The lymphocyte HIV reservoir in patients on long-term HAART is a memory of virus evolution.
OBJECTIVE
To investigate the dynamics of the lymphocyte HIV reservoir in patients on prolonged and effective highly active antiretroviral therapy (HAART).


METHODS
Nine HAART-treated patients were selected on the basis of long-term infection and long-term undetectable plasma viral RNA. Five patients had received antiretroviral therapy before HAART. We compared a polymorphic region of the env gene (C2V4), and the part of the pol gene encoding the reverse transcriptase in pre-HAART plasma and in the reservoir lymphocytes during HAART; the first plasma sample taken after structured treatment interruption was also studied in three patients.


METHODS
Both regions of interest were amplified from plasma HIV RNA and cellular proviral DNA, then cloned, sequenced and subjected to phylogenetic analysis.


RESULTS
Diversity of the lymphocyte reservoir was found in six of nine patients. Archiving of pre-HAART plasma clones was observed in six of nine patients. 'Wild-type' and zidovudine-resistant strains co-existed in reservoir T cells of two pre-HAART treated patients. In three patients, no resistant virus was found in the T-cell reservoir despite the detection of resistant virus in pre-HAART plasmas. However, virus archiving was documented in two of these three patients on the basis of C2V4 analysis. Latently infected T cells only partly accounted for the plasma viral load rebound after structured treatment interruption.


CONCLUSIONS
The HIV lymphocyte reservoir is dynamic. Its diversity results mainly from successive archiving of circulating plasma viruses during the course of HIV infection. Archiving of resistant virus must be taken into account in therapeutic decisions.
Lambotte
Olivier
O
INSERM E-109, Faculté de Médecine de Bicêtre, Université Paris XI, France.
Chaix
Marie-Laure
ML
Gubler
Brigitte
B
Nasreddine
Nadine
N
Wallon
Christine
C
Goujard
Cécile
C
Rouzioux
Christine
C
Taoufik
Yassine
Y
Delfraissy
Jean-François
JF
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002908:Chronic Disease; D004197:Disease Reservoirs; D024882:Drug Resistance, Viral; D015752:Genes, env / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics; D017423:Sequence Analysis, RNA; D014779:Virus Replication
D012367:RNA, Viral