title: Drug-resistant variants that evolve during nonsuppressive therapy persist in HIV-1-infected peripheral blood mononuclear cells after long-term highly active antiretroviral therapy.
abstract: The aim of this study was to determine whether drug-resistant virus persists in peripheral blood mononuclear cells (PBMCs) after long-term suppression of virus replication. Proviral DNA was extracted from the PBMCs of 11 patients on long-term highly active antiretroviral therapy (HAART). Genotyping of the reverse transcriptase (RT) and protease gene of several proviral variants was performed using limiting dilution polymerase chain reaction and single-copy sequencing. All patients were on successful HAART for a mean period of 59 months but had a history of suboptimal therapy and genotypic drug resistance before. Comparison of the amino acid sequence of the RT and protease gene in the different proviral variants, with that of the plasma virus isolated before HAART treatment, revealed that the different drug-resistant viral variants that evolved during the process of gradually building up resistance were still detectable in the PBMCs in 10 of the 11 patients tested. The proportion of resistant variants was found to correlate with the time that the resistant variants had been able to replicate. These data clearly show that virus variants that are able to replicate for a certain period enter the latent reservoir and remain archived in the PBMCs for a very long period.
authors.affiliation: AIDS Reference Laboratory, Ghent University Hospital, Belgium. chris.verhofstede@ugent.be
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
authors.forename: Ann
authors.initials: A
authors.lastname: Noë
authors.forename: Els
authors.initials: E
authors.lastname: Demecheleer
authors.forename: Nancy
authors.initials: N
authors.lastname: De Cabooter
authors.forename: Filip
authors.initials: F
authors.lastname: Van Wanzeele
authors.forename: Bea
authors.initials: B
authors.lastname: Van Der Gucht
authors.forename: Dirk
authors.initials: D
authors.lastname: Vogelaers
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics*; D020539:Sequence Analysis, Protein; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease