Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine

AIDS. 2007 Oct 1;21(15):2077-82. doi: 10.1097/QAD.0b013e3282703847.

Abstract

Objectives: Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. Repeat use of SD NVP for pMTCT may influence emergence and persistence of NVP-resistant variants.

Design: K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study.

Methods: Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N).

Results: Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. Detection of K103N was independently associated with detection of K103N 6-8 weeks after the first SD NVP exposure and with pre-NVP viral load. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure.

Conclusions: K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Drug Resistance, Viral / genetics
  • Female
  • Follow-Up Studies
  • HIV Infections / genetics*
  • HIV Infections / prevention & control
  • HIV Infections / transmission
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Nevirapine / administration & dosage
  • Nevirapine / pharmacology*
  • Pregnancy
  • Pregnancy Complications, Infectious / genetics*
  • Pregnancy Complications, Infectious / prevention & control
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Uganda
  • Viral Load

Substances

  • Reverse Transcriptase Inhibitors
  • Nevirapine