BACKGROUND:: Hepatitis delta virus (HDV) infection results in the most aggressive form of chronic viral hepatitis. There is scarce information about the prevalence, epidemiology, virological profile and natural historyof hepatitis delta in HIV patients. METHODS:: From 16,597 HIV patients enrolled in EuroSIDA, 1319 (7.9%) have ever reported serum HBsAg+. At last follow-up, 1084 (6.5%) patients wereHBsAg+. The HDV substudy was carried out on 422 individuals for whom stored sera were available at the time they were HBsAg+. Anti-HDV IgG was assessed using a commercial EIA and serum HDV-RNA was quantified using a real-time PCR method. RESULTS:: A total of 61/422 HBsAg+ carriers were anti-HDV+ (prevalence: 14.5%). Hepatitis delta predominated in intravenous drug users and for this reason in South and/or East Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV+ patients, with a median titer of 1.76x10¿copies/ml. Overall, delta hepatitis patients showed lower serum HBV-DNA than the rest of HBsAg+ carriers, although the inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D patients.Whereas HDV was not associated with progression to AIDS, it significantly influenced the risk of death. CONCLUSIONS:: The prevalence of anti-HDV in chronic HBsAg+/HIV carriers in EuroSIDA is 14.5%. Most of these patients exhibit detectable HDV viremia. Viral interference between HBV and HDV is manifest in all but HBV genotype D carriers, in whom overt co-replication of both virusesoccurs, which might result in enhanced liver damage.Overall, delta hepatitis increases the risk of liver-related deaths and overall mortality in HIV patients.