Drug resistance and coreceptor usage in HIV type 1 subtype C-infected children initiating or failing highly active antiretroviral therapy in South Africa.
AIDS Res Hum Retroviruses
; 28(4): 324-32, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-21819257
ABSTRACT
HIV-1 drug resistance monitoring in resource-poor settings is crucial due to limited drug alternatives. Recent reports of the increased prevalence of CXCR4 usage in subtype C infections may have implications for CCR5 antagonists in therapy. We investigated the prevalence of drug resistance mutations and CXCR4 coreceptor utilization of viruses from HIV-1 subtype C-infected children. Fifty-one children with virological failure during highly active antiretroviral therapy (HAART) and 43 HAART-naive children were recruited. Drug resistance genotyping and coreceptor utilization assessment by phenotypic and genotypic methods were performed. At least one significant drug resistance mutation was present in 85.4% of HAART-failing children. Thymidine analogue mutations (TAMs) were detected in 58.5% of HAART-failing children and 39.0% had ≥3 TAMs. CXCR4 (X4) or dual (R5X4)/mixed (R5, X4) (D/M)-tropic viruses were found in 54.3% of HAART-failing and 9.4% of HAART-naive children (p<0.0001); however, the HAART-failing children were significantly older (p<0.0001). In multivariate logistic regression, significant predictors of CXCR4 usage included antiretroviral treatment, older age, and lower percent CD4(+) T cell counts. The majority of genotypic prediction tools had low sensitivity (≤65.0%) and high specificity (≥87.5%) for predicting CXCR4 usage. Extensive drug resistance, including the high percentage of TAMs found, may compromise future drug choices for children, highlighting the need for improved treatment monitoring and adherence counseling. Additionally, the increased prevalence of X4/D/M viruses in HAART-failing children suggests limited use of CCR5 antagonists in salvage therapy. Enhanced genotypic prediction tools are needed as current tools are not sensitive enough for predicting CXCR4 usage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triazóis
/
Receptores de HIV
/
HIV-1
/
Soropositividade para HIV
/
Fármacos Anti-HIV
/
Cicloexanos
/
Terapia Antirretroviral de Alta Atividade
/
Farmacorresistência Viral
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
/
Humans
/
Male
País/Região como assunto:
Africa
Idioma:
En
Revista:
AIDS Res Hum Retroviruses
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
África do Sul