title: Development of HIV with drug resistance after CD4 cell count-guided structured treatment interruptions in patients treated with highly active antiretroviral therapy after dual-nucleoside analogue treatment.
abstract: BACKGROUND
  For patients with human immunodeficiency virus (HIV) infection, structured treatment interruption (STI) is an attractive alternative strategy to continuous treatment, particularly in resource-restrained settings, because it reduces both side effects and costs. One major concern, however, is the development of resistance to antiretroviral drugs that can occur during multiple cycles of starting and stopping therapy.
  
  
  METHODS
  HIV genotypic drug resistance was investigated in 20 HIV-infected Thai patients treated with highly active antiretroviral therapy (HAART) and CD4 cell count-guided STI after dual nucleoside reverse-transcriptase inhibitor (NRTI) treatment. Resistance was tested at the time of the switch from dual-NRTI treatment to HAART and when HAART was stopped during the last interruption.
  
  
  RESULTS
  After STI, one major drug-resistance mutation occurred (T215Y), and, in the 4 samples with preexisting major mutations (D67N [n=2], K70R [n=2], T215Y [n=2], and T215I [n=1]), the mutations disappeared. All mutations in the HIV protease gene were minor mutations already present, in most cases, before STI was started, and their frequency was not increased through STI, whereas the frequency of reverse-transcriptase gene mutations significantly decreased after the interruptions. After the 48-week study period, no patients had virological failure. Long-term follow-up (108 weeks) showed 1 case of virological failure in the STI arm and 1 in the continuous arm. No virological failure was seen in patients with major mutations.
  
  
  CONCLUSIONS
  Major HIV drug-resistance mutations were not induced through CD4 cell count-guided treatment interruptions in HIV-infected patients successfully treated with HAART after dual-NRTI therapy.
authors.affiliation: HIV Netherlands, Australia, Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Reto
authors.initials: R
authors.lastname: Nuesch
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: Umaporn
authors.initials: U
authors.lastname: Siangphoe
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents