Genotypic resistance of archived and circulating viral strains in the blood of treated HIV-infected individuals.
The aim of this study was to evaluate patterns of antiretroviral resistance of HIV-1 in peripheral blood mononuclear cells (PBMCs) and in the plasma of patients whose therapeutic regimen is failing. Plasma and PBMC samples were collected from 95 HIV-infected patients undergoing long-term treatment. Genotyping of the reverse transcriptase (RT) and protease genes of HIV-1 was undertaken using the fluorescent dideoxy-terminator method. Comparison of the amino acid sequence of the RT and protease genes in cell-associated variants of HIV-1 with that of the plasma revealed that 62 of the 95 patients' samples tested exhibited different genotypic resistance patterns (discordant samples [DSs]). In 27% of samples, the patterns of resistance detected were concordant in both compartments. In 51% of DSs, the greatest number of mutations was found in plasma; however, in 37% of DSs, greater numbers of mutations were found in PBMC DNA. The HIV mutation patterns detected in plasma do not necessarily reflect those found in the cell-associated compartment. The observation that the cellular compartment may contain an archive of the resistance variant makes this reservoir an interesting substrate for analysis of the "resistance potential" in a given patient.
Turriziani
Ombretta
O
Virology Section, Department of Experimental Medicine, Policlinico Umberto I, University La Sapienza, Viale di Porta Tiburtina 28, 00185 Rome, Italy. ombretta.turriziani@uniroma1.it
Bucci
Mauro
M
Stano
Armando
A
Scagnolari
Carolina
C
Bellomi
Francesca
F
Fimiani
Caterina
C
Mezzaroma
Ivano
I
D'Ettorre
Gabriella
G
Brogi
Andrea
A
Vullo
Vincenzo
V
Antonelli
Guido
G
D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005814:Genes, Viral; 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* / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D014766:Viremia / Q000821:virology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease