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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Rajesh Mohey, Danmark
  • Anne Louise Jørgensen, Aalborg Universitetsbibliotek, Danmark
  • Bjarne K Møller
  • Finn T Black, Danmark
  • Jørgen Kjems
  • Niels Obel, Institut for Ortopædi og Intern Medicin, Danmark
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 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 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). 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.
OriginalsprogEngelsk
TidsskriftJournal of Clinical Virology
Vol/bind34
Nummer4
Sider (fra-til)257-267
Antal sider11
ISSN1386-6532
DOI
StatusUdgivet - 2005

Se relationer på Aarhus Universitet Citationsformater

ID: 44942667