Prevalence and Profile of Hepatitis B Virus Infection among HIV-Infected Adults at Panzi Referral Hospital, in the Post-Conflict South Kivu Province, Eastern Democratic Republic of Congo

Background: Little is known about the prevalence of co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in the post-conflict South-Kivu Province, Eastern Democratic Republic of the Congo. Therefore, we aimed to determine such data at Panzi Referral Hospital. Methods: We conducted a cross-sectional study of 198 HIV-positive patients seen in consultation from June to 31 November 2017. Socio-demographic and clinical data were collected by interview and clinical examination. Blood sample was taken for serological analyses. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. CD4+ T cell counts were determined for all patients. Data analysis was done using the JMP 7.1 software. Proportions were compared using a Chi-square test or Fisher test. Results: Fourteen of 198 participants (7.07%, 95% confidence interval [CI]: 4.35 11.51) were HBsAg-positive. Overall, 33.33% of the subjects had been in contact with HBV and 36.87% were carriers of the immunization marker. How to cite this paper: Bisimwa, P.B., Masemo, D.B., Hamama, A.B.N., Mitima, T.K., Byabène, A.K., Shindano, T.A., Harlow, S., Mukonkole, J.P.M., Komas, N.P. and Nachega, J.B. (2019) Prevalence and Profile of Hepatitis B Virus Infection among HIV-Infected Adults at Panzi Referral Hospital, in the Post-Conflict South Kivu Province, Eastern Democratic Republic of Congo. World Journal of AIDS, 9, 105-117. https://doi.org/10.4236/wja.2019.93008 Received: June 12, 2019 Accepted: July 26, 2019 Published: July 29, 2019 P. B. Bisimwa et al. DOI: 10.4236/wja.2019.93008 106 World Journal of AIDS Among co-infected patients, 28.57% had a chronic replicative viral B infection, 57.14% a chronic non-replicative infection and 14.29% were inactive carriers. No patient had an acute infection. Co-infection was higher in participants who were aged 55 and over (8.3%), men (12.90%, p = 0.0306), married (12.00%, p = 0.0063), or of Lega ethnicity (14.3%, p = 0.0100). Some clinical signs such as hepatomegaly and jaundice (p < 0.0001), fever (p = 0.0095), splenomegaly (p = 0.0007), ascites (p = 0.0173) and viral encephalitis (p ≤ 0.0001) were associated with co-infection. Severe immunosuppression (50.00%, p = 0.0110) and WHO clinical stage III/IV (10.64%; p = 0.0301) were associated with HIV/HBV co-infection. Conclusions: The relative high prevalence of HIV/HBV co-infection and chronic nature call for the need of integrating HBV screening programs into HIV routine care to reduce morbidity and mortality levels caused by HIV/HBV co-infection.


Introduction
Chronic hepatitis B virus (HBV) infection is present in 2.7 million of the 36.7 million people infected with the human immunodeficiency virus (HIV) worldwide [1]. The overall prevalence of HIV/HBV co-infection is estimated at 7.4% with 1.96 million co-infected persons (71%) living in Sub-Saharan Africa [1].
This prevalence varies with rates estimated to be between 5% and 10% in regions such as North America, Europe and Australia compared to higher rates, between 20% and 30%, in Sub-Saharan Africa and Asia where more than 70% of the 36.7 million people infected with HIV live [1] [2]. HIV/HBV co-infection is common because of the shared transmission routes for these two viruses, including the parenteral route, the mother-child route and the sexual route. This co-infection has become one of the morbidity and mortality factors including the rapid progression of hepatic lesions to cirrhosis and for hepatocellular carcinoma associated with HBV infection compared to mono-infected HIV or HBV patients [3]. Although the specific mechanisms through which HBV interacts with HIV to influence the progression of the disease are not clearly understood up today, HIV/HBV co-infection has been identified as being responsible for higher levels of HBV replication and decreased spontaneous clearance of HBV with a higher risk of reactivation of HBV infection and death from liver complications due to hepatic failure, cirrhosis and hepatocellular carcinoma [3] [4] [5].
In sub-Saharan Africa, it is estimated that approximately 10% -20% of HIV-infected patients are HBsAg positive [6]

Statistical Analysis
HBV prevalence estimates were calculated with 95% confidence intervals (CI).
Sociodemographic characteristics, clinical and laboratory data were recorded in a standardized form and data were entered into an electronic database in Excel (version 10). Descriptive analyses were performed using means and proportion as well as standard deviations and 95% confidence interval where necessary. As-

Regulatory Approval
Ethics approval was obtained from the Ethics Committee of the Catholic University of Bukavu (Reference No. UCB/CIE/NC/001/7/2017).

Results
In our study, 198 HIV-infected patients were enrolled. The median age of the study participants was 43 years old (IQR 41 -45) and 12.90% (8/62) were men.  Viral encephalitis was strongly associated with co-infection (p < 0.0001), while, all other opportunistic infections observed in this study did not differ between those with and without co-infection (Table 2).

