In our study, 841 HIV/HBV co-infected patients (the prevalence rate was 4.3% among HIV-infected patients receiving ART) received ART for an average of 34.5 months, about 93.2% of them took drugs on time and the LTFU rate was 1.2%. The mortality rate of HIV/HBV co-infected patients was 0.5%, which was significantly lower than that of other studies (19.0%) [4,21,28]. We observed that HIV diagnosis to ART initiation interval, the initial incidence of OIs (9.3%) and baseline clinical characteristics ALT, AST for HIV/HBV co-infected patients were higher than those of HIV mono-infected patients. Moreover, baseline CD4 count, CD4/CD8 ratio, platelet and hemoglobin were lower in these patients. And, HBV coinfection affects the incidence of APRI≥0.5, but does not affect the incidence of CD4<200 cells/μL, CD4/CD8 ratio<0.30 and VL>400 copies/mL in HIV patients after the ART (Table 2).
After adjusting the effect of baseline CD4 count on indicator changes during ART, we found that CD4 count was still lower in HIV/HBV co-infected patients after ART treatment, but this difference was mainly affected by baseline CD4 count (Figure 1A) and the prevalence of CD4<200 cells/μL was also not higher than that in HIV mono-infected patients (Table 2), which further illustrated HBV co-infection does not affect the therapeutic effect of CD4 in HIV patients [1,4]. Further investigation demonstrated initial low CD4 count, duration of ART, initial OIs and WHO stage increased the prevalence of CD4<200 cells/μL in HIV patients. Besides, initial CD4 count affects the incidence of VL>400 copies/mL and LTFU or death (HR=0.784) in HIV patients (Table 2,3). Therefore, in order to better improve the ART effect of HIV/HBV patients, we should pay attention to the impact of these baseline CD4 [44,45].
The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events and higher ratio may reflect a more " normal " immune phenotype conferring enhanced prognosis and predict posttreatment control [46-49]. In this study, although the baseline CD4/CD8 ratio in HIV/HBV patients was lower than that in HIV mono-infected patients, there was not significant difference between the two groups patients after ART treatment. Also we found initial low CD4 count, initial low CD4/CD8 ratio, shorter duration of ART and second-line ART increased the prevalence of CD4/CD8 ratio <0.30 in HIV/HBV patients. Evidence have shown that initial CD4 count can affect the ratio in HIV patients [46,49-51]. Besides, 12% of HIV/HBV patients still receive CD4/CD8 ratio <0.30 after 34.5 months of ART.
Many studies have indicated that HIV/HBV coinfection may play a direct role in HCC, cirrhosis or liver fibrogenesis [1,32,52,53], and no clear reduction in end-stage liver disease (ESLD) risk was observed over 15 years in HIV patients, even after ART treatment . We can see that baseline ALT, AST and the rate of APRI≥0.5 were higher in HIV/HBV co-infected patients (Table1). During ART treatment, the ALT of HIV/HBV patients increased significantly between 0 and 3 months. And 3 months later, ALT gradually decreased and there was no difference with HIV mono-infected patients (Figure 1B). Besides, the rate of APRI≥0.5 in HIV/HBV co-infected patients was also higher, which mainly affected by initial APRI and HBV co-infection .In our study we also found that initital APRI≥0.5 (HR=4.6471, 95% CI 1.331-16.227) predicted for LTFU or death in HIV patients. Some studies have shown that higher AST appear to be important mortality risk factors in HIV/HCV-coinfection , both AST ,ALT and APRI to predict liverrelated mortality, either alone or as components of indices of liver fibrosis [28,53,56-58]. Besides, several studies have shown a significant correlation between APRI scores and HIV viremia levels [28,59,60]. Therefore, the changes of AST,ALT and APRI in HIV/HBV patients after ART treatment need to be noticed, early detection of possible liver injury in patients and adjustment of ART regimens.
Currently, we can observe an increasing number of studies focused on the non-AIDS complications in HIV patients [61-62], analyzing changes in biochemical indicators (e.g., cholesterol) in patients undergoing ART treatment [64,65].We found that in the course of ART treatment, the TG and TC means in HIV/HBV co-infected patients were lower than that in HIV mono-infected patients (Figure 1F-G),but the ratio of TC>5.69 mmol/L was no difference between them. HIV patients with ART are at increasing cardiovascular disease (CVD) risk and stroke, thus, the possibility to classify patients for lipid lowering treatment may be a useful tool for clinical management[66-69].But other studies showed that HIV patients with high serum total cholesterol have lower HIV RNA load and better CD4 T cell [65,70]. Therefore, there is need for prospective cohort or case control studies to determine the relationship between total cholesterol and ART outcomes in HIV patients.
Death and LTFU are the additional concerns in HIV patients [1,2,56,71,72]. With 34.5-month ART treatment, the overall mortality and loss to follow-up rate of HIV(0.3% and 0.5%) or HIV/HBV (0.7% and 1.4%) patients were lower in this study. And other studies show that LTFU at 6 and 12months compared with 9.3% and 14.4%[73-75]. The main reason may be the higher ART adherence (93%) of the HIV patients in our study. In addition to the two factors (CD4 and APRI≥0.45) mentioned above, we also found that intital OIs (HR=4.910) and age (HR=1.336) predicted for LTFU or death in HIV patients. In other studies, the overall prevalence of OIs among HIV/AIDS patients on ART was 32.5-48%[76,77], OIs that emerge very early after ART also confer an increased risk of early mortality .Besides, the impact of age on HIV patients has always been a topic.An exaplanation for this trend may be that older patients have poorer immunological responses than their younger counterparts . Furthermore, successful ART has led to a growing number of older HIV-1-infected individuals who face both age-related and HIV-1-related inflammation, which may synergistically promote physical decline [80,81].We also found that HBV co-infection had no effect on HIV patients' loss of follow-up or death [4,32,56].
Limitations of this study were also considered. Indeed, due to individual differences, it is impossible to collect timely drug replacement information of patients, so we analyzed the ART treatment of HIV/HBV patients as a whole. Additionally, laboratory examination of HIV patients could not guarantee that they would be checked during each follow-up. Finally, there are few data on mortality in HIV/HBV patients in this study. Further long-term study are needed about the ART effect of HIV/HBV disease progression.
In this cohort analysis of HIV/HBV co-infected patients on ART outcomes, we found that clinical indicators such as CD4 count, VL, CD4/CD8 ratio, AST, the prevalence of OIs and APRI≥0.5 were improved significantly over time on ART treatment. However, the abnormal rate of AST and APRI was higher in HIV/HBV patients, and CD4, TC and TG were lower than those in HIV patients. HBV co-infection affect the prevalence of APRI≥0.5, but it does not affect the abnormal incidence of other clinical indicators in HIV patients. Besides, initial CD4, APRI≥0.5 initial OIs status and age had related to LTFU or death among HIV patients rather than co-infection of HBV. Further long-term studies to examine the incidence of liver injury and death outcomes in HIV/HBV patients under good ART treatment are needed in prospective studies and in larger cohorts.