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Scientific article
English

Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types

Published inArchives of internal medicine, vol. 167, no. 16, p. 1782-1790
Publication date2007
Abstract

BACKGROUND: Standard first-line combination antiretroviral treatment (cART) against human immunodeficiency virus 1 (HIV-1) contains either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Differences between these regimen types in the extent of the emergence of drug resistance on virological failure and the implications for further treatment options have rarely been assessed. METHODS: We investigated virological outcomes in patients from the Swiss HIV Cohort Study initiating cART between January 1, 1999, and December 31, 2005, with an unboosted PI, a PI/r, or an NNRTI and compared genotypic drug resistance patterns among these groups at treatment failure. RESULTS: A total of 489 patients started cART with a PI, 518 with a PI/r, and 805 with an NNRTI. A total of 177 virological failures were observed (108 [22%] PI failures, 24 [5%] PI/r failures, and 45 [6%] NNRTI failures). The failure rate was highest in the PI group (10.3 per 100 person-years; 95% confidence interval [CI], 8.5-12.4). No difference was seen between patients taking a PI/r (2.7; 95% CI, 1.8-4.0) and those taking an NNRTI (2.4; 95% CI, 1.8-3.3). Genotypic test results were available for 142 (80%) of the patients with a virological treatment failure. Resistance mutations were found in 84% (95% CI, 75%-92%) of patients taking a PI, 30% (95% CI, 12%-54%) of patients taking a PI/r, and 66% (95% CI, 49%-80%) of patients taking an NNRTI (P <.001). Multidrug resistance occurred almost exclusively as resistance against lamivudine-emtricitabine and the group-specific third drug and was observed in 17% (95% CI, 9%-26%) of patients taking a PI, 10% (95% CI, 0.1%-32%) of patients taking a PI/r, and 50% (95% CI, 33%-67%) of patients taking an NNRTI (P <.001). CONCLUSIONS: Regimens that contained a PI/r or an NNRTI exhibited similar potency as first-line regimens. However, the use of a PI/r led to less resistance in case of virological failure, preserving more drug options for the future.

Keywords
  • Adult
  • Antiretroviral Therapy, Highly Active
  • Confidence Intervals
  • Drug Resistance, Multiple, Viral
  • Female
  • Follow-Up Studies
  • HIV Infections/ drug therapy/epidemiology/virology
  • HIV Protease Inhibitors/ therapeutic use
  • HIV-1/ drug effects/genetics
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • RNA, Viral/analysis
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors/ therapeutic use
  • Ritonavir/ therapeutic use
  • Switzerland/epidemiology
  • Treatment Outcome
Citation (ISO format)
VON WYL, Viktor et al. Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types. In: Archives of internal medicine, 2007, vol. 167, n° 16, p. 1782–1790. doi: 10.1001/archinte.167.16.1782
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ISSN of the journal0003-9926
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