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

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...

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Main Authors: Stewart, B, Jobarteh, M, Sarge-Njie, R, Alabi, A, de Silva, T, Peterson, K, Peterson, I, Whittle, H, Rowland-Jones, S, Jaye, A, Cotten, M, Mendy, M
פורמט: Journal article
שפה:English
יצא לאור: BioMed Central 2011
נושאים:
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author Stewart, B
Jobarteh, M
Sarge-Njie, R
Alabi, A
de Silva, T
Peterson, K
Peterson, I
Whittle, H
Rowland-Jones, S
Jaye, A
Cotten, M
Mendy, M
author_facet Stewart, B
Jobarteh, M
Sarge-Njie, R
Alabi, A
de Silva, T
Peterson, K
Peterson, I
Whittle, H
Rowland-Jones, S
Jaye, A
Cotten, M
Mendy, M
author_sort Stewart, B
collection OXFORD
description 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.
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spelling oxford-uuid:a554543c-bc37-41f5-a699-61d078dc570f2022-03-27T02:39:44ZEmergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a554543c-bc37-41f5-a699-61d078dc570fVirusesPharmacologyInfectious diseasesAfricaEnglishSymplectic Elements at OxfordBioMed Central2011Stewart, BJobarteh, MSarge-Njie, RAlabi, Ade Silva, TPeterson, KPeterson, IWhittle, HRowland-Jones, SJaye, ACotten, MMendy, MBACKGROUND: 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.
spellingShingle Viruses
Pharmacology
Infectious diseases
Africa
Stewart, B
Jobarteh, M
Sarge-Njie, R
Alabi, A
de Silva, T
Peterson, K
Peterson, I
Whittle, H
Rowland-Jones, S
Jaye, A
Cotten, M
Mendy, M
Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.
title Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.
title_full Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.
title_fullStr Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.
title_full_unstemmed Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.
title_short Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa.
title_sort emergence of hbv resistance to lamivudine 3tc in hiv hbv co infected patients in the gambia west africa
topic Viruses
Pharmacology
Infectious diseases
Africa
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