Hepatitis B virus infection in human immunodeficiency virus infected southern African adults: occult or overt--that is the question

Abstract

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART)-naïve HIV(+ve) adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR) of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5%) showed at least one HBV marker, with 53.7% HBV DNA(-ve) (resolved) and 23.8% HBV DNA(+ve) (current) [8.7% HBsAg(+ve): 15.1% HBsAg(-ve)]. Only the total number of sexual partners distinguished HBV DNA(+ve) and HBV DNA(-ve) participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg(-ve) HBV DNA(+ve) participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg(-ve) HBV DNA(+ve) participants did not differ from HBsAg(+ve) HBV DNA(+ve) (overt) participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV(+ve) participants were HBV DNA(+ve), of which the majority were HBsAg(-ve) and were only detected using nucleic acid testing. Detection of HBsAg(-ve) HBV DNA(+ve) subjects is advisable considering they were clinically indistinguishable from HBsAg(+ve) HBV DNA(+ve) individuals and should not be overlooked, especially if lamivudine is included in the ART.

Figure 1. Serological and DNA markers for HBV detected in 71 of 298 HIV^+ve participants.

Overt refers to HBsAg^+ve and “occult” to HBsAg^−ve. According to the Taormina definition, false occult infections are HBsAg^−ve with HBV viral load (VL) ≥200 IU ml⁻¹ and true occult infections are HBsAg^−ve with HBV VL <200 IU ml⁻¹ .

Figure 2. Box and whisker plot of HBV viral loads of the 71 HBV DNA^+ve participants separated into the six serological groups (A to F), interpreted according to Hollinger (2008) with modifications .

“n” indicates the number of participants in each group. ALT and CD4 cell counts for each group are indicated in the table below the plot as “Median (Interquartile Range)”. Viral loads and CD4 cell counts did not differ significantly between the six serological groups. The five HBeAg^+ve participants belonged to serological group C.