Characterization of nevirapine resistance mutations in women with subtype A vs. D HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012)

J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):126-30. doi: 10.1097/00126334-200402010-00004.

Abstract

Objective: To compare the number and type of nevirapine (NVP) resistance mutations detected in Ugandan women with subtype A vs. D HIV-1 infection after single-dose NVP prophylaxis.

Design: In the HIVNET 012 trial, a higher rate of NVP resistance (NVPR) was seen in women with subtype D than A after single-dose NVP. In this study, the number and type of NVPR mutations detected 6-8 weeks after NVP were compared in women with subtypes A vs. D.

Methods: Plasma samples were available for 282 (92%) of 306 women who received NVP in HIVNET 012. Samples were analyzed with the ViroSeq HIV-1 Genotyping System (Applied Biosystems, Foster City, CA). Subtyping was performed by phylogenetic analysis of pol region sequences.

Results: Results were obtained for 279 women, including 147 with subtype A, 98 with subtype D, 6 with subtype C, and 28 with recombinant HIV-1. NVPR mutations were detected in 70 (25%) of 279 women. NVPR was more common in women with subtype D vs. A (35.7 vs. 19%, P = 0.0035). Complex patterns of NVPR mutations were detected in both subtypes. Among women with NVPR, 43% of women with subtype A and 46% of women with subtype D had >/=2 NVPR mutations. The mean number and pattern of NVPR mutations detected in women with subtypes A and D were similar.

Conclusions: This study confirms a higher rate of NVPR in women with subtype D than A and further defines the pattern of NVPR mutations that emerge 6-8 weeks after single-dose NVP prophylaxis in these subtypes.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Amino Acid Substitution
  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • HIV-1 / classification*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Mutation, Missense
  • Nevirapine / therapeutic use*
  • Phylogeny
  • Regression Analysis
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Viral Load

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Nevirapine