Association of a pool of HIV-1 with erythrocytes in vivo: a cohort study.
BACKGROUND
Treatment of HIV-1-infected individuals with antiretrovirals can result in sustained suppression of plasma viral RNA at concentrations below the detection limit of available assays. However, continuing virus replication has been detected in patients with viral RNA in plasma suppressed for months to years, and many cell types are known to act as reservoirs or carriers for the virus. In vitro, erythrocytes bind HIV-1 immune complexes, so we tested for a circulating pool of HIV-1 associated with erythrocytes in people with HIV-1 infection.


METHODS
We investigated 82 chronically HIV-1-infected individuals. Plasma, white cells, and erythrocytes were tested for HIV-1 RNA by RT-PCR.


RESULTS
Erythrocyte-associated HIV-1 RNA was detected in 80 of 82 individuals. In 23, plasma HIV-1 RNA had been undetectable (<20 copies/mL) for up to 32 months; in corresponding erythrocyte samples, there were up to 82878 HIV-1 RNA copies per mL whole blood. HIV-1 associated with erythrocytes in vivo was shown to be infectious. Within the subgroup of patients with undetectable plasma viral load, higher numbers of HIV-1 associated with erythrocytes were correlated with a history of advanced clinical stages of HIV-1 infection (p=0.014).


CONCLUSIONS
A pool of HIV-1 is associated with erythrocytes even after long-term suppression of viral RNA in plasma. This finding is direct evidence for continuing virus replication or release in these individuals. Quantification of this viral pool may help to judge suppression of HIV-1 replication in individuals with undetectable plasma HIV-1 RNA.
Hess
Christoph
C
Department of Research, Immunonephrology Laboratory, University Hospital Basel, Basel, Switzerland. christoph.hess@unibas.ch
Klimkait
Thomas
T
Schlapbach
Luregn
L
Del Zenero
Veronika
V
Sadallah
Salima
S
Horakova
Eliska
E
Balestra
Gianmarco
G
Werder
Verena
V
Schaefer
Christoph
C
Battegay
Manuel
M
Schifferli
Jürg-Alfred
JA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004912:Erythrocytes / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012367:RNA, Viral