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...
| Những tác giả chính: | , , , , , , , , , , , |
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| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
BioMed Central
2011
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| Những chủ đề: |
| _version_ | 1826289189572837376 |
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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. |
| first_indexed | 2024-03-07T02:25:07Z |
| format | Journal article |
| id | oxford-uuid:a554543c-bc37-41f5-a699-61d078dc570f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:25:07Z |
| publishDate | 2011 |
| publisher | BioMed Central |
| record_format | dspace |
| 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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