Absence of anti-HBc in HIV/HBV coinfected individuals with advanced immunosuppression

Abstract

HBV chronic infection is frequent among HIV carriers but serological markers may present atypical profiles among these patients. HBsAg reactivity in anti-HBc negative patients is a rare event that has been described in HIV co-infected patients. This pattern was related to mutations in the coding region of the viral core protein, to aberrant host immune response or to both factors. The aim of this study was to evaluate the occurrence of anti-HBc negative/HBsAg positive profile in HIV/HBV coinfected patients and to identify possible associations with clinical variables and HBV mutations. This is a case control study based in medical reports and laboratorial records from the studied patients. For each anti-HBc negative/HBsAg positive identified case, 2 anti-HBc positive/HBsAg positive controls matched by sex and age were selected. HBVDNA was detected by real time PCR. Patients with detectable viral load were further analyzed by amplification and sequencing of precore/core and S regions for genotyping and identification of mutations possibly involved with this anomalous serological pattern. Our study population was selected from 2412 anti-HIV positive patients. Among them, 120 were HBsAg reactive. Patients were followed up for a mean time of 5 years, utilizing from 1 to 5 samples for serological evaluations. We identified 12 patients (11 male and one female) who were negative for anti-HBc but positive for HBsAg in at least one sample during follow up, Compared with controls, anti-HBc negative / HBsAg positive cases had lower mean count of CD4 + T lymphocytes (349.2 vs. 455 cells/mm3, P = 0.048). There was no correlation between anti-HBc negative/HBsAg positive serological profile and the analyzed clinical variables (time of diagnosis, history of opportunistic infections, nadir CD4 + T cells, use of medications effective against HBV or advanced liver disease). Serum samples from 7 patients were submitted to the HBV viral load detection and HBV DNA was detected in only 3 of these patients, with a mean viral load of 5.67 log. These three cases were infected by HBV subgenotype A1 and the analysis of the precore/core region of these viruses did not identify any mutation that could explain the anomalous serological profile. In our series of HBV/HIV co-infected patients, 10% of them were concomitantly HBsAg reactive but anti-HBc nonreactive. No mutation in the precore/core regions was identified that could explain this profile. As these patients showed a lower mean CD4+T cells count compared to the control group, our findings may suggest that advanced immunosuppression may be involved, determining the loss of anti-HBc at least in detectable levels.