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Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including Lamivudine for Patients Coinfected with HIV and HBV in China.

Gu L, Han Y, Li Y, Zhu T, Song X, Huang Y, Yang F, Guan S, Xie J, Gohda J, Hosoya N, Kawana-Tachikawa A, Liu W, Gao GF, Iwamoto A, Li T, Ishida T - PLoS ONE (2015)

Bottom Line: HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups.By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group.Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level.

View Article: PubMed Central - PubMed

Affiliation: China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China; Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

ABSTRACT
In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15-20% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV.

No MeSH data available.


Related in: MedlinePlus

Flowchart depicting the selection of patients for this study.
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pone.0134539.g001: Flowchart depicting the selection of patients for this study.

Mentions: This study was approved by the ethics committee at Peking Union Medical College Hospital (ClinicalTrials.gov Identifiers: NCT00618176 and NCT00872417). Patients were enrolled in Chinese cohort studies (National Key Technologies R&D Program for the 10th and 11th Five-year Plans) [16, 17] for examination of the response to the Chinese standard treatment regimen and the effectiveness of the treatment for HIV-1-infected patient. In these studies, patient selection and treatment methods were completely randomized. Informed consent was obtained from every participant. In China, patient plasma is collected at 12 centers (collaborative hospitals and local CDCs) that cover 23 provinces and cities (Beijing, Henan, Shaanxi, Shanghai, Fujian, Guangdong, Yunnan, Tianjin, Hebei, Neimenggu, Shandong, Liaoning, Jilin, Heilongjiang, Jiangsu, Zhejiang, Jiangxi, Shanxi, Anhui, Hunan, Hubei, Guangxi, and Sichuan). The patient plasma samples were collected between 2005 and 2014, and patients were classified according to the HBV-status criteria of the US Centers for Disease Control and Prevention [18]; these criteria have been used previously [16]. The flowchart in Fig 1 presents the patient-selection process, and Table 1 lists the clinical characteristics of the selected patients. We had access to stored patient blood samples collected before ART initiation (baseline) and after ART (12, 48, 96 weeks), and we selected 200 plasma samples from 50 patients who met previously described criteria [16]. Patients coinfected with hepatitis C virus were excluded from the analysis. The ART-3TC group comprised 38 patients who received treatment with 3TC/stavudine (d4T)/nevirapine (NVP) or 3TC/zidovudine (AZT)/NVP or 3TC/AZT/efavirenz (EFV) as first-line therapy, and the ART-3TC/TDF group included 12 patients who received 3TC/TDF/ritonavir-boosted lopinavir (LPV/r) or 3TC/TDF/EFV as first-line therapy (Table 1).


Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including Lamivudine for Patients Coinfected with HIV and HBV in China.

Gu L, Han Y, Li Y, Zhu T, Song X, Huang Y, Yang F, Guan S, Xie J, Gohda J, Hosoya N, Kawana-Tachikawa A, Liu W, Gao GF, Iwamoto A, Li T, Ishida T - PLoS ONE (2015)

Flowchart depicting the selection of patients for this study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543549&req=5

pone.0134539.g001: Flowchart depicting the selection of patients for this study.
Mentions: This study was approved by the ethics committee at Peking Union Medical College Hospital (ClinicalTrials.gov Identifiers: NCT00618176 and NCT00872417). Patients were enrolled in Chinese cohort studies (National Key Technologies R&D Program for the 10th and 11th Five-year Plans) [16, 17] for examination of the response to the Chinese standard treatment regimen and the effectiveness of the treatment for HIV-1-infected patient. In these studies, patient selection and treatment methods were completely randomized. Informed consent was obtained from every participant. In China, patient plasma is collected at 12 centers (collaborative hospitals and local CDCs) that cover 23 provinces and cities (Beijing, Henan, Shaanxi, Shanghai, Fujian, Guangdong, Yunnan, Tianjin, Hebei, Neimenggu, Shandong, Liaoning, Jilin, Heilongjiang, Jiangsu, Zhejiang, Jiangxi, Shanxi, Anhui, Hunan, Hubei, Guangxi, and Sichuan). The patient plasma samples were collected between 2005 and 2014, and patients were classified according to the HBV-status criteria of the US Centers for Disease Control and Prevention [18]; these criteria have been used previously [16]. The flowchart in Fig 1 presents the patient-selection process, and Table 1 lists the clinical characteristics of the selected patients. We had access to stored patient blood samples collected before ART initiation (baseline) and after ART (12, 48, 96 weeks), and we selected 200 plasma samples from 50 patients who met previously described criteria [16]. Patients coinfected with hepatitis C virus were excluded from the analysis. The ART-3TC group comprised 38 patients who received treatment with 3TC/stavudine (d4T)/nevirapine (NVP) or 3TC/zidovudine (AZT)/NVP or 3TC/AZT/efavirenz (EFV) as first-line therapy, and the ART-3TC/TDF group included 12 patients who received 3TC/TDF/ritonavir-boosted lopinavir (LPV/r) or 3TC/TDF/EFV as first-line therapy (Table 1).

Bottom Line: HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups.By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group.Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level.

View Article: PubMed Central - PubMed

Affiliation: China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China; Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

ABSTRACT
In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15-20% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV.

No MeSH data available.


Related in: MedlinePlus