Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in ... View Full Text


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Article Info

DATE

2017-03-15

AUTHORS

Maria Concetta Postorino, Mattia Prosperi, Emanuele Focà, Eugenia Quiros-Roldan, Elisa Di Filippo, Franco Maggiolo, Alberto Borghetti, Nicoletta Ladisa, Massimo Di Pietro, Andrea Gori, Laura Sighinolfi, Angelo Pan, Nicola Mazzini, Carlo Torti

ABSTRACT

BackgroundAtazanavir (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.MethodsAn 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.Results436 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 Log10 copies/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 Log10 higher [HR: 1.319, 95% CI 1.047–1.662, p = 0.0188].ConclusionsIntravenous 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. More... »

PAGES

212

Journal

TITLE

BMC Infectious Diseases

ISSUE

1

VOLUME

17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12879-017-2322-z

DOI

http://dx.doi.org/10.1186/s12879-017-2322-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084250363

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28298195


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31 schema:description BackgroundAtazanavir (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.MethodsAn 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.Results436 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 Log10 copies/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 Log10 higher [HR: 1.319, 95% CI 1.047–1.662, p = 0.0188].ConclusionsIntravenous 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.
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