Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa

Abstract

Background: Lamivudine (3TC) is a potent inhibitor of both Hepatitis B virus (HBV) and Human Immunodeficiency Virus (HIV) replication and is part of first-line highly active antiretroviral therapy (HAART) in the Gambia. Unfortunately, the effectiveness of 3TC against HBV is limited by the emergence of resistant strains.

Aim: The aim of this retrospective study was to characterise 3TC-resistant mutations in HBV from co-infected patients receiving HAART, by generating HBV polymerase sequence data and viral loads from HBV genotype E infected patients, both at initiation and during a course of 3TC therapy.

Method: Samples from 21 HBV chronic carriers co-infected with HIV-1 (n = 18), HIV-2 (n = 2) and HIV-dual (n = 1) receiving HAART for a period of 6-52 months were analysed for the emergence of 3TC-resistance mutations.

Findings: Sixteen out of 21 HBV/HIV co-infected patients responded well to HAART treatment maintaining suppression of HBV viraemia to low (≤ 104 copies/mL) (n = 5) or undetectable levels (< 260 copies/ml) (n = 11). Out of the 5 non-responders, 3 had developed 3TC-resistant HBV strains showing mutations in the YMDD motif at position 204 of the RT domain of the HBV polymerase. One patient showed the M204V+ L180M+ V173L+ triple mutation associated with a vaccine escape phenotype, which could be of public health concern in a country with a national HBV vaccination programme. All except one patient was infected with HBV genotype E.

Conclusions: Our findings confirm the risk of 3TC mutations in HAART patients following monotherapy. This is a novel study on 3TC resistance in HBV genotype E patients and encourage the use of tenofovir (in association with 3TC), which has not shown unequivocally documented HBV resistance to date, as part of first-line therapy in HIV/HBV co-infected patients in West Africa.HBV- hepatitis B infection; HIV- human immunodeficiency virus; HAART- antiretroviral therapy.

Figure 1

Amino acid sequence alignment generated from samples at baseline and at most recent time points covering amino acids 161 - 236 of the HBV reverse transcriptase domain. The HBV RT sequences are aligned with reference genotype E sequence (X75664) which is shown at the top, alignment with patient sequence is shown below with identities marked as (.) and sequence changes indicated by letter. Sequences from patients who developed YMDD mutations (patients 6, 12 and 13) during 3TC therapy are shown at the top half of the figure. The baseline and post treatment time points are represented by '01' and '02' respectively.