Mutational resistance pattern of HIV type 1 in CD14+ monocytes, CD4+ T cells, and plasma from treated patients.
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.
Turriziani
Ombretta
O
Department of Experimental Medicine, Virology Section, Sapienza University of Rome and Policlinico Umberto I, Rome, Italy. ombretta.turriziani@uniroma1.it
Boni
Arianna
A
Falasca
Francesca
F
Graziano
Francesca
F
Bucci
Mauro
M
D'Ettorre
Gabriella
G
Fantauzzi
Alessandra
A
Paoletti
Francesca
F
Massetti
Anna Paola
AP
Mezzaroma
Ivano
I
Antonelli
Guido
G
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
D018950:Lipopolysaccharide Receptors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1