HIV-1 Biological Phenotype and the Development of Zidovudine Resistance in Relation to Disease Progression in Asymptomatic Individuals During Treatment

AIDS. 1992 Nov;6(11):1259-64. doi: 10.1097/00002030-199211000-00003.

Abstract

Objective: To determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals.

Methods: Twenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction.

Results: Progression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P < 0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations.

Conclusions: Conversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance.

MeSH terms

  • Cytopathogenic Effect, Viral
  • Drug Resistance, Microbial / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / etiology
  • HIV Infections / microbiology
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation
  • Phenotype
  • RNA-Directed DNA Polymerase / genetics
  • Time Factors
  • Zidovudine / therapeutic use*

Substances

  • Zidovudine
  • RNA-Directed DNA Polymerase