Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing antiretroviral therapy

Braz J Infect Dis. 2004 Aug;8(4):281-9. doi: 10.1590/s1413-86702004000400003. Epub 2004 Nov 19.

Abstract

We analyzed the first 96 patients tested for HIV resistance to antiretroviral therapy in three Brazilian states. The HIV-1 reverse transcriptase (RT) and protease (PR) were sequenced by using the ABI ViroSeq system. The drugs previously used for each patient were recorded and correlated with the mutations found in the samples. Viral load (VL) and CD4 count were also recorded. Only one patient had the wild type sequence. The most prevalent mutations were: 184V (59%), 41L (47.9%), 63P (53%), 215Y (50%), 36I (46%), 10I (35%), 67N (42%), 77I (37%), 90M (36%) and 210W (33%). A positive correlation between the number of previously used ARVs and the number of mutations was observed (p<0.05). Associations between mutations and ARV drugs were identified at positions 69, 118, 184 and 215 with previous exposure to NRTI, mutations at positions 98, 100, 103, 181 and 190 with previous NNRTI use and at positions 10, 20, 30, 46, 53, 54, 71, 73, 82, 84, 88 and 90 with previous PI therapy (p<0.05). Previous exposure to ARV drugs was associated with previous genotypic resistance to specific drugs, leading to treatment failure in HIV patients. Genotypic resistance was clearly associated with virological and immunological failure.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / virology*
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Drug Resistance, Multiple, Viral / genetics*
  • Female
  • Genotype
  • HIV Protease / genetics*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation
  • Treatment Failure
  • Viral Load

Substances

  • Anti-HIV Agents
  • HIV Reverse Transcriptase
  • HIV Protease