Serious Non-AIDS events: Immunopathogenesis and interventional strategies

Denise C Hsu,Irini Sereti,Jintanat Ananworanich

doi:10.1186/1742-6405-10-29

Abstract

Despite the major advances in the management of HIV infection, HIV-infected patients still have greater morbidity and mortality than the general population. Serious non-AIDS events (SNAEs), including non-AIDS malignancies, cardiovascular events, renal and hepatic disease, bone disorders and neurocognitive impairment, have become the major causes of morbidity and mortality in the antiretroviral therapy (ART) era. SNAEs occur at the rate of 1 to 2 per 100 person-years of follow-up. The pathogenesis of SNAEs is multifactorial and includes the direct effect of HIV and associated immunodeficiency, underlying co-infections and co-morbidities, immune activation with associated inflammation and coagulopathy as well as ART toxicities. A number of novel strategies such as ART intensification, treatment of co-infection, the use of anti-inflammatory drugs and agents that reduce microbial translocation are currently being examined for their potential effects in reducing immune activation and SNAEs. However, currently, initiation of ART before advanced immunodeficiency, smoking cessation, optimisation of cardiovascular risk factors and treatment of HCV infection are most strongly linked with reduced risk of SNAEs or mortality. Clinicians should therefore focus their attention on addressing these issues prior to the availability of further data.

Highlights

Since the first description of AIDS in 1981, there have been tremendous advances in understanding the biology of the virus, the host’s immune response and the clinical management of HIV infection
Despite the use of antiretroviral therapy (ART), HIV-infected patients still have higher mortality and morbidity when compared to the general population
Serious non-AIDS events (SNAEs) occur at the rate of about 1-2 per 100 person-years of follow-up (PYFU) and are the predominant causes of morbidity and mortality in HIV-infected patients in the ART era

Summary

Introduction

Since the first description of AIDS in 1981, there have been tremendous advances in understanding the biology of the virus, the host’s immune response and the clinical management of HIV infection. In HIV-infected patients, CRP, IL-6 and D-dimer levels [61] as well as markers of T cell activation [50,87] remain higher than uninfected controls despite suppressive ART. Some studies have noted a reduction in D-dimer levels [168], T cell activation [165,166,169] as well as an early transient increase in 2-LTR circles post raltegravir intensification [168,170], suggesting that residual viraemia was occurring prior to raltegravir intensification and was contributing to immune activation in some patients. A non-randomized study of HCQ in 20 ART-treated patients showed decline in plasma LPS, IL-6 and reduced T cell and monocyte activation [193]. A retrospective cohort study on both ART-treated and untreated HIV-infected patients found that probiotic yogurt consumption was associated with a greater increase in CD4 T cell count even after adjustment for ART [211]. A trial using mesalamine in ART treated, virologically suppressed patients with CD4 T cell count

Conclusions

Findings

72. Ross R