While some of this excess mortality can be attributed to immunodeficiency, less than 20% of deaths in people followed in clinics ITF2357 for HIV are currently attributed to classical AIDS-related conditions [2]. Two large cohort collaborations have shown that, among those without advanced immunodeficiency, all-cause mortality is dominated by these non-AIDS-related conditions [3, 4], and that the CD4 cell count, which predicts risk of AIDS-associated morbidities, is also associated with the risk of death from non-AIDS-related causes; viral load may further refine this. The Strategies

for Management of Antiretroviral Therapy (SMART) trial found that interruption or deferral of antiretroviral therapy (ART) increased the risk of serious non-AIDS-related endpoints, principally a composite outcome HCS assay of cardiovascular events, kidney failure, decompensated liver cirrhosis and non-AIDS-related malignancies [5]. Serious non-AIDS-related events have been reported as elevated even with a high CD4 cell count (> 500 cells/μL), but it is unclear to what extent this is an independent association, or whether this association might be driven by known or unknown confounders. In a comparison of myocardial infarction (MI) rates between HIV-positive patients in the Kaiser Permanente programme in California and those presumed HIV uninfected the former had a statistically significant 1.4-fold greater risk of MI. Those with a current CD4 cell count of

> 500 cells/μL

who were on ART had no increased risk compared with the HIV-negative population, but there was a trend towards an increased risk among those not on ART [6]. In an observational cohort study of HIV-infected ART-naïve patients with high Dimethyl sulfoxide CD4 cell counts (> 350 cells/μL), death rates were raised compared with the general population. However, among men who have sex with men and who had a CD4 cell count of > 500 cells/μL, there was no evidence of increased risk of death compared with the general population [7]. In the COHERE Collaboration of Observational HIV Epidemiological Research Europe collaboration of European observational studies, men who have sex with men and who had a current CD4 cell count of > 500 cells/μL had no increased risk of death compared with the general population. However, those with previous AIDS disease had an increased risk of death, even when the current CD4 cell count was > 500 cells/μL [8]. Projections modelled on these studies suggest that, for a man infected with HIV in 2010 aged 30 years who is diagnosed early and who adheres to continuous ART, the median age at death is 75 years. The average loss of 7 to 10 years attributable to HIV infection is comparable to the effect of diabetes or cigarette smoking in the general population [9, 10]. Those with optimum adherence may well have an even higher life expectancy than this, but the ongoing risks in people with viral suppression and a high CD4 cell count are unknown.