Risk of non-AIDS-defining events among HIV-infected patients not yet on antiretroviral therapy†

OBJECTIVES: Certain non-AIDS-related diseases have been associated with immunodeficiency and HIV RNA levels in HIV-infected patients on combination antiretroviral therapy (cART). We aimed to investigate these associations in patients not yet on cART, when potential antiretroviral-drug-related effects are absent and variation in RNA levels is greater. METHODS: Associations between, on the one hand, time-updated CD4 counts and plasma HIV RNA and, on the other hand, a composite non-AIDS-related endpoint, including major cardiovascular diseases, liver fibrosis/cirrhosis, and non-AIDS-related malignancies, were studied with multivariate Poisson regression models in 12 800 patients diagnosed with HIV infection from 1998 onwards while not yet treated with cART. RESULTS: During 18 646 person-years of follow-up, 203 non-AIDS-related events occurred. Compared with a CD4 count >/= 500 cells/muL, adjusted relative risks (RRs) for the composite endpoint were 4.71 [95% confidence interval (CI) 2.98-7.45] for a CD4 count < 200 cells/muL, 2.06 (95% CI 1.38-3.06) for a CD4 count of 200-349 cells/muL, and 1.19 (95% CI 0.82-1.74) for a CD4 count of 350-499 cells/muL. There was no evidence for an independent association with HIV RNA. Other important covariates were age [RR 1.40 (95% CI 1.31-1.49) per 5 years older], hepatitis B virus coinfection [RR 5.66 (95% CI 3.87-8.28)] and hepatitis C virus coinfection [RR 9.26 (95% CI 6.04-14.2)]. CONCLUSIONS: In persons not yet receiving cART, a more severe degree of immunodeficiency rather than higher HIV RNA levels appears to be associated with an increased risk of our composite non-AIDS-related endpoint. Larger studies are needed to address these associations for individual non-AIDS-related events.