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Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.


ABSTRACT: Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. We retrospectively reviewed genotype data from paired samples in a cohort of HIV-1-infected Nigerian patients failing first-line antiretroviral therapies containing zidovudine (AZT) or tenofovir (TDF). Samples for each patient were taken at initial confirmed virological failure ?1000 copies/ml (S1) and then at the latest available sample with viral load ?1000 copies/ml before switch to second line (S2). Among 103 patients failing AZT, 19 (18.4%) had TAM-1s, 29 (28.2%) TAM-2s, and 21 (20.4%) mixed TAMs by S2. In contrast, in the 87 patients failing TDF, drug resistance mutations at S2 included K65R in 56 (64.4%), TAM-1s in 1 (1.1%), and TAM-2s in 25 patients (28.7%). Interestingly, 30.4% of patients with K65R in our study developed TAMs. These were exclusively K219E?±?D67N and were not predicted to confer a resistance cost to future AZT-containing regimens.

SUBMITTER: Chaplin B 

PROVIDER: S-EPMC6836671 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.

Chaplin Beth B   Imade Godwin G   Onwuamah Chika C   Odaibo Georgina G   Audu Rosemary R   Okpokwu Jonathan J   Olaleye David D   Meloni Seema S   Rawizza Holly H   Muazu Mohammad M   Musa Adesola Z AZ   Samuel Jay J   Agbaji Oche O   Ezechi Oliver O   Idigbe Emmanuel E   Kanki Phyllis J PJ  

AIDS research and human retroviruses 20171130 2


Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. We retrospectively reviewed genotype data from paired samples in a cohort of HIV-1-infected Nigerian patients failing first-line antiretroviral therapies containing zidovudine (AZT) or tenofovir (TDF). Samples for each patient were taken at initial confirmed virological failure ≥1000 copies/ml (S1) and then at the latest available sample with viral load ≥1000 copies/ml b  ...[more]

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