Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D

Tamara S. Flys, Shu Chen, Dana C. Jones, Donald R. Hoover, Jessica D. Church, Susan A. Fiscus, Anthony Mwatha, Laura A. Guay, Francis Mmiro, Philippa Musoke, Newton Kumwenda, Taha E. Taha, J. Brooks Jackson, Susan H. Eshleman

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P < 0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

Original languageEnglish (US)
Pages (from-to)610-613
Number of pages4
JournalJournal of acquired immune deficiency syndromes
Volume42
Issue number5
DOIs
StatePublished - Aug 2006

Keywords

  • Africa
  • HIV-1
  • Mother-to-child transmission
  • Nevirapine
  • Resistance

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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