ArticlesTrends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration
Introduction
In settings with access to antiretroviral therapy (ART), AIDS-related mortality in HIV-positive individuals in care has decreased substantially, with life expectancy now approaching that seen in the general population.1, 2, 3 As a result, the relative importance of other traditionally non-AIDS-related morbidities has increased, and a wider range of complications has been seen than in previous years.1
The occurrence of some non-AIDS-related morbidities might be higher in people with HIV than in the general population for three main reasons. First, the HIV-positive population in high-income settings has a high level of traditional risk factors for non-AIDS morbidities, such as smoking and hepatitis co-infection.4, 5, 6 Second, available evidence suggests that the persistent immunodeficiency, immune dysregulation, immune activation, and inflammation associated with HIV infection, including in patients on ART, might increase the risk of some of these morbidities.7, 8 Third, antiretroviral-related adverse events such as dyslipidaemia and diabetes might also play a part. Although ART has clear benefits, lifelong exposure to these drugs is likely to be needed. Thus, long-term surveillance for emerging or not-yet-identified serious adverse events caused by extended exposure to these novel agents is important. The reporting of such events using a passive, clinician-initiated approach will probably not be sensitive enough to detect emerging issues should they occur. A major aim of the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study is to identify whether emerging serious toxicities are linked with use of ART by looking for increases in the rates of mortality either from a particular organ system, from cancers, or from other as-yet unanticipated causes.
We aimed to investigate trends over time in all-cause mortality and for specific causes of death from 1999 to 2011 within the D:A:D study. We examined whether any recorded changes over time in death rates (overall and cause-specific) could be explained by changes in the characteristics of the HIV-positive population, including HIV immunological and virological status. Finally, we assessed whether any unexpected increases in rates of death from any specific cause emerged.
Section snippets
Study design
Participants included were from the D:A:D study,9 a collaboration of 11 (nine ongoing) cohort studies of 49 731 individuals with HIV-1 receiving care at 212 clinics in Europe, USA, and Australia. All participants were under active follow-up in their cohorts at the time of enrolment. Prospective follow-up, with visits of at least every 8 months, began in January, 1999, irrespective of ART status. Participants were recruited during three recruitment waves: December, 1999–April, 2001; December,
Results
Most of the 49 731 D:A:D study participants were men, the most common mode of HIV acquisition was sex between men, and the median age at study entry was 38 years (table 1). Compared with participants who were being followed up on Jan 1, 2001 (when the first wave of recruitment was nearing completion), those who were being followed up in 2011 were less likely to have acquired HIV through intravenous drug use, less likely to be hepatitis B virus-positive or hepatitis C virus-positive, less likely
Discussion
Our findings suggest that death rates in HIV-positive individuals with access to care and antiretroviral therapy have decreased since 1999–2000. We can detect no indication of an increase in risk of death from any specific cause as a potential result of long-term adverse effects of ART, and the risk of death from other causes—ie, those other than AIDS-related disease, cardiovascular disease, liver disease, and non-AIDS cancers—is low. These findings provide further evidence of the substantial
References (35)
- et al.
Addressing smoking during medical visits: patients with immunodeficiency virus
Am J Prev Med
(2012) - et al.
Treatment of hepatitis C in patients infected with human immunodeficiency virus in the direct-acting antiviral era
Infect Dis Clin North Am
(2012) - et al.
Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study
HIV Med
(2013) Int J Epidemiol
(2012)- et al.
Projected life expectancy of people with HIV according to timing of diagnosis
AIDS
(2012) - et al.
Cardiovascular disease risk factors in HIV patients – association with antiretroviral therapy. Results from the DAD study
AIDS
(2003) - et al.
Disparities in prevalence of key chronic disease by gender and race/ethnicity among antiretroviral-treated HIV-infected adults in the US
Antivir Ther
(2012) - et al.
HIV and aging: State of knowledge and areas of critical need for research. A report to the NIH Office of AIDS Research by the HIV and Aging Working Group
J Acquir Immune Defic Syndr
(2012) - et al.
The role of HIV in serious diseases other than AIDS
AIDS
(2008) - et al.
Inflammatory and coagulation biomarkers and mortality in patients with HIV infection
PLoS Med
(2008)
Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multicohort collaboration
Lancet
The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology
Epidemiology
Technical briefing 3: commonly used public health statistics and their confidence intervals
Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study
AIDS
Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls
BMJ
Causes of death among Danish HIV patients compared with population controls in the period 1995–2008
Infection
Mortality due to cancer among people with AIDS: a novel approach using registry-linkage data and population attributable risk methods
AIDS
Cited by (746)
Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV
2024, Enfermedades Infecciosas y Microbiologia Clinica