Document Detail


Long-term virologic response and genotypic resistance mutations in HIV-1 infected Kenyan children on combination antiretroviral therapy.
MedLine Citation:
PMID:  23196827     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first line and second line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts.
METHODS: Children aged 18 months to 12 years initiated first-line cART and were followed every 1-3 months, for up to 5.5 years. Treatment was switched to second-line cART based on clinical and immunologic criteria according to national guidelines. Virologic failure was determined retrospectively as defined by ≥2 viral loads >5000 copies per milliliter. Drug resistance was assessed during viral failure by population-based sequencing.
RESULTS: Among 100 children on first-line cART followed for a median of 49 months, 34% children experienced virologic failure. Twenty-three (68%) of the 34 children with viral failure had detectable resistance mutations, of whom 14 (61%) had multiclass resistance. Fourteen (14%) children were switched to second-line regimens and followed for a median of 28 months. Retrospective analysis revealed that virologic failure had occurred at a median of 12 months before switching to second line. During prolonged first-line treatment in the presence of viral failure, additional resistance mutations accumulated; however, only 1 (7%) of 14 children had persistent viremia during second-line treatment.
DISCUSSION: Virologic suppression was maintained on first-line cART in two-thirds of HIV-infected children for up to 5 years. Switch to second line based on clinical/immunologic criteria occurred ∼1 year after viral failure, but the delay did not consistently compromise second-line treatment.
Authors:
Dalton C Wamalwa; Dara A Lehman; Sarah Benki-Nugent; Melanie A Gasper; Richard Gichohi; Elizabeth Maleche-Obimbo; Carey Farquhar; Grace C John-Stewart; Julie Overbaugh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  62     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-08-08     Completed Date:  2013-08-20     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  267-74     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Anti-Retroviral Agents / therapeutic use*
Child
Child, Preschool
Cohort Studies
DNA Mutational Analysis
Drug Resistance, Viral* / genetics
Drug Substitution
Drug Therapy, Combination
Female
Follow-Up Studies
HIV Infections / drug therapy*,  genetics,  virology
HIV-1 / genetics
Humans
Infant
Kenya
Male
Proportional Hazards Models
Treatment Failure
Viral Load
Grant Support
ID/Acronym/Agency:
AI076105/AI/NIAID NIH HHS; D43-TW000007/TW/FIC NIH HHS; K01 NS080637/NS/NINDS NIH HHS; K24 HD054314/HD/NICHD NIH HHS; K24-HD054314/HD/NICHD NIH HHS; P30 CA015704/CA/NCI NIH HHS; R01 AI076105/AI/NIAID NIH HHS; R01 HD023412/HD/NICHD NIH HHS; R01 TW007632/TW/FIC NIH HHS; R01-TW007632/TW/FIC NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Retroviral Agents
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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