Abstract
ObjectivesPersistent hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in sub-Saharan Africa. The HIV epidemic has the potential to affect its biology. Immunisation protocols established in the pre-HIV era are based upon data showing predominantly horizontal infant transmission. This study aimed to determine whether HIV co-infection will change the epidemiology of HBV both by increasing infectivity and by favouring the escape of viruses bearing phenotypically altered HBsAg. MethodsThis retrospective cross-sectional study used antenatal samples from the 2008 Antenatal Sentinel HIV and Syphilis Prevalence Survey in the Western Cape, South Africa. All HIV-infected women were age and race-matched to HIV-uninfected women. Samples were tested for serological markers of HBV and HDV infection. HBV viral load, consensus sequencing and genotyping were performed. Luminex technology was used to determine HBsAg phenotype. All samples from HIV-infected women were tested for traces of antiretroviral drugs by mass spectrometry. ResultsThis study showed a trend toward loss of immune control of HBV in HIV-infected women with 3.4% of samples containing HBsAg, 18.9% contained HBeAg. In contrast, 2.9% of samples from HIV-uninfected women contained HBsAg and 17.1% of these HBeAg. The median HBV load in the HIV-infected group was 9.72×107IU/ml and in the HIV-uninfected group 1.19×106IU/ml. Genotyping showed 63/68 samples belonged to genotype A and the remainder genotype D. Mutations in the precore region were found in 35% and 33% of samples from HIV-infected and HIV-uninfected respectively. Although no major epitope ablation was found, marked variation in HBsAg profiles in HIV-infected group was demonstrated. No HDV infection was detected. ConclusionHIV-HBV co-infected women exhibit a degree of immune escape. One in six HBV-infected pregnant women, irrespective of HIV status is HBeAg seropositive. HBV immunization of newborns in sub-Saharan Africa should be implemented.
Highlights
A significant association was found between HBV surface antigen (HBsAg) seropositivity and a lower educational grade (p = 0.03), but not between HBsAg status and human immunodeficiency virus (HIV) status (p = 0.404), age (p = 0.52) or parity (p = 0.27)
Unlike data from well-resourced countries which show a significant difference in HBsAg prevalence in HIV-infected compared to uninfected persons [16], this study confirms previous antenatal data from Africa showing little difference in the prevalence of HBsAg in HIV-infected compared with HIV-uninfected women, as found elsewhere in South Africa, Côte D’Ivoire, Malawi and Tanzania [17,18,19,20]
Median 25%-75% Range immune control in HIV co-infected women who demonstrated a trend towards higher hepatitis B virus (HBV) viral loads. In this antenatal population from the Western Cape, as many as one in six (18.1%) of HBV-infected mothers are HBV e antigen (HBeAg)-seropositive and anti-HBe negative, irrespective of HIV status. This is a higher proportion than expected and contrasts with Oshitani and colleagues who found a difference in HBeAg prevalence in HIVinfected compared with HIV-uninfected women (25% vs. 12.3%) [21]
Summary
Chronic hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in sub-Saharan Africa (SSA) [1] despite. Various parameters of HBV infection are altered by the immunosuppression caused by human immunodeficiency virus (HIV) infection. Those persons co-infected have a greater prevalence of HBV e antigen (HBeAg) which is a marker for infectivity [2], higher HBV DNA levels [3], more frequent HBV reactivation [4] and a higher prevalence of occult HBV infection [5]. Two resulting aspects of particular concern are higher infectivity facilitating HBV onward transmission and the potential for generation of immune escape variants during reactivation.
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