title: Mutational resistance pattern of HIV type 1 in CD14+ monocytes, CD4+ T cells, and plasma from treated patients.
abstract: It is necessary to understand the molecular nature of the virus population that persists in cellular reservoirs. To achieve this we planned to characterize the patterns of resistance of HIV-1 in CD14(+) monocytes, CD4(+) T cells, and plasma. Blood samples were collected from 42 patients treated for HIV: 32 were in virological failure and in 10 viremia was undetectable. CD14(+) and CD4(+) T cells were isolated using magnetic beads. Genotyping of the reverse transcriptase and protease gene of HIV-1 was undertaken using the fluorescent dideoxy-terminator method. Of the 32 patients in virological failure, 24 (75%) had resistance mutations in at least one compartment. The numbers and types of mutations from monocytes were the same as those detected in both CD4(+) T cell-associated virus and plasma in only 8% whereas in 71% monocytes exhibited a different mutation pattern. In 21% of patients, the profile of drug-resistant mutations in the virus from blood monocytes was identical to that in plasma but differed from that in CD4. In the 71% of patients with virological suppression, the genotypic resistance pattern differed between monocytes and CD4(+) T cells. Circulating monocytes may harbor a viral dominant population different from those viruses circulating in blood and archived in CD4(+) T cells. Hence, monocytes and other cellular reservoirs might serve as an indirect source of a drug-resistant viral variant.
authors.affiliation: Department of Experimental Medicine, Virology Section, Sapienza University of Rome and Policlinico Umberto I, Rome, Italy. ombretta.turriziani@uniroma1.it
authors.forename: Ombretta
authors.initials: O
authors.lastname: Turriziani
authors.forename: Arianna
authors.initials: A
authors.lastname: Boni
authors.forename: Francesca
authors.initials: F
authors.lastname: Falasca
authors.forename: Francesca
authors.initials: F
authors.lastname: Graziano
authors.forename: Mauro
authors.initials: M
authors.lastname: Bucci
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fantauzzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoletti
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Massetti
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Guido
authors.initials: G
authors.lastname: Antonelli
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / 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; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D009000:Monocytes / Q000737:chemistry / Q000821:virology*; D020125:Mutation, Missense; D010949:Plasma / Q000821:virology*; D017422:Sequence Analysis, DNA
chemical_list: D018950:Lipopolysaccharide Receptors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1