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

J Acquir Immune Defic Syndr. 2006 Aug 15;42(5):610-3. doi: 10.1097/01.qai.0000221686.67810.20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Drug Resistance, Viral / genetics
  • Female
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Malawi
  • Mutation, Missense
  • Nevirapine / pharmacology*
  • Nevirapine / therapeutic use
  • Point Mutation
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / virology*
  • Statistics as Topic
  • Uganda

Substances

  • Anti-HIV Agents
  • Nevirapine