Detection and quantification of proviral HIV-1 184M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1000 copies/ml

作者：Mohey R^*; Jorgensen LB; Moller BK; Black FT; Kjems J; Obel N

来源：Journal of Clinical Virology, 2005, 34(4): 257-267.

DOI：10.1016/j.jcv.2005.02.015

• CD4(+) T compartment
• HIV drug resistance mutations
• viral load
• low-level viremia
• anti-retroviral therapy

Background: Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Suboptimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1000 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 184V and the wild-type 184M proviral forms in the circulating CD4(+) T cells of patients and low-level viremia. Study design: Cross-sectional study of 50 patients on long-term HAART, with a viremia of less than 1000 copies/ml. Patients were stratified into three groups; on lamivudine, group 1 (viral load <20 copies/ml), group II (viral load 20-1000 copies/ml) and as lamivudine experienced, group III (viral load < 1000 copies/ml). 184M and 184V 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 184V in the CD4(+) T cellular DNA compartment as compared to only 8% in those with undetectable viremia. The presence of 184V was significantly associated with a higher viral load (P = 0.001). Patients with low-level viremia without 184V in the CD4(+) T cellular DNA compartment, had a median plasma viral load of 135 copies/ml, while patients harbouring 184V 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 184V 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 20-1000 copies/ml. Viremia, sustained below 20 copies/ml may prevent the appearance of 184V mutation in this reservoir and therefore should be the objective of treatment.

• 出版日期2005-12