Discussion
We found in HIV-infected patients, HBV prevalence of 7.07% in our study setting, which is in agreement with HIV/HBV co-infection prevalence reported  [17]. However, other studies did document higher prevalence rates beyond 8% [16] [18]- [29]. Indeed, in a meta-analysis by Barth et al., data on the prevalence of HIV-HBV co-infection in some sub-Saharan African countries show very high rates with an average prevalence of 15% [30]. Other studies had reported lower prevalences of HIV/HBV co-infection than reported in this study [29] [31] [32]. progress to cirrhosis and hepatocellular carcinoma [3].
In this cohort, the HBV contact marker (HBc antibody) was prevalent in 33.33% and 3.03% of the participants had isolated anti HBcAb. This result was higher than what was reported by others authors [33] [34] [35]. However, this prevalence was lower than that described in Rwanda by Rusine et al. [29]. The prevalence of isolated HBc antibody in HIV-infected patients ranges from 17% to 81% and depends on the prevalence of HBV infection [34] [35] [36] [37]. We specify that 3.03% of the participants had isolated anti HBcAb. It is likely that this would be related to either to the loss of the post-contact immunization marker or the presence of the occult HBV described as the appearance of replication, HBV DNA in the liver with surface antigen of hepatitis B negative as shown by some authors [25]. A major limitation in this study is that we could not investigate occult HBV infections in participants who were HBsAg-negative but anti HBc-positive by HBV DNA PCR testing. Occult active HBV infections are thought to be common among HIV patients, with reported prevalence rates ranging from 10% -14% [38] [39] [40] and up to 89% in one study in South Africa [41]. Further research is needed to determine the prevalence of occult HBV in this group.  [26] and in Zambia by Wandeler et al. [16] but higher than the 15% prevalence that was described in a study conducted in Uganda [17]. It was lower than the 62% reported in a second Ghana study [42]. The prevalence of chronic non-replicative infection of 57.19% in co-infected patients found in this study, the latter is higher than that of 47.9% reported in Ghana [26] and in 33.3% reported in Zambia [16].
We observed that 36.87% of subjects were HBV immunization marker carries (defined as HBsAb positive) and in those, 68.49% had obtained immunization after HBV infection (HBcAb positive). This prevalence was similar to that reported by Boyd et al. [43]. However, it was slightly higher than the 14% to 50% prevalence in other cohorts of co-infected treated patients [10] [14] [24] [44] but similar to that between 50% and 71% in patients infected with HBV alone [31] [45] [46]. Also, these prevalences data are higher than those reported from Maputo, where less than 1% of co-infected subjects carried the marker for HBV immunization [23]. This loss of immunity against hepatitis B was explained by the fact that HIV infection leads to immunosuppression which would reduce the reaction.
Male sex was associated to co-infection significantly with co-infection as has been reported in Benin [28], Nigeria [31], South Africa [27], Rwanda [29] and Cameroon [19]. Other authors have reported a female predominance in Mozambique and Zambia [16] [23], Uganda [17], and in South Kivu [12]. In observing our study population, there were a large number of female than male patients. But by observing HIV/HBV co-infection, female subjects were less infected than male subjects. The higher proportion of women in our setting may be due to the higher accessibility of primary health care to women compared to men or other undocumented factors in our study.
In this study, the average age of co-infected patients was 44 ± 12 years. The 2008 South African study reported a similar average age of 41 years [27]. However, studies in Uganda, Kenya, Rwanda and Mozambique reported a much lower average age [14] [16] [17] [29]. These differences in average age could be due on the one hand to the introduction of the HBV vaccination program in some countries which would have significantly reduced the disease in younger age groups; and on the other hand to a recent introduction in the expanded immunization in children as is the case of our country or the absence of that program.
We also found that the majority (52.53%) of the patients in our study were in the WHO clinical I/II stage, but WHO clinical stage III/IV patients were more likely to be HIV/HBV co-infected (10.64%). Similarly, we observed that the degree of immunosuppression was more severe in co-infected subjects (50.00%) than in non-co-infected subjects (17.93%). Contrasting results were reported by Chambal  (75%) of the subjects were in WHO clinical stage I and II [22], which could account for the differences of findings. Regarding the impact of HBV on the progression of HIV infection, our data showed that CD4+ T cell counts were very low in co-infected patients than in HIV-infected patients alone. Previous studies have failed to demonstrate that HBV may accelerate or aggravate the natural history of HIV infection [47]. However, due to the cross-sectional design of our study, our data are subject to reverse causation limitation preventing us to assess the impact of HBV on HIV disease progression. Well-designed prospective studies are needed to derive these conclusions.

Conclusion
We found that the prevalence of HIV/HBV co-infection was 7.07% and all patients had chronic HBV infection. This study reinforces the importance of integrating HBV screening programs into HIV routine care to reduce morbidity and mortality levels caused by HIV/HBV co-infection.