Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy

Clin Infect Dis. 2009 Feb 15;48(4):462-72. doi: 10.1086/596486.

Abstract

Objective: We investigated whether there are long-lasting effects of exposure to single-dose nevirapine (sdNVP) treatment on virologic response to nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy among human immunodeficiency virus (HIV)-infected women.

Methods: An observational epidemiologic study was conducted in Johannesburg, South Africa. Initial and sustained virologic response to NNRTI-based therapy was compared between 94 HIV-infected women who had received sdNVP 18-36 months earlier and 60 unexposed, HIV-infected women who had been pregnant 12-36 months earlier. Viral load was measured every 4 weeks up to week 24 and then every 12 weeks up to week 78. Time to viral suppression (viral load, <50 copies/mL) and confirmed rebound in the viral load (viral load, >400 copies/mL) were compared. Drug resistance was assessed using K103N allele-specific real-time polymerase chain reaction assay and population sequencing.

Results: Almost all women (97.5% of sdNVP-exposed women and 91.3% of sdNVP-unexposed women; P = .21) achieved viral suppression by week 24, and similar percentages of sdNVP-exposed and -unexposed women (19.4% and 15.1%, respectively) experienced viral rebound within 78 weeks after treatment (P = .57). K103N was detected with the K103N allele-specific real-time polymerase chain reaction assay among sdNVP-exposed and -unexposed women before treatment; detection was strongly predictive of inadequate viral response: 60.9% of women for whom K103N was detected in either viral RNA or DNA did not experience viral suppression or experienced viral rebound, compared with 15.1% of women for whom K103N was not detected (P < .001). After treatment, the M184V mutation occurred less frequently among sdNVP-exposed women than among sdNVP-unexposed women, but the frequency of NNRTI-associated mutations was similar between these groups of women with inadequate virologic response.

Conclusions: Exposure to sdNVP in the prior 18-36 months was not associated with a reduced likelihood of achieving and sustaining viral suppression while receiving NNRTI-based therapy. However, women with minority K103N mutations before treatment had a reduced durability of virologic suppression.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Longitudinal Studies
  • Molecular Sequence Data
  • Mutation, Missense*
  • Nevirapine / therapeutic use*
  • Sequence Analysis, DNA
  • South Africa
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Nevirapine
  • HIV Reverse Transcriptase

Associated data

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