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

Research output: Contribution to journalArticlepeer-review

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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