Serious Non-AIDS events: Immunopathogenesis and interventional strategies

Denise C Hsu, Irini Sereti, Jintanat Ananworanich, Denise C Hsu, Irini Sereti, Jintanat Ananworanich

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.

Figures

Figure 1
Figure 1
Pathogenesis of serious non-AIDS events. HIV infection causes progressive decline in CD4 T cells through direct cytopathic effects and immune mediated killing of infected cells, as well as indirectly via immune activation. Other drivers of immune activation include co-infections and microbial translocation. HIV can contribute to organ dysfunction through detrimental effects on hepatic stellate cells and renal tubular cells. HIV may also be oncogenic. Co-infection with HBV and HCV is especially important in liver related events. In addition, patients’ underlying co-morbidities e.g. smoking, cardiovascular risk factors, and ART related toxicities also contribute to SNAEs.

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