Occult hepatitis B virus (HBV) is defined by the presence of plasma HBV DNA in individuals with HBV core antibodies (anti-HBc), but without HBV surface antigen (HBsAg). The prevalence of occult HBV in HIV-infected patients remains controversial, and the risk factors, clinical significance and effect of highly active antiretroviral therapy (HAART) are unknown. The aim of this study was to determine prevalence, risk factors, and clinical significance of occult HBV in HIV-infected patients and to evaluate the effect of HAART. Plasma HBV DNA levels were determined in 191 HIV positive, antiretroviral naïve patients, who were anti-HBc positive and HBsAg negative. Quantitative HBV DNA was determined using a Taqman real-time nested PCR. Additionally, plasma HIV RNA levels, CD4 cell counts, anti-HBs-antibodies, anti-HCV-antibodies, ALT, AST, and gammaGT were determined. Occult HBV (a plasma HBV DNA level >50 copies/ml) was detected in 9/191 (4.7%) of the patients. Among 45 anti-HBs-negative patients (isolated anti-HBc positive), the prevalence was 11.1%. Patients with occult HBV had significantly lower CD4 count compared to anti-HBc-positive/HBsAg negative/HBV DNA-negative patients (105 +/- 157 (median +/- SD) vs. 323 +/- 299 cells/mm(3), P = 0.019). When HAART (including lamivudine) was initiated in the patients with occult HBV, HBV DNA was no longer detectable in any of the patients during 3 years of follow-up. In conclusion, occult HBV was associated with low CD4 counts and may be viewed as opportunistic reactivation of HBV that resolves as a consequence of HAART induced immune reconstitution and/or the effect of lamivudine.