HIV-HBV Dual infection is not uncommon where both diseases are endemic. We assessed the level and impact of this co-infection among both AIDS and non-AIDS patients. Comparing these infections provided an insight into the role of co-infection in disease progression in chronic HBV carriers .
The HBsAg prevalence detected in HIV infected individuals was 12.2% with 78.1% positivity for either HBsAg or anti-HBc, which is comparable to the overall levels obtained in children [10, 11] and in controls from a liver cancer case control study . 62% of the children were infected with HBV with between 17-36% HBsAg positivity and highest rates of HBsAg carriage was reported in the younger children. The controls in the Kirk et al., study consisted of mainly adults with no liver related disease. Since The Gambia has low levels of HIV infection, with reported rates of 1-3% in the general population , the similarity of HBV prevalence reported in the previous studies and in the HIV- positive population in our study suggests that people infected with HIV do not have greater exposure or susceptibility to HBV than the general population.
Unlike the situation in the U.S. and Europe, HBV in sub Saharan Africa is commonly transmitted during childhood between siblings, typically long before infection with HIV , Burkina Faso  and Cote d'Ivoire Coast [25, 27–29]. Over 30% of co-infected HBsAg carriers >25 yrs old were positive for hepatitis B e antigen (HBeAg), this is greater than the rate reported in similar age group in a non-HIV population of which the adult HBV carriers were found to be in the inactive carrier phase . This is the third phase of chronic hepatitis B that is traditionally identified by the absence of HBeAg and HBV DNA for potentially indefinite duration. Thus similar to reports from other African studies, HBe antibody seroconversion occurred less frequently in Gambian HIV-infected individuals suggesting that HIV infection either delayed transition to the inactive carrier phase [31–34] or facilitate re-emergence of HBV replication. This has serious implications as studies have shown that patients who test positive for HBeAg and/or raised HBV DNA are those who are at highest risk of developing advanced liver disease [35, 36].
The degree of immunodeficiency represents an important factor in the progression of hepatitis among individuals co-infected with HBV and/or HCV . There is the risk of reactivation of chronic hepatitis B in HBV, sometimes referred to as reverse seroconversion , and occult hepatitis B. Occult hepatitis, defined by undetectable serum HBsAg combined with measurable serum HBV DNA, may be associated with progression to cirrhosis and HCC  in co-infected patients. It is anticipated that the natural history of HBV will change in sub-Saharan Africa as more countries introduce infant vaccination; this is likely to influence the rate of HBV-HIV co-infection in the future. In The Gambia HBV vaccination is done in infancy, the first dose given between the ages of 1 and 4 weeks, with a coverage rate of >80% . However universal vaccination was introduced only 19 years ago so subjects in the current study over 19 years old would not have had the opportunity to be vaccinated.
The HCV seroprevalence of 0.9% RIBA positive was lower than the frequency reported in other countries in Africa of 1.6-6.0% . Although HCV had been found to be of low prevalence in the Gambia, a surprisingly high frequency of 19.0% was once reported in HCC patients from a HCC case control study . In our study 7 out 572 HIV positive individuals were co-infected with HCV and this was observed exclusively in the older individuals and none of them were HBV carriers.
The age distribution of HCV infection was previously reported in a Gambian study of HIV negative individuals and a cohort effect was proposed as a possible reason for this finding . Our study confirmed the presence of genotype 2, similar to the findings in Guinea Conakry and Guinea Bissau [40, 41]. However like the Ruggieri et al., study, we showed heterogeneity in subtype clustering. Similar low rate of HCV-HBV co-infection was also reported in a previous study in Gambian patients referred for HIV screening . The high rate of false positive with the ELISA test could be due to amino acid sequence variability and purity of the HCV antigen used in the assays. The sensitivity and specificity of the HCV ELISA have been shown to be influenced by high immunoglobulin G (IgG) concentration of human blood . The lack of amplification with the 3 anti-HCV positive samples may be ascribed to a low viral RNA content or to virus degradation.
The over representation of HIV-1 in the AIDS group (over 5-fold higher than HIV-2) compared to the non-AIDS group is consistent with previous reports of a longer median time to AIDS in HIV-2 with a comparatively smaller proportion of HIV-2 infected patients developing AIDS
We observed a striking gender difference between the two HIV groups registering a female to male ratio of over 2.5. Since this was a clinic based study, in the absence of incidence data, it is unclear whether the gender distribution of HIV infection or HBV/HCV co-infection reflects the general population. However, these results are similar to a report from a national population-based HIV prevalence surveys conducted in 19 countries in sub-Saharan Africa, which showed a predominance of females in the HIV infected groups, with the lowest female: male ratio reported at 2.2[43, 44]. Despite the over representation of women in the two HIV positive groups, a higher proportion of HIV positive men had detectable HBV DNA compared to their female counterparts, suggesting a higher level of viral activity which could lead to higher rate of liver disease in males. This findings complements results from previous studies that showed higher proportion of men (male: female sex ratio around 2.4) with advanced liver diseases compared to women . Despite the difference in gender distribution of hepatocellular carcinoma especially in men in high-risk geographical areas, there is little documented evidence for sex-linked differences in HBV replication .
In conclusion, we showed that the prevalence of HBV chronic infection in HIV positive subjects in the Gambia was similar to that found in the general population. Co-infection with HIV however can lead to higher frequency of HBeAg positivity and higher levels of HBV DNA indicating higher levels of HBV replication.
Studies on the impact of HIV infection in the natural history of chronic HBV and the effect of chronic hepatitis B on immune recovery are necessary. The question as to whether there is a lower or delayed increase of CD4 lymphocyte count in HIV/HBV co-infected patients on ART is currently being investigated by our group. The current study recommends HBsAg screening for HIV patients before the start of ART.
This work was supported by Medical research Council (The Gambia) and with a small grant from Professor Richard Tedder.