases of "Papa Giovanni XXIII" Hospital of Bergamo, Bergamo, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Di Filippo
authors.affiliation: Clinic of Infectious Diseases of "Papa Giovanni XXIII" Hospital of Bergamo, Bergamo, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
authors.affiliation: Institute of Clinical Infectious Diseases of Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Borghetti
authors.affiliation: Clinic of Infectious Diseases, University of Bari, Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.affiliation: Clinic of Infectious Diseases of "Azienda Ospedaliera S.M. Annunziata", Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Pietro
authors.affiliation: Clinic of Infectious Diseases, San Gerardo de' Tintori Hospital, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.affiliation: Clinic of Infectious Diseases of "Azienda Ospedaliera S. Anna" of Ferrara, Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sighinolfi
authors.affiliation: Clinic of Infectious Diseases of "Istituti Ospitalieri" of Cremona, Cremona, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Pan
authors.affiliation: MISI Foundation, Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mazzini
authors.affiliation: Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy. torti@unicz.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000453:epidemiology*; D008107:Liver Diseases / Q000453:epidemiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate
keywords: Atazanavir; Clinical events; HIV; Ritonavir; Systemic inflammation scores