To know the prevalence, incidence and factors associated with hepatitis E virus (HEV) infection in HIV-infected individuals in Spain, as well as to provide information on the natural history of HIV/HEV coinfection.Prospective cohort study.Serum HEV IgG antibodies were tested in 613 HIV-infected patients at baseline and 2 years thereafter. Positive samples were tested for HEV-RNA. In patients with seroconversion, changes in liver function tests, serum HEV IgM antibodies and HEV RNA in samples collected between the baseline and the final time points were analyzed.One hundred and sixty-one (26%) patients tested positive for serum HEV IgG antibodies at baseline. HEV exposure was more common in men than in women (28 vs. 18%; P = 0.022) and increased linearly with age: 16, 26 and 44% in younger than 40, from 40 to 49 and older than 50 years, respectively (P = 0.000002). One patient bore the serum HEV-RNA at baseline. Eighteen (4%) HEV-seronegative patients seroconverted during the follow-up. None of the factors predicted seroconversion. One patient with seroconversion developed acute hepatitis and four mild hypertransaminasemia without another apparent cause. No case of seroconversion evolved to chronic HEV infection. Seroreversion was detected in 19% of the HEV-seropositive patients at baseline. Patients with seroreversion showed more commonly CD4 cell counts below 500 cells/μl than those who remained seropositive (77 vs. 46%; P = 0.004).Exposure to HEV among HIV-infected patients in Spain is very common, and this increases with age. Evolution to chronic infection is extremely unusual. Most cases of acute HEV infection seem to be clinically and biochemically unexpressive, therefore going unnoticed.
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