title: Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010.
abstract: BACKGROUND
  The selection of antiretroviral (ARV) drugs for treatment of HIV-1 infection is based on several factors including potency, toxicity, resistance and ease of administration. Emtricitabine (FTC) or lamivudine (3TC), components of recommended initial ARV regimens, are structurally related and share the same resistance mutation (M184V/I). However they differ with respect to potency and incidence of M184V/I.
  
  
  METHODS
  Resistance-associated mutation (RAM) prevalence data were obtained from genotype test results performed in a large reference laboratory from 2003-2010; subsets of data were defined by mutation pattern to resemble those following failure of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination therapy. Mutational trend data were compared to contemporaneous ARV prescription information.
  
  
  RESULTS
  In the unfiltered data set (n=107,231), the prevalence in 2010 decreased compared to 2003 for all nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs, such as M184V/I (44.0% to 17.9%), T215Y (22.7% to 4.1%), and K65R (4.3% to 2.1%). Among samples resembling those typical of first-line NNRTI-based failures, prevalence of K103N increased slightly, but prevalence of M184V/I decreased (49.8% to 36.8%), as did other NRTI RAMs. These decreases were coincident with a shift in ARV prescriptions away from zidovudine and 3TC towards tenofovir and FTC, and an increase in use of fixed-dose combinations.
  
  
  CONCLUSIONS
  RAM prevalence decreased substantially since 2003 among samples submitted for resistance testing in the US. The causes of this decrease are multifactorial, but our results suggest a possible role of increased use of potent ARVs that are available as fixed-dose combinations or as single-tablet regimens.
authors: Gilead Sciences, Inc., Foster City, CA, USA. Michael.Miller@gilead.com
authors: Michael D
authors: MD
authors: Miller
authors: Mojgan
authors: M
authors: Haddad
authors: Cathy
authors: C
authors: Su
authors: Craig
authors: C
authors: Gibbs
authors: Damian J
authors: DJ
authors: McColl
authors: Bill
authors: B
authors: Guyer
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068698:Tenofovir; D017211:Treatment Failure; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000068679:Emtricitabine; D000225:Adenine