Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Autor: Anna Gamell, Lukas Muri, Hansjakob Furrer, Ingrid Felger, Emilio Letang, Manuel Battegay, Marcel Tanner, Tracy R. Glass, Christoph Hatz, Lameck B. Luwanda, Alex J. Ntamatungiro, Thomas Klimkait
Rok vydání: 2017
Předmět:
Male
Rural Population
0301 basic medicine
Pediatrics
Cross-sectional study
HIV Infections
Drug resistance
Tanzania
0302 clinical medicine
Prevalence
Immunology and Allergy
Medicine
adolescents
Prospective Studies
Treatment Failure
030212 general & internal medicine
610 Medicine & health
Child
Prospective cohort study
Surveillance
Reverse-transcriptase inhibitor
viral failure
Clinical Science
Infectious Diseases
Anti-Retroviral Agents
Female
Viral load
HIV drug resistance
medicine.drug
medicine.medical_specialty
resource-limited settings
Adolescent
antiretroviral therapy
030106 microbiology
Immunology
Mutation
Missense

resistance
03 medical and health sciences
children
Drug Resistance
Viral

Humans
business.industry
HIV
Odds ratio
Confidence interval
Cross-Sectional Studies
Africa
570 Life sciences
biology
business
Zdroj: AIDS (London, England)
Muri, Lukas; Gamell, Anna; Ntamatungiro, Alex J; Glass, Tracy R; Luwanda, Lameck B; Battegay, Manuel; Furrer, Hansjakob; Hatz, Christoph; Tanner, Marcel; Felger, Ingrid; Klimkait, Thomas; Letang, Emilio (2016). Development of HIV drug resistance and therapeutic failure in children and adolescents in rural tanzania-an emerging public health concern. AIDS, 31(1), pp. 61-70. Lippincott Williams & Wilkins 10.1097/QAD.0000000000001273
ISSN: 0269-9370
DOI: 10.1097/qad.0000000000001273
Popis: 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.
Databáze: OpenAIRE