To The Editor:
The transmission routes of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) are similar. HBV and HCV coinfection is common in patients infected with HIV.1 The interaction of the viruses and the influence of coinfection on prognosis are not clear. To learn more about the influence of the interaction of the viruses on viral replication and the clinical outcome of the diseases, we conducted a study on patients with HIV/HBV/HCV triple infection.
The patients infected with HIV were former plasma donors and blood recipients in the 1990s, and some of the patients were injecting drug users. Patients whose CD4 T-lymphocyte count was <200 cells/μL received free antiretroviral therapy (ART). The antiretroviral drugs available in China were lamivudine (3TC), zidovudine (AZT), didanosine (ddI), stavudine (d4T), nevirapine (NVP) and efavirenz (EFV).
Blood samples were collected and plasma was separated for HBV marker, antibody to HCV, HBV DNA, HCV RNA, and antibody to HIV by enzyme-linked immunosorbent assay (ELISA) and Western blot tests after informed consent was obtained. The HBV DNA and HCV RNA were retested after every 6 months of treatment.
The hepatitis B surface antigen (HBsAg)-positive rate was 10.2% and the anti-HCV-positive rate was 85.9% among 510 patients infected with HIV through plasma donation. Among 282 blood recipients, the HBsAg-positive rate was 10.3% and the anti-HCV-positive rate was 57.8%. Among 189 injecting drug users, the HBsAg positive rate was 10.1% and the anti-HCV-positive rate was 74.1%. The HIV/HBV/HCV triple-infection rates among plasma donors, blood recipients, and injecting drug users were 6.9%, 6.0%, and 8.5%, respectively.
Fifty-five patients with HIV/HBV/HCV triple infection and 73 patients with HIV/HBV dual infection were studied. The average ages of these patient groups were 39.8 years and 37.5 years, respectively, and the male-to-female ratios were 1:0.7 and 1:1 in the 2 groups, respectively. The positive rates of hepatitis B e antigen (HBeAg) in HBsAg-positive patients were 18.2% and 19.2%. Two hundred and 22 person-visits were conducted. In HBeAg-negative subjects, 24.5% and 54.8% had detectable serum HBV DNA in the HIV/HBV/HCV and HIV/HBV groups without 3TC treatment (P < 0.05, Table 1). The HBV DNA-positive rate was lower in HIV/HBV/HCV group. When ART, including 3TC regimens, was initiated, only 5.6% of individuals had detectable serum HBV DNA in the HIV/HBV/HCV group, whereas 30% in the HIV/HBV group had detectable serum HBV DNA after 15 months of treatment (P < 0.05, Table 1). The efficacy of 3TC on HBV DNA was stronger in the HIV/HBV/HCV group. In the HIV/HBV/HCV triple-infection group, detectable HCV RNA was seen more commonly in patients treated with ART that included 3TC (80%) compared with patients who received ART without 3TC (42.9%) (P < 0.05, Table 1). The occurrence of end-stage liver diseases and mortality caused by liver diseases was lower in patients with triple infection versus patients with HIV/HBV dual infection (0.53 vs. 2.44 per 100 person-years and 0.40 vs. 1.22 per 100 person years, respectively; P < 0.05) after follow-up through 748 and 656 person-years.
HCV may have a suppression effect on HBV replication in patients with triple infection who were positive for HBV DNA but negative for HBeAg. This phenomenon was not seen in HBeAg-positive patients, however. The mechanism accounting for the suppression effect of HCV on HBV was investigated by Shih et al2 and Chen et al.3 Whether the suppression effect of HCV on wild and precore mutant HBV is different is requires more study.
In patients with HIV/HBV/HCV triple infection and HIV/HBV dual infection, the suppression effect on HBV replication by 3TC was seen, especially in patients with HIV/HBV/HCV triple infection. It seems that HCV may enhance the efficacy of 3TC.
In China, anti-HIV drugs are limited and the side effects caused by 3TC are mild; thus, ART regimens that include 3TC are a common choice for patients who have AIDS, especially for HIV/HBV-coinfected patients. In patients with HIV/HBV/HCV triple infection, the use of ART that includes 3TC suppresses the replication of HBV; at the same time, the replication of HCV is increased. Further study is needed on the best ART regimens for patients with HIV/HBV/HCV triple infection.
After ART was initiated, the length of survival of patients with AIDS was prolonged. Occurrence of end-stage liver diseases and mortality caused by liver diseases increased, however.4 HBV and HCV coinfection may influence the occurrence of end-stage liver diseases in HIV-infected patients, but the explanation for this is not clear. Study of more cases and longer periods of follow-up are needed.
Yang Rong-rong, MD
Gui Xi-en, MD
Gao Shi-cheng, MD
Zhang Yong-xi, MD
Department of Infectious Diseases Zhongnan Hospital of Wuhan University Wuhan, China
1. Soriano V, Barreiro P, Martin Carbonero L, et al. Treatment of chronic hepatitis B or C in HIV-infected patients with dual viral hepatitis. J Infect Dis
2. Shih CM, Lo SJ, Miyamura T, et al. Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol
3. Chen SY, Kao CF, Chen CM, et al. Mechanism for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. J Biol Chem
4. Vallet-Pichard A, Pol S. Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. J Hepatol
. 2006;44(Suppl 1):S28-S34.