High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

Abstract

Objectives: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China. Methods: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed. Results: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3–96.7) was significantly higher than that in group 1 (1.4%, 95% CI –1.4 to 4.2; χ² = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 10⁶ copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations. Conclusion: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.

Long‐term observation on hepatitis B surface antigen seroclearance in therapy experienced HIV/HBV co‐infected Chinese

“…As is known, the emergence of HBV drug‐resistant mutations in HIV/HBV co‐infected patients who are on ART including 3TC and/or TDF is common . At 24 months, a very low prevalence (1.9%) of 3TC resistance was found in this study, compared to Gu L's report which indicated 16.0% of the patients harboured 3TC‐resistant mutants after 96‐week treatment .…”

The management of treatment-experienced HIV patients (including virologic failure and switches)

“…The use of 3TC or FTC as sole HBV-active drug is NOT recommended, as HBV resistance to these will likely develop rapidly. 68 Examples of recommended ARV switch strategies Based on results of previously published trials, the following are examples of antiretroviral therapy changes that could achieve simplification, improve tolerability, address drug-drug or drugfood interactions or be optimal in special situations such as pregnancy are presented below.…”

“…The use of 3TC or FTC as sole HBV-active drug is NOT recommended, as HBV resistance to these will likely develop rapidly. 68…”

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

“…22,43 The heterogeneous distribution of HBV drug-resistance mutations could be explained by factors such as the use of different detection methods (line probe assay, Sanger DNA sequencing, or next generation sequencing), the number of samples analyzed, accessibility of antiviral in each region, the period during which the studies were conducted, and even the distribution of HBV genotypes. [35][36][37][38][39][40][41][42][43] Here, we showed that HBV resistance mutations were common in genotypes H and A2. As mentioned before, the prevalence of genotype H was expected as it is predominant in Mexico.…”

“…The finding is consistent with what has been reported in other HIV cohorts. [37][38][39] Worldwide, the HBV drug resistance rate differs among countries. The highest frequencies have been detected in Italy (72.1%), 40 and a rate of 42.8% has been reported in ethnic regions of China.…”