No abstract

Antiretroviral therapy has been a spectacular success. People are now asking if the end of AIDS is possible. For those who are motivated to take therapy and who have access to lifelong treatment, AIDS-related illnesses are no longer the primary threat, but a new set of HIV-associated complications have emerged, resulting in a novel chronic disease that for many will span several decades of life. Treatment does not fully restore immune health; as a consequence, a number of inflammation-associated and/or immunodeficiency complications such as cardiovascular disease and cancer are increasing in importance. Cumulative toxicities from exposure to antiretroviral drugs for decades cause clinically-relevant metabolic disturbances and end-organ damage. There are growing concerns that the multi-morbidity associated with HIV disease may impact healthy aging and could overwhelm some health care systems, particularly those in resource-limited regions that have yet to fully develop a chronic care model. Given the problems inherent in treating and caring for a chronic disease that might persist for several decades, a global effort to identify a cure is now underway.

Although antiretroviral therapy for HIV infection prevents AIDS related complications and prolongs life, it does not fully restore health. Long-term treated patients remain at higher than expect risk for a number of complications typically associated with aging, including cardiovascular disease, cancer, osteoporosis and other end-organ diseases. The potential effect of HIV on health is perhaps most clearly exhibited by a number of immunologic abnormalities that persist despite effect suppression of HIV replication. These changes are consistent with some of the changes to the adaptive immune system that are seen in the very old (“immunosenescence”) and that are likely related in part to persistent inflammation. HIV-associated inflammation and immunosenescence have been implicated as causally related to the premature onset of other end organ diseases. Novel therapeutic strategies aimed at preventing or reversing these immunologic defects may be necessary if HIV infected patients are achieve normal life span.

sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.