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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children
Journal of Acquired Immune Deficiency Syndromes, Volume 56, No. 1, Year 2011
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Description
Background:: Without virologic testing, HIV-infected African children starting antiretroviral (ARV) therapy are at risk for undetected virologic failure and the development of ARV resistance. We sought to determine the prevalence of early virologic failure (EVF), to characterize the evolution of ARV-resistance mutations and to predict the impact on second-line therapy. Methods: The prevalence of EVF (HIV RNA >400 copies/mL on sequential visits after 6 months of therapy) was identified among 120 HIV-infected Ugandan children starting ARV therapy. ARV mutations were identified by population sequencing of HIV-1 pol in sequential archived specimens. Composite discrete genotypic susceptibility scores were determined for second-line ARV regimens. Results: EVF occurred in 16 children (13%) and persisted throughout a median (interquartile ratio) 938 (760-1066) days of follow-up. M184V and nonnucleoside reverse transcriptase inhibitor-associated mutations emerged within 6 months of EVF; thymidine-analog-mutations arose after 12 months. Worse discrete genotypic susceptibility scores correlated with increasing duration of failure (Spearman R = -0.47; P = 0.001). Only 1 child met World Health Organization CD4 criteria for ARV failure at the time of EVF or during the follow-up period. Conclusions: A significant portion of HIV-infected African children experience EVF that would be undetected using CD4/clinical monitoring and resulted in the accumulation of ARV mutations that could compromise second-line therapy options. © 2010 by Lippincott Williams & Wilkins.
Authors & Co-Authors
Ruel, Theodore D.
United States, San Francisco
Ucsf School of Medicine
United States, Chicago
Division of Infectious Diseases
Kamya, Moses Robert K.
Uganda, Kampala
Makerere University
United States, Chicago
Division of Infectious Diseases
Li, Pelin
United States, San Francisco
Ucsf School of Medicine
Pasutti, William
United States, San Francisco
Ucsf School of Medicine
Charlebois, Edwin D.
United States, San Francisco
Ucsf School of Medicine
United States, Chicago
Division of Infectious Diseases
Liegler, Teri J.
United States, San Francisco
Ucsf School of Medicine
United States, Chicago
Division of Infectious Diseases
Dorsey, Grant M.
United States, San Francisco
Ucsf School of Medicine
United States, Arlington
Division of Hiv/aids
Rosenthal, Philip Jon
United States, San Francisco
Ucsf School of Medicine
United States, Arlington
Division of Hiv/aids
Havlir, Diane V.
United States, San Francisco
Ucsf School of Medicine
United States, Arlington
Division of Hiv/aids
Wong, Joseph K.
United States, San Francisco
Ucsf School of Medicine
United States, Arlington
Division of Hiv/aids
Achan, Jane
Uganda, Kampala
Makerere University
Statistics
Citations: 40
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1097/QAI.0b013e3181fbcbf7
ISSN:
15254135
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study