4.7 Article

Time trends in primary HIV-1 drug resistance among recently infected persons

Journal

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
Volume 288, Issue 2, Pages 181-188

Publisher

AMER MEDICAL ASSOC
DOI: 10.1001/jama.288.2.181

Keywords

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Funding

  1. NIAID NIH HHS [AI 41531] Funding Source: Medline
  2. NIMH NIH HHS [MH64384-01, P30 MH59037] Funding Source: Medline
  3. ODCDC CDC HHS [U64/CCU913941] Funding Source: Medline

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Context Transmission of multiclass drug-resistant human immunodeficiency virus type 1 (HIV-1) may increase with wider use of antiretroviral therapy. Objective To determine trends in prevalence of HIV-1 drug resistance among recently infected individuals in a geographic area with a high penetration of antiviral treatment. Design, Setting, and Patients Consecutive case series of 225 patients referred to a San Francisco, Calif, hospital with recent HIV-1 infection from June 1996 through June 2001. Main Outcome Measure Time trends in the prevalence of genotypic and phenotypic primary drug resistance. Results Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) steadily increased from 0% in 1996-1997 to 12 (13.2%) in 20002001 (P=.01). There was 1 mutation associated with protease inhibitor resistance in 19961997 (2.5%) and there were 7 (7.7%) in 2000-2001 (P=.25). Genotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) initially decreased and then returned to prior levels (P=.007 for test of homogeneity). Genotypic resistance to 2 or more classes of drugs increased from 1 (2.5%) to 12 (13.2%) (P=.004), but only 1 infection (1.2%) in the latter period was resistant to all 3 classes of agents (P=.58). Primary phenotypic resistance decreased for NRTIs from 21% to 6.2% (P=.03) and increased for NNRTIs from 0 to 8 (9.9%) (P=.02). Phenotypic resistance increased for protease inhibitors from 2.6% to 6.2% (P=32). Median time to virologic suppression (<500 copies/mL) during therapy was 12 weeks for patients with genotypic evidence of resistance compared with 5 weeks for patients with drug-sensitive infections (P=.02). Conclusions The frequency of primary resistance to NNRTIs is increasing, although resistance to all available classes of antiretroviral therapy remains rare. Genotypic resistance testing in recently infected persons predicts time to viral suppression during therapy.

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