title: HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial. The National Virology Groups. Delta Virology Working Group and Coordinating Committee.
abstract: BACKGROUND
  The Delta trial showed that combination therapy (zidovudine plus didanosine and zidovudine plus zalcitabine) substantially lengthened life and reduced disease progression compared with zidovudine monotherapy. We did a nested virological study in three countries (France, the Netherlands, and the UK) to investigate changes in markers for viral load and antiretroviral-drug resistance during therapy.
  
  
  METHODS
  240 zidovudine-naive HIV-1-infected patients were randomly assigned zidovudine only (n = 87), zidovudine plus didanosine (n = 80), or zidovudine plus zalcitabine (n = 73). Viral load in peripheral-blood mononuclear cells and plasma was measured by quantitative culture. Plasma HIV-1 RNA was measured by reverse-transcriptase PCR amplification, and serum p24 antigen by ELISA. Resistance to antiretroviral drugs was measured phenotypically by culture and genotypically by detection and quantification of drug-related point mutations in the pol gene. Analyses were done by intention to treat.
  
  
  RESULTS
  The reduction in viral load was greatest 4-12 weeks after the start of therapy and was most pronounced in the combination-therapy study groups (median reductions of RNA at 4 weeks 1.58, 1.28, and 0.49 log10 copies/mL for zidovudine plus didanosine, zidovudine plus zalcitabine, and zidovudine only, respectively). RNA levels at 8 weeks were predictive of disease progression and death after allowance for baseline values. At 48 weeks, the proportion of participants with phenotypic zidovudine resistance was similar in all three groups: didanosine and zalcitabine resistance were rare; zidovudine genomic resistance correlated with phenotypic resistance (r = 0.54, p < 0.0001) and developed earlier in the combined-therapy groups. However, participants in the zidovudine monotherapy group had higher circulating loads of resistant virus than those in the combined-therapy groups.
  
  
  CONCLUSIONS
  Combined antiretroviral therapy was more efficient at lowering virus load than monotherapy. Although zidovudine resistance was common in monotherapy and combined-therapy groups, circulating concentrations of resistant virus were substantially lower in the combination groups, which is likely to be a result of the continued antiviral activity of didanosine or zalcitabine.
authors.affiliation: Hôpital-Bichat-Claude Bernard, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: C
authors.initials: C
authors.lastname: Boucher
authors.forename: C
authors.initials: C
authors.lastname: Loveday
authors.forename: D
authors.initials: D
authors.lastname: Descamps
authors.forename: V
authors.initials: V
authors.lastname: Fauveau
authors.forename: J
authors.initials: J
authors.lastname: Izopet
authors.forename: D
authors.initials: D
authors.lastname: Jeffries
authors.forename: S
authors.initials: S
authors.lastname: Kaye
authors.forename: C
authors.initials: C
authors.lastname: Krzyanowski
authors.forename: A
authors.initials: A
authors.lastname: Nunn
authors.forename: R
authors.initials: R
authors.lastname: Schuurman
authors.forename: J M
authors.initials: JM
authors.lastname: Seigneurin
authors.forename: C
authors.initials: C
authors.lastname: Tamalet
authors.forename: R
authors.initials: R
authors.lastname: Tedder
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: G J
authors.initials: GJ
authors.lastname: Weverling
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D015751:Genes, pol / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D017354:Point Mutation; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019562:Viral Load; D016047:Zalcitabine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine