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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.
J Clin Virol 2005; 34(4):257-67JC

Abstract

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.

STUDY DESIGN

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.

Authors+Show Affiliations

Department of Infectious Diseases, Skejby University Hospital, Aarhus, Denmark. mohey@dadlnet.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16286049

Citation

Mohey, Rajesh, et al. "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." Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, vol. 34, no. 4, 2005, pp. 257-67.
Mohey R, Jørgensen LB, Møller BK, et al. 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. J Clin Virol. 2005;34(4):257-67.
Mohey, R., Jørgensen, L. B., Møller, B. K., Black, F. T., Kjems, J., & Obel, N. (2005). 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. Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, 34(4), pp. 