Geographic and temporal trends of transmitted HIV-1 drug resistance among antiretroviral-naïve subjects screening for two clinical trials in North America and Western Europe

HIV Clin Trials. 2009 Mar-Apr;10(2):94-103. doi: 10.1310/hct1002-94.

Abstract

Purpose: To determine the prevalence of transmitted drug resistance (TDR) in antiretroviral (ARV)-naïve HIV-1-infected subjects who were screened for two clinical trials by geographic region and time.

Methods: Studies M03-613 and M05-730 screened ARV-naïve subjects in 2004 and 2005-2006, respectively. Screening drug resistance genotype assays were performed using population sequencing, and prevalence of drug resistance mutations (DRMs) was assessed at 39 amino acid positions in HIV-1 protease and reverse transcriptase (RT) and compared between geographic regions and calendar years.

Results: In 913 subjects, the prevalence of DRMs was higher in North America than in Western Europe, including any DRM (13.6% vs. 6.8%, p < .001), non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (7.3% vs. 3.2%, p = .006), protease inhibitor (PI) DRMs (3.6% vs. 0.8%, p = .004), and nucleoside reverse transcriptase inhibitor (NRTI) DRMs (6.1% vs. 3.8%, p = ns). The prevalence of TDR to NNRTIs was higher compared to PIs within each region (p = .031 for North America, and p = .011 for Western Europe). Logistic regression analysis suggested a higher prevalence of DRMs in 2005-2006 compared to 2004 for NNRTIs (p = .03) and, to a lesser extent, for PIs (p = .07).

Conclusion: TDR to NNRTIs was more frequent than to PIs in both geographic regions, increased over time, and was highest in North America.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Retroviral Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Resistance, Viral / genetics*
  • Europe / epidemiology
  • Female
  • Genotype
  • Geography
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology*
  • HIV Infections / virology*
  • HIV Protease / genetics
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Logistic Models
  • Male
  • Mass Screening
  • Middle Aged
  • North America / epidemiology
  • Prevalence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1