Tuberculosis resistance-conferring mutations with fitness cost among HIV-positive individuals in Uganda.
Int J Tuberc Lung Dis
; 21(5): 531-536, 2017 05 01.
Article
en En
| MEDLINE
| ID: mdl-28399968
ABSTRACT
BACKGROUND:
Multidrug-resistant tuberculosis (MDR-TB) is considered to be less transmissible due to the fitness cost associated with drug resistance-conferring mutations in essential genes.OBJECTIVE:
To test the hypothesis that TB drug resistance-conferring mutations with fitness cost are more frequent among human immunodeficiency virus (HIV) positive than among HIV-negative patients.DESIGN:
We analysed all strains from the two TB drug resistance surveys conducted in Uganda between 2008 and 2011. Strains phenotypically susceptible to rifampicin and/or isoniazid were assumed to be wild-type; in all other cases, we performed whole-genome sequencing. Mutations at the rpoB531 and katG315 codons were considered without fitness loss, whereas other rpoB codons and non-katG were considered with fitness loss.RESULTS:
Of the 897 TB patients, 286 (32.1%) were HIV-positive. Mutations with fitness loss in HIV-positive and HIV-negative patients were respectively as follows non-531 rpoB 1.03% (n = 3), 0.71% (n = 4) (OR 1.46, 95%CI 0.58-3.68); non-katG 0.40% (n = 1), 1.0% (n = 6) (OR 0.40, 95%CI 0.07-2.20); rpoB531 1.49% (n = 4), 0.69% (n = 4) (OR 2.29, 95%CI 0.83-5.77); katG315 3.86% (n = 11), 2.55% (n = 15) (OR 1.54, 95%CI 0.81-2.90). The odds of mutations with and without fitness cost were higher for patients with a history of previous anti-tuberculosis treatment.CONCLUSIONS:
Our data do not support the hypothesis that resistance-conferring mutations with fitness cost are likely to be often present in HIV-positive individuals.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
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Tuberculosis Resistente a Múltiples Medicamentos
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Mycobacterium tuberculosis
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Antituberculosos
Tipo de estudio:
Health_economic_evaluation
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
País como asunto:
Africa
Idioma:
En
Año:
2017
Tipo del documento:
Article