By the end of 2021, there were about 1.142 million HIV-1 infected patients with 111,000 newly infections in China . HIV and HBV have similar route of transmission in clinic and approximately 10% of HIV infected patients in China are chronically coinfected with HBV . HIV/HBV co-infection can accelerate the immune damage process of HIV/AIDS, aggravate the degree of liver inflammation damage and destruction of CD4 + T lymphocyte, promote liver inflammation necrosis and fibrosis, increase the risk of liver toxicity of drugs and resulting in significantly higher incidence of severe clinical outcomes and liver-related mortality than patients infected with either virus alone [3–5]. ACLF is defined as acute liver injury characterized by jaundice, coagulation dysfunction (serum TBil ≥ 85 µmol/L, PTA ≤ 40% or INR ≥ 1.5), ascites and/or hepatic encephalopathy within 1 month in patients with chronic liver disease or cirrhosis. According to the basis of different chronic liver diseases, ACLF was divided into three types: Type A is based on chronic non-cirrhotic liver disease, Type B is based on compensated cirrhosis and Type C is based on decompensated cirrhosis [6, 7]. There are many incentives for ACLF while the HBV infection is the main incentive in China, and ACLF is often seen in HIV/HBV co-infected patients.
Numerous previous studies have shown that the disease status, progression and regression of ACLF patients are closely correlated with the patients' autoimmune level and mechanism of injury [8–10]. The levels of inflammatory factors such as leukocytes, plasma CRP, TNF-α, IL-6 and IL-8 were significantly higher in patients with ACLF than in those without ACLF, while the levels of leukocytes and plasma CRP correlated with the severity of the disease in patients with ACLF. Pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) and cytokines can activate macrophages in the liver microenvironment and initiate natural immunity during inflammatory activity in ACLF patients, which causing immune damage to the liver . The composition ratio of peripheral blood Th17 cells was significantly higher in patients with HBV-ACLF than in patients with chronic HBV and healthy controls, which was positively correlated with serum ALT levels and liver tissue inflammatory activity . Meanwhile, the proportion of HBV-specific cytotoxic T lymphocytes and activated CD8 + T lymphocytes in peripheral blood and liver tissue is significantly increased in ACLF patients . A clinical study in China showed that patients with HIV/HBV-ACLF had lower ALT, ALB, Hb and PLT than patients with HBV-ACLF alone, but higher HBV DNA levels, which may be due to HIV co-infection resulting in impaired immune function, poorer disease status, lower degree of liver inflammatory response and weaker ability to clear HBV. In conclusion, the production of ACLF has an important correlation with the natural and acquired immunity, while patients with HIV/HBV-ACLF will face more complex clinical problems and severe clinical regression due to the continuous influence of both viruses in the body and the disruption of immune function.
There are recommended antiviral therapy for HIV/HBV co-infection in both domestic and international guidelines currently, but there are no clear recommendations for patients with ACLF. At present, it is believed that HIV/HBV co-infected people regardless of CD4 + T lymphocyte counts, as long as there is no indication for anti-HIV delayed treatment, it is recommended to start HAART programs which simultaneously against the HIV and HBV. Two kinds of nucleoside drugs with anti-HBV activity must be included to avoid the use of single drug which may induce HIV resistance. TAF/TDF plus 3TC/FTC can be considered as the backbone part of the HAART regimen, while the third kind of drugs include non-nucleoside reverse transcriptase inhibitors (NNRTIs such as EFV, RPV), protease inhibitors (PIs such as LPV/c, DRV/c) or integrase strand transfer inhibitors (INSTIs such as DTG, RAL). ETV cannot be considered part of the HAART regimen because of its weak anti-HIV activity [15, 16]. However, because most NNRTIs and PIs are hepatotoxic and can aggravate liver damage, they are contraindicated for use in ACLF. Previous clinical studies have shown that INSTIs can be used in patients with Child-Pugh A and B. However, there are no published safety data on the use of INSTIs in ACLF patients with severely impaired liver function . The usage of RAL + TDF + FTC as the regimen of HBV/HIV-acute liver failure patient has also been reported in the literature, but the patient eventually died due to overwhelming disease .
Both HIV/HBV co-infected patients in our case report met the diagnostic criteria for ACLF. Both patients had clear manifestations of chronic HBV infection with severe hepatic impairment and ascites prior to initiation of ART. Anti-infection therapy, plasma infusion, jaundice-relieving, diuretic, liver-protective and symptomatic treatments were immediately used to improve their clinical symptoms after admission. Considering the patient with Child-Pugh C, we used the HAART regimen of DTG + TDF + 3TC and closely monitored their liver function and coagulation function. Both patients showed gradual improvement in liver function and coagulation function after treatment. Post-discharge follow-up also showed no further deterioration of liver function in either patient, suggesting that the HAART regimen including DTG may be effective for HBV/HIV co-infected patients with cirrhotic decompensation or ACLF, which may help avoid liver transplantation. However, severe liver damage has also been reported in HBV/HIV co-infected patients with Child-Pugh A using HAART regimens containing DTG, which may be related to IRIS-induced liver inflammatory damage [19, 20]. Therefore, the use of HAART regimens containing INSTIs such as DTG in patients with ACLF still requires close monitoring of liver function.
In conclusion, for these two patients with HIV/HBV-ACLF, the attempted HAART treatment consist of DTG + TDF + 3TC was effective and did not result in serious liver damage, IRIS or other complications, which demonstrating the safety of DTG in patients with ACLF and Child-Pugh C. However, the clinical use of INSTIs is still in the exploratory stage because there are no relevant studies on the level of pharmacokinetics and safety of INSTIs in such patients. Although there are only two cases, our report suggests that patients with HIV/HBV-ACLF can be treated experimentally with INSTIs and provides some clinical basis for future relevant prospective studies.