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Excess mortality related to circulatory system diseases and diabetes mellitus among Italian AIDS patients vs. non-AIDS population: a population-based cohort study using the multiple causes-of-death approach

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      Abstract

      BackgroundChronic diseases, chiefly cancers and circulatory system diseases (CSDs), have become the leading non-AIDS-related causes of death among HIV-infected people, as in the general population. After our previous report of an excess mortality for several non-AIDS-defining cancers, we now aim to assess whether people with AIDS (PWA) experience also an increased mortality for CSDs and diabetes mellitus (DM), as compared to the non-AIDS general population (non-PWA).MethodsA nationwide, population-based, retrospective cohort study was conducted including 5285 Italians, aged 15−74 years, who were diagnosed with AIDS between 2006 and 2011. Multiple cause-of-death (MCoD) data, i.e. all conditions reported in death certificates, were retrieved through record-linkage with the National Register of Causes of Death up to 2011. Using MCoD data, sex- and age-standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated by dividing the observed number of PWA reporting a specific disease among MCoD to the expected number, estimated on the basis of mortality rates (based on MCoD) of non-PWA.ResultsAmong 1229 deceased PWA, CSDs were mentioned in 201 (16.4%) certificates and DM in 46 (3.7%) certificates among the various causes of death. These values corresponded to a 13-fold higher mortality related to CSDs (95% CI 10.8–14.4) and DM (95% CI: 9.5–17.4) as compared to 952,019 deceased non-PWA. Among CSDs, statistically significant excess mortality emerged for hypertension (23 deaths, SMR = 6.3, 95% CI: 4.0–9.4), ischemic heart diseases (39 deaths, SMR = 6.1, 95% CI: 4.4–8.4), other forms of heart diseases (88 deaths, SMR = 13.4, 95% CI: 10.8–16.5), and cerebrovascular diseases (42 deaths, SMR = 13.4, 95% CI: 9.7–18.2). The SMRs were particularly elevated among PWA aged < 50 years and those infected through drug injection.ConclusionsThe use of MCoD data disclosed the fairly high mortality excess related to several CSDs and DM among Italian PWA as compared to non-PWA. Study findings also indicate to start preventive strategies for such diseases at a younger age among AIDS patients than in the general population and with focus on drug users.

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      Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration.

      With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011.
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        Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies.

        We examined specific causes of mortality in human immunodeficiency virus type 1 (HIV-1)-infected patients who initiated antiretroviral therapy (ART) in Europe and North America from 1996 through 2006, and we quantified associations of prognostic factors with cause-specific mortality. We retrospectively classified all deaths among 39,272 patients enrolled in 13 HIV-1 cohorts (154,667 person years of follow-up) into the categories specified in the Cause of Death (CoDe) project protocol. In 1597 (85%) of 1876 deaths, a definitive cause of death could be assigned. Among these, 792 deaths (49.5%) were AIDS related, followed by non-AIDS malignancies (189; 11.8%), non-AIDS infections (131; 8.2%), violence- and/or drug-related causes (124; 7.7%), liver disease (113; 7.0%), and cardiovascular disease (103; 6.5%). Rates of AIDS-related death (hazard ratio [HR] per 100 cell decrease, 1.43; 95% confidence interval [CI], 1.34-1.53) and death from renal failure (HR, 1.73; 95% CI, 1.18-2.55) were strongly inversely related to CD4 count at initiation of ART, whereas rates of death attributable to AIDS (HR for viral load >5 vs 5 log copies/mL, 1.31; 95% CI, 1.12-1.53), infection (HR, 1.85; 95% CI, 1.25-2.73), cardiovascular (HR, 1.54; 95% CI, 1.05-2.27), and respiratory causes (HR, 3.62; 95% CI, 1.30-10.09) were higher in patients with baseline viral load >5 log copies/mL than in other patients. Rates of each cause of death were higher in patients with presumed transmission via injection drug use than in other patients, with marked increases in rates of liver-related (HR for injection drug use vs non-injection drug use, 6.06; 95% CI, 4.03-9.09) and respiratory tract-related (HR, 4.94; 95% CI, 1.96-12.45) mortality. The proportion of deaths classified as AIDS related decreased with increasing duration of ART. Important contributors to non-AIDS mortality in treated HIV-1-infected individuals must be addressed if decreases in mortality rates are to continue.
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          Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

          The distribution of risk factors for cardiovascular disease in patients aged 35-44 years who were treated for human immunodeficiency virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease inhibitor-containing regimen (n=223), compared with HIV-1-uninfected men (n=527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level, a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR], 1.20) and women (RR, 1.59; P<10(-6) for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy, risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered for all patients who have them.
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            Author and article information

            Affiliations
            [1 ]ISNI 0000 0000 9120 6856, GRID grid.416651.1, Centro Operativo AIDS, , Istituto Superiore di Sanità, ; via Regina Elena 299, 00161 Rome, Italy
            [2 ]ISNI 0000 0004 1757 9741, GRID grid.418321.d, Unit of Cancer Epidemiology, , Centro di Riferimento Oncologico di Aviano, IRCCS, ; via Gallini 2, 33081 Aviano, PN Italy
            [3 ]ISNI 0000 0001 2154 1445, GRID grid.425381.9, Integrated system for health, social assistance, welfare and justice, , Istituto Nazionale di Statistica, ; viale Liegi 13, 00198 Rome, Italy
            [4 ]ISNI 0000 0004 1757 9741, GRID grid.418321.d, Scientific Directorate, , Centro di Riferimento Oncologico di Aviano, IRCCS, ; via Gallini 2, 33081 Aviano, PN Italy
            Contributors
            barbara.suligoi@iss.it
            saverio.virdone@gmail.com
            mtaborelli@cro.it
            frova@istat.it
            grande@istat.it
            frgrippo@istat.it
            pappagal@istat.it
            vincenza.regine@iss.it
            lucia.pugliese@iss.it
            serrainod@cro.it
            zucchetto.epi@cro.it
            Journal
            BMC Infect Dis
            BMC Infect. Dis
            BMC Infectious Diseases
            BioMed Central (London )
            1471-2334
            28 August 2018
            28 August 2018
            2018
            : 18
            30153797
            6114052
            3336
            10.1186/s12879-018-3336-x
            © The Author(s). 2018

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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            © The Author(s) 2018

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