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

Abstract

Introduction HIV‐1 infection leads to chronic inflammation and to an increased risk of non‐AIDS mortality. Our objective was to determine whether AIDS‐defining events (ADEs) were associated with increased overall and cause‐specific non‐AIDS related mortality after antiretroviral therapy (ART) initiation.MethodsWe included HIV treatment‐naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART‐CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause‐specific non‐AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non‐Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.ResultsThe adjusted hazard of overall non‐AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause‐specific non‐AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause‐specific non‐AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).ConclusionsIn this large multi‐centre cohort collaboration with standardized assignment of causes of death, non‐AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non‐AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Effect of AIDS-defining events at initiation of antiretroviral therapy on long-term mortality of HIV/AIDS patients in southwestern China: a cohort study

“…In our study, the prevalence of ADE in HIV/AIDS patients at ART initiation was 16.86%, which is roughly consistent with the data of previous studies in other countries or regions; for example, a report from Japan showed that 29.4% of patients with newly diagnosed HIV were ADE [29] . Our study also showed that even when individuals were on ART, the mortality of patients with ADE was significantly higher than that of those without ADE, which is consistent with a previous study [30] . In our study, disseminated mycosis, recurrent severe bacterial pneumonia, herpes zoster, extrapulmonary tuberculosis, and candidiasis of the oesophagus were the top causes of death by ADE.…”

Effect of AIDS-defining events at initiation of antiretroviral therapy on long-term mortality of HIV/AIDS patients in Southwestern China: a retrospective cohort study

“…In this study, the prevalence of ADE in HIV/AIDS patients at ART initiation was 16.86%, which was roughly consistent with the data of previous studies in other countries or regions; for example, a report from France showed that 16% of patients with newly diagnosed HIV were ADE [31]. Our study also showed that even when individuals were on ART, the mortality of patients with ADE was signi cantly higher than that of those without ADE, which was consistent with some previous studies: a large multi-centre cohort study showed that non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE [32], and this multiple is a little higher than that of this study; a research showed that HIV controllers experience non-ADE, albeit at lower rates than patients who do not spontaneously control the virus [33]. While in this study, disseminated mycosis, recurrent severe bacterial pneumonia, herpes zoster, extrapulmonary tuberculosis, and candidiasis of the oesophagus were the top causes of death by ADE.…”

Methods of competing risks flexible parametric modeling for estimation of the risk of the first disease among HIV infected men

“…Another important aspect of this study was investigating the occurrence of different types of events among HIV positive patients at the presence of each other. Recently, Pettit et.al [48]. showed that the risk of non-AIDS mortality among patients with an AIDS-defining event was twice higher than patients without an AIDS-defining event.…”