Persistence of distinct HIV-1 populations in blood monocytes and naive and memory CD4 T cells during prolonged suppressive HAART.
OBJECTIVE
Reservoirs of HIV-1 are a major obstacle to virus eradication. There is therefore a need to clearly understand the molecular nature of the virus populations that persist in patients with sustained suppression of plasma viraemia on highly active antiretroviral therapy (HAART).


METHODS
We performed a detailed analysis of the genotypes of HIV-1 quasispecies isolated from highly purified blood cell types taken from three selected patients with sustained undetectable viral loads on HAART for 7 years.


METHODS
We used polychromatic flow cytometry to sort naive and memory CD4 T cells, CD14 monocytes, and CD56+CD3- natural killer (NK) cells from the total peripheral blood mononuclear cells after 7 years of HAART. Clonal analysis was used to determine coreceptor use and drug-resistance genotypes of HIV-1 quasispecies in the sorted blood cell types.


RESULTS
We detected HIV-1 DNA in memory and naive CD4 T cells and in CD14 monocytes, but not in the CD56+CD3- NK cells. Phylogenetic analysis demonstrated that the various blood cells types of two of the three patients harboured genetically distinct HIV-1 quasispecies. Drug-resistance mutations were also distributed differently from one cell type to another. This compartmentalization suggests a minimal virus trafficking between blood cell types during suppressive HAART.


CONCLUSIONS
We observed a cell-specific compartmentalization of the residual virus populations during prolonged suppressive HAART. The coexistence of numerous HIV-1 quasispecies with different resistance genotypes and coreceptor use in cellular reservoirs may be relevant for future antiretroviral treatment strategies.
Delobel
Pierre
P
Laboratory of Virology EA2046-IFR30, Toulouse University Hospital, France.
Sandres-Sauné
Karine
K
Cazabat
Michelle
M
L'Faqihi
Fatima-Ezzahra
FE
Aquilina
Christian
C
Obadia
Martine
M
Pasquier
Christophe
C
Marchou
Bruno
B
Massip
Patrice
P
Izopet
Jacques
J
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004197:Disease Reservoirs; D024882:Drug Resistance, Viral; D005434:Flow Cytometry; D015752:Genes, env / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4