Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States

Deborah Persaud*, Paul Palumbo, Carrie Ziemniak, Jie Chen, Stuart C. Ray, Michael Hughes, Peter Havens, Murli Purswani, Aditya H. Gaur, Ellen Gould Chadwick

*Corresponding author for this work

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Background. The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. Methods. We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4+ T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. Results. Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4 + T cell latent reservoir in all 5 infants. Conclusions. The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.

Original languageEnglish (US)
Pages (from-to)1402-1410
Number of pages9
JournalJournal of Infectious Diseases
Volume195
Issue number10
DOIs
StatePublished - May 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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