Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1,000 copies/ml.
BACKGROUND
Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Sub-optimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1,000 copies/ml) on mutation genesis and incorporation of resistant forms in the long-lived CD4(+) T cellular DNA compartment is not clear.


OBJECTIVE
To investigate the relationship between lamivudine associated mutant-type 184 V and the wild-type 184 M proviral forms in the circulating CD4(+) T cells of patients and low-level viremia.


METHODS
Cross-sectional study of 50 patients on long-term HAART, with a viremia of less than 1 000 copies/ml. Patients were stratified into three groups; on lamivudine, group I (viral load <20 copies/ml), group II (viral load 20-1000 copies/ml) and as lamivudine experienced, group III (viral load <1000 copies/ml). 184 M and 184 V proviral HIV-1 was detected and quantified by a specific and sensitive assay combining a TaqMan real-time PCR analysis with the amplification-refractory mutation system (ARMS) principle.


RESULTS
Fifty-six percent of patients with low-level viremia had 184 V in the CD4(+) T cellular DNA compartment as compared to only 8% in those with undetectable viremia. The presence of 184 V was significantly associated with a higher viral load (P=0.001). Patients with low-level viremia without 184 V in the CD4(+) T cellular DNA compartment, had a median plasma viral load of 135 copies/ml, while patients harbouring 184 V had a median viral load of 498 copies/ml (P=0.006). No significant differences between the groups were observed in proviral HIV-1 DNA load.


CONCLUSIONS
The frequency of the 184 V mutation was significantly lower, in the CD4(+) T cellular compartment of patients with a viral load of less than 20 copies/ml as compared to patients with a viremia of 20-1,000 copies/ml. Viremia, sustained below 20 copies/ml may prevent the appearance of 184 V mutation in this reservoir and therefore should be the objective of treatment.
Mohey
Rajesh
R
Department of Infectious Diseases, Skejby University Hospital, Aarhus, Denmark. mohey@dadlnet.dk
Jørgensen
Louise B
LB
Møller
Bjarne K
BK
Black
Finn T
FT
Kjems
Jørgen
J
Obel
Niels
N
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000302:isolation & purification*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011533:Proviruses / Q000302:isolation & purification*; D014766:Viremia / Q000188:drug therapy / Q000821:virology*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D019259:Lamivudine