Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study

doi:10.1016/S2352-3018(15)00077-6

The Lancet HIV

Volume 2, Issue 7, July 2015, Pages e288-e298

https://doi.org/10.1016/S2352-3018(15)00077-6 Get rights and content

Summary

Background

Whether the reported high risk of age-related diseases in HIV-infected people is caused by biological ageing or HIV-associated risk factors such as chronic immune activation and low-grade inflammation is unknown. We assessed time trends in age-standardised and relative risks of nine serious age-related diseases in a nationwide cohort study of HIV-infected individuals and population controls.

Methods

We identified all HIV-infected individuals in the Danish HIV Cohort Study who had received HIV care in Denmark between Jan 1, 1995, and June 1, 2014. Population controls were identified from the Danish Civil Registration System and individually matched in a ratio of nine to one to the HIV-infected individuals for year of birth, sex, and date of study inclusion. Individuals were included in the study if they had a Danish personal identification number, were aged 16 years or older, and were living in Denmark at the time of study inclusion. Data for study outcomes were obtained from the Danish National Hospital Registry and the Danish National Registry of Causes of Death and were cardiovascular diseases (myocardial infarction and stroke), cancers (virus associated, smoking related, and other), severe neurocognitive disease, chronic kidney disease, chronic liver disease, and osteoporotic fractures. We calculated excess and age-standardised incidence rates and adjusted incidence rate ratios of outcomes for time after HIV diagnosis, highly active antiretroviral therapy (ART) initiation, and calendar time. The regression analyses were adjusted for age, sex, calendar time, and origin.

Findings

We identified 5897 HIV-infected individuals and 53 073 population controls; median age was 36·8 years (IQR 30·6–44·4), and 76% were men in both cohorts. Dependent on disease, the HIV cohort had 55 050–57 631 person-years of follow-up and the population controls had 638 204–659 237 person-years of follow-up. Compared with the population controls, people with HIV had high excess and relative risk of all age-related diseases except other cancers. Overall, the age-standardised and relative risks of cardiovascular diseases, cancers, and severe neurocognitive disease did not increase substantially with time after HIV diagnosis or ART initiation. Except for chronic kidney diseases, the age-standardised and relative risks of age-related diseases did not increase with calendar time.

Interpretations

Severe age-related diseases are highly prevalent in people with HIV, and continued attention and strategies for risk reduction are needed. The findings from our study do not suggest that accelerated ageing is a major problem in the HIV-infected population.

Funding

Preben og Anna Simonsens Fond, Novo Nordisk Foundation, Danish AIDS Foundation, Augustinus Foundation, and Odense University Hospitals Frie Fonds Midler.

Introduction

HIV-infected individuals are at increased risk of several age-related diseases including myocardial infarction,¹ stroke,² some non-AIDS associated cancers,³ severe neurocognitive disease,⁴ chronic kidney disease,⁵ chronic liver disease,⁶ and osteoporotic fractures.⁷ Despite the protective effects of highly active antiretroviral therapy (ART), HIV might have a detrimental effect on the risk of these diseases partly as a result of HIV-induced chronic immune activation, persistent low-grade inflammation, and potentially accelerated ageing.⁸ Consequently, risks of severe age-related diseases might increase not only with age, but also with duration of HIV and ART, and with later calendar years independent of age.

In this study, we used a nationwide population-based cohort of HIV-infected individuals and a comparison cohort from the general population to estimate time trends in the risk of nine serious age-related diseases that are highly prevalent in people with HIV.

Section snippets

Study design and participants

As of Jan 1, 2014, Denmark had a population of 5·6 million, with an estimated HIV prevalence of 0·1% in adults. Treatment of HIV is restricted to eight specialised centres, in which patients are seen on an outpatient basis every 12–24 weeks. Health care in Denmark is tax-supported and antiretroviral treatment is provided free of charge. ART is prescribed according to national guidelines.⁹

The primary data source for our study was the Danish HIV Cohort Study (DHCS), which is a nationwide,

Results

6174 HIV-infected individuals met inclusion criteria; the proportion older than 50 years increased from 13% (276 of 2202) in 1995 to 43% (1791 of 4190) in 2014 (figure 1). 277 HIV-infected individuals were excluded because of a diagnosis of age-related disease before the date of inclusion, leaving 5897 HIV-infected individuals and 53 073 controls in the study. The median age of the HIV-infected individuals and control cohorts was 36·8 years and 76% were men (table).

Depending on the disease

Discussion

In this study, we noted that age-standardised and relative risks of cardiovascular diseases, cancers, and severe neurocognitive disease in Danish HIV-infected individuals did not increase with time after HIV diagnosis or ART initiation. Although the age-standardised risk of chronic kidney disease increased with time after ART initiation, no substantial increase was noted with time after HIV diagnosis. The opposite was noted for risk of chronic liver disease, whereas the age-standardised and

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ArticlesTime trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study

Summary

Background

Methods

Findings

Interpretations

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

Lancet

Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study

Clin Infect Dis

Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study

AIDS

Risk of cancer among HIV-infected individuals compared to the background population: impact of smoking and HIV

AIDS

Incidence and impact on mortality of severe neurocognitive disorders in persons with and without HIV infection: a Danish nationwide cohort study

Clin Infect Dis

Increased risk of dialysis and end-stage renal disease among HIV patients in Denmark compared with the background population

Nephrol Dial Transplant

Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study

Arch Intern Med

Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study

AIDS

HIV infection, inflammation, immunosenescence, and aging

Annu Rev Med

Cohort profile update: the Danish HIV Cohort Study (DHCS)

Int J Epidemiol

Historical epidemiology of hepatitis C virus (HCV) in selected countries

J Viral Hepat

Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection

J Infect Dis

Inflammation, coagulation and cardiovascular disease in HIV-infected individuals

PLoS One

Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial

Antivir Ther

Articles
Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study