title: Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database.
abstract: BACKGROUND
  Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce.
  
  
  METHODS
  Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease (PR) and reverse transcriptase (RT) from ARV-naïve and treated patients were sequenced.
  
  
  RESULTS
  Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. Within RT, they were M184V, Q151M, V111I and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naïve patients.
  
  
  CONCLUSIONS
  Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection.
authors.affiliation: Université Catholique de Louvain, AIDS Reference Laboratory, Avenue Hippocrate 54 -5492, 1200 Bruxelles, Belgium. jean.ruelle@uclouvain.be
authors.forename: Jean
authors.initials: J
authors.lastname: Ruelle
authors.forename: François
authors.initials: F
authors.lastname: Roman
authors.forename: Anne-Thérèse
authors.initials: AT
authors.lastname: Vandenbroucke
authors.forename: Christine
authors.initials: C
authors.lastname: Lambert
authors.forename: Katrien
authors.initials: K
authors.lastname: Fransen
authors.forename: Fedoua
authors.initials: F
authors.lastname: Echahidi
authors.forename: Denis
authors.initials: D
authors.lastname: Piérard
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
authors.forename: Marie-Luce
authors.initials: ML
authors.lastname: Delforge
authors.forename: Dolorès
authors.initials: D
authors.lastname: Vaira
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Schmit
authors.forename: Patrick
authors.initials: P
authors.lastname: Goubau
mesh_terms: D000328:Adult; D000354:Africa, Western / Q000208:ethnology; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001530:Belgium / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015498:HIV-2 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008189:Luxembourg / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000737:chemistry; D012042:Registries; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease