Journal article
Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern.
- Muri L aSwiss Tropical and Public Health Institute (Swiss TPH) bUniversity of Basel, Basel, Switzerland cIfakara Health Institute, Ifakara, United Republic of Tanzania dDivision of infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel eDepartment of Infectious Diseases, Bern University Hospital, University of Bern, Bern fMolecular Virology, Department Biomedicine Petersplatz, University of Basel, Basel, Switzerland gISGlobal, Barcelona Centre for Health Research (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
- Gamell A
- Ntamatungiro AJ
- Glass TR
- Luwanda LB
- Battegay M
- Furrer H
- Hatz C
- Tanner M
- Felger I
- Klimkait T
- Letang E
- 2016-09-28
Published in:
- AIDS (London, England). - 2017
Adolescent
Anti-Retroviral Agents
Child
Cross-Sectional Studies
Drug Resistance, Viral
Female
HIV
HIV Infections
Humans
Male
Mutation, Missense
Prevalence
Prospective Studies
Rural Population
Tanzania
Treatment Failure
English
OBJECTIVE
To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania.
DESIGN
Prospective cohort study with cross-sectional analysis.
METHODS
All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM.
RESULTS
Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11-13.68], female sex (aOR = 2.57; 95% CI 1.03-6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51-35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4 T-cell percentage (aOR = 0.20; 0.10-0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73-0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure.
CONCLUSION
Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.
To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania.
DESIGN
Prospective cohort study with cross-sectional analysis.
METHODS
All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM.
RESULTS
Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11-13.68], female sex (aOR = 2.57; 95% CI 1.03-6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51-35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4 T-cell percentage (aOR = 0.20; 0.10-0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73-0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure.
CONCLUSION
Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1097/QAD.0000000000001273
- PMID 27677163
- Persistent URL
- https://folia.unifr.ch/global/documents/140503
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