Drug resistance at low viraemia in HIV-1-infected patients with antiretroviral combination therapy

Soo Aleman, Karin Söderbärg, Ubaldo Visco-Comandini, Gisela Sitbon, Anders Sönnerborg

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To study the appearance of drug-induced mutations at low viraemia in treated HIV-1-infected patients. Design and methods: Fourteen patients, who received their first (n = 5), second (n = 7) or third (n = 2) line antiretroviral combination therapy, developed a persistent low-grade viraemia after an initial decrease of the viral load (VL) to less than 500 copies/ml. The amount of HIV-1 RNA (n = 71) and reverse transcriptase (RT)/protease sequences (n = 56) were determined in longitudinally obtained plasma samples during a mean period of 16.6 months. Results: In the vast majority (93%) of patients, new primary resistance mutations were found in the RT and/or protease genes at virological failure at a median VL of 500 and 200 copies/ml, respectively. Drug-experienced patients developed mutations at a lower VL than naive patients. In one previously protease inhibitor-naive patient, primary RT and protease mutations were detected, although the VL was less than 50 copies/ml. A serial accumulation of drug resistance mutations was seen despite the VL increase being mostly modest, reaching a median of 1450 copies/ml at the end of the study, and the CD4 T cell counts continued to increase. One patient still had a VL of 300 copies/ml after 28 months, despite the presence of the multidrug-resistance Q151M mutation. Conclusion: Low viraemia after virological treatment failure can select for virus with several new drug resistance mutations, despite a concomitant increase in CD4 T cell counts. This serial accumulation of mutations is likely to exhaust future drug options.

Original languageEnglish
Pages (from-to)1039-1044
Number of pages6
JournalAIDS (London, England)
Volume16
Issue number7
DOIs
Publication statusPublished - May 3 2002

Keywords

  • Drug resistance
  • Failure
  • HIV-1
  • Low viraemia
  • Mutations
  • Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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