Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis

Abstract

The advent of antiretroviral therapy has significantly improved AIDS-related morbidity and mortality. Yet, among people living with HIV, deaths due to non-AIDS-defining illnesses have been on the rise. The objective of this study was to provide information about the global prevalence and distribution of non-AIDS causes of death in the last ten years among people living with HIV receiving antiretroviral therapy, by income levels of countries. We used broad search terms in Google Scholar, PubMed, and EMBASE to identify all studies that investigated the cause of death among people living with HIV receiving antiretroviral therapy, published after January 1, 2005. References were also identified from review articles and reference lists. Inclusion criteria were English language, the study's end date was after 2005, all patients were HIV-positive, at least two-thirds of the patients were receiving antiretroviral therapy, at least one patient died of non-AIDS causes of death. Titles, abstracts, and articles were reviewed by at least two independent readers. Of 2951 titles identified in our original search, 151 articles were selected for further screening. We identified 19 studies meeting our full criteria, with patients from 55 different nations. Pooled non-AIDS causes of death prevalence estimates in high-income countries were 53.0% (95% confidence interval, 43.6-62.3), in developing countries 34.0% (95% confidence interval, 20.3-49.1), and in sub-Saharan countries 18.5% (95% confidence interval, 13.8-23.7). Statistically significant variation was noted within and between categories. Our findings show that a significant number of people living with HIV across the world die from cardiovascular disease, non-AIDS malignancies, and liver disease. There is a global need for further scrutiny in all regions to improve preventive measures and early detection according to distinct causes of death patterns.

Increased non‐AIDS mortality among persons with AIDS‐defining events after antiretroviral therapy initiation

“…Over 60% of the coded causes of death in ART-CC were due to NADEs. This is consistent with the findings from a recent systematic review and meta-analysis which estimated the pooled proportion of patients with death due to NADEs in high-income countries during the ART era was 54% (95% CI 46% to 62%) [37]. The most frequent cause of NADE death in our study was non-AIDS malignancies (24%) followed by accidents/suicides/overdoses (17%), cardiovascular deaths (16%), non-AIDS infections (15%) and hepatic deaths (13%).…”

“…Overall, the crude mortality rate per 1000 p‐y due to NADEs (5.26 (95% CI 5.09 to 5.42)) was slightly higher than that reported from other cohorts in high‐income countries, including South Korea (3.71, 95% CI 2.52 to 5.48) 35, Spain (3.75, 95% CI 2.84 to 4.94) 36, and from the Data collection on Adverse Events of anti‐HIV Drugs (D:A:D) cohort in Australia, Europe, and the United States (4.28, 95% CI 4.06 to 4.53) 12, 37–the latter two have some overlap with our dataset. It is possible this finding is related to differences in baseline CD4+ count (342 cells/mm 3 (IQR 163 to 546) in Spain, 400 (IQR 242 to 590) in D:A:D, and 244 (IQR 116 to 369) for ART‐CC, respectively) as several previous studies have described lower CD4+ counts as risk factors for NADE mortality 13, 14.…”

Coronary Artery Disease in HIV-Infected Patients: Downside of Living Longer

“…Thus, people living with HIV (PLWH) now live long enough to face conditions that were traditionally seen in the elderly, such as cardiovascular disease (CVD) [4]. In high-income countries, CVD is the second non-AIDS cause of death in people living with HIV infection, and it is a significant contributor to non-AIDS deaths in developing and sub-Saharan countries [5–7]. Studies have shown that HIV-infected individuals are at higher risk of several cardiovascular abnormalities, such as coronary artery disease (CAD) [8, 9], heart failure and heart failure admission [10], subclinical atherosclerosis of coronary [11–13] and carotid arteries [8, 14, 15], global and regional left ventricular (LV) systolic function [16], LV diastolic dysfunction [16, 17], myocardial fibrosis and steatosis [9, 18], pulmonary hypertension [19], stroke [20], atrial fibrillation [21], and sudden cardiac death [22].…”

Cardiorespiratory fitness levels and moderators in people with HIV: A systematic review and meta-analysis

“…People living with HIV (PLWH) have higher levels of morbidity and mortality than the general population (Farahani et al, 2016). The non-AIDS related mortality rates are largely attributable to cardiovascular disease (Farahani et al, 2016).…”

“…The non-AIDS related mortality rates are largely attributable to cardiovascular disease (Farahani et al, 2016). Current hypotheses link the increased incidence of these comorbidities to side-effects of antiviral therapy (Dillon et al, 2013;El-Sadr, 2007), HIV-related chronic inflammation (Hearps et al, 2014) and modifiable lifestyle factors, such as increased tobacco use (Lifson and Lando, 2012) and decreased physical activity (Schuelter-Trevisol et al, 2012).…”