Background: Now that the main beneficial impact of HAART at the population level has been described the attention of epidemiologists in this second decade of the HAART era has turned to quantifying and understanding the causes of the residual excess disease and death that remains. This residual clinical burden is due to multiple factors. Much of the remaining AIDS conditions observed can be attributed to late diagnosis of HIV, but failure to retain in care all of those diagnosed, and chronically poor adherence in some individuals who are retained in care are probably also significant factors. With the recent introduction of several new antiretroviral drugs, the exhaustion of drug options due to presence of multi-drug resistance is probably currently responsible for a relatively low proportion of new AIDS events and deaths. However, AIDS diseases may not be the only clinical problem that HIV is causing. Several strands of evidence suggest HIV could impact on the risk of an array of other serious conditions, including diseases of the liver, kidney, cardiovascular system, and non-AIDS malignancies. The discussion will consist of an informal review of recent published and some unpublished literature relating to these issues, principally focusing on the evidence for HIV being linked to the serious non-AIDS diseases outlined above. Sources of evidence to examine this possible link include:  comparison of risk of such events between HIV-infected and HIV-uninfected people, the association between CD4 count and risk of serious non-AIDS events, and a randomized trial of the influence on serious non-AIDS events of reduction of HIV RNA level with ART..

Conclusions: Data from all these sources have their limitations but taken together evidence for a link between HIV and risk of serious non-AIDS diseases is appreciable. Possible approaches to further reducing the clinical burden will then be outlined, including the potential need to consider earlier ART initiation. It is important to better understand the epidemiology of residual HIV-associated disease in the HAART era so that suitable potential new interventions can be designed.