HIV-1 can persist in aged memory CD4+ T lymphocytes with minimal signs of evolution after 8.3 years of effective highly active antiretroviral therapy.
BACKGROUND
Patients on long-term highly active antiretroviral therapy (HAART) were studied to determine persistence, drug resistance development, and evolution of HIV-1 proviral DNA.


METHODS
Peripheral blood mononuclear cells were obtained by large volume blood drawn (500 mL) from 8 clinically successfully treated patients who had received uninterrupted HAART for up to 8.9 years. HIV-1 load was determined by Taqman real-time polymerase chain reaction. Drug resistance mutations were determined by sequencing and ultrasensitive, allele-specific, reverse transcriptase (RT)-polymerase chain reaction.


RESULTS
HIV-1 DNA load was significantly higher in aged memory (CD45RO CD57) when compared with memory (CD45RO CD57) and naive (CD27 CD45RO) CD4 T cells after HAART. Sequencing revealed no major drug resistance mutations in protease in all patients and appearance of resistance mutations in RT in just 1 patient. In 1 of 5 patients with undetectable viremia during treatment, RT M184 substitutions were detected. Phylogenetic analysis showed short genetic distances between patient sequences.


CONCLUSIONS
During long-term HAART, HIV-1 is able to persist in terminally differentiated CD4 T cells as proviral DNA. Viral evolution was restricted, and in 80% of the patients with undetectable viremia, no sign of viral replication could be detected.
Nottet
Hans S L M
HS
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. h.s.l.m.nottet@umcutrecht.nl
van Dijk
Sabine J
SJ
Fanoy
Ewout B
EB
Goedegebuure
Irma W
IW
de Jong
Dorien
D
Vrisekoop
Nienke
N
van Baarle
Debbie
D
Boltz
Valerie
V
Palmer
Sarah
S
Borleffs
Jan C C
JC
Boucher
Charles A B
CA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D016922:Cellular Senescence; D004279:DNA, Viral / Q000097:blood; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D009154:Mutation; D010802:Phylogeny; D013997:Time Factors
D004279:DNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1