Incidence and Risk Factors for Severe Bacterial Infections in People Living with HIV. ANRS CO3 Aquitaine Cohort, 2000-2012.

Amandine Collin,Yann Gérard,Pierre Duffau,Estibaliz Lazaro,François Dabis,Mathias Bruyand,Fabrice Bonnet,Charles Cazanave,Marie-Anne Vandenhende,Fabien Le Marec,Antonio Guilherme Pacheco

doi:10.1371/journal.pone.0152970

Abstract

Severe non-AIDS bacterial infections (SBI) are the leading cause of hospital admissions among people living with HIV (PLHIV) in industrialized countries. We aimed to estimate the incidence of SBI and their risk factors in a large prospective cohort of PLHIV patients over a 13-year period in France. Patients followed up in the ANRS CO3 Aquitaine cohort between 2000 and 2012 were eligible; SBI was defined as a clinical diagnosis associated with hospitalization of ≥48 hours or death. Survival analysis was conducted to identify risk factors for SBI.Total follow-up duration was 39,256 person-years [PY] (31,370 PY on antiretroviral treatment [ART]). The incidence of SBI decreased from 26.7/1000 PY [95% CI: 22.9–30.5] over the period 2000–2002 to 11.9/1000 PY [10.1–13.8] in 2009–2012 (p <0.0001). Factors independently associated to increased risk of SBI were: plasma HIVRNA>50 copies/mL (Hazard Ratio [HR] = 5.1, 95% Confidence Interval: 4.2–6.2), CD4 count <500 cells/mm3 and CD4/CD8 ratio <0.8 (with a dose-response relationship for both markers), history of cancer (HR = 1.4 [1.0–1.9]), AIDS stage (HR = 1.7 [1.3–2.1]) and HCV coinfection (HR = 1.4, [1.1–1.6]). HIV-positive patients with diabetes were more prone to SBI (HR = 1.6 [0.9–2.6]). Incidence of SBI decreased over a 13-year period due to the improvement in the virological and immune status of PLHIV on ART. Risk factors for SBI include low CD4 count and detectable HIV RNA, but also CD4/CD8 ratio, HCV coinfection, history of cancer and diabetes, comorbid conditions that have been frequent among PLHIV in recent years.

Highlights

Mortality and incidence of AIDS-defining infections have dramatically decreased since the late 90’s with the advent of antiretroviral therapy (ART) [1,2]
In previous studies conducted in the ANRS CO3 Aquitaine Cohort, south-western France, we have shown that non-AIDS infections accounted for more than 25% of hospitalizations in people living with HIV (PLHIV), representing the leading cause of severe morbidity in this population
HCV coinfection, low CD4 count, low CD4/CD8 count, HIVRNA >50 copies/mL were independently associated with an increased risk of developing severe pneumonia. In this large observational and prospective study including more than 5,000 patients and with accurate diagnostic and validation procedures, we report that the incidence of non-AIDS severe infections significantly decreased over a 13-year-period in the ART era

Summary

Introduction

Mortality and incidence of AIDS-defining infections have dramatically decreased since the late 90’s with the advent of antiretroviral therapy (ART) [1,2]. The declining trend in incidence of non-AIDS infections has been less pronounced. In a national study conducted in France in 2010 on causes of death, nine per cent of HIV-infected patients died from non-AIDS infections (versus 4% in 2005 and 7% in 2000 in comparable surveys) [3]. In previous studies conducted in the ANRS CO3 Aquitaine Cohort, south-western France, we have shown that non-AIDS infections accounted for more than 25% of hospitalizations in people living with HIV (PLHIV), representing the leading cause of severe morbidity in this population. Bacterial infections were the most frequent, representing 15% of causes of hospitalizations [4,5]. A recent meta-analysis has shown that bacterial infections were the second cause of hospital admission worldwide after AIDS-related illnesses [6]

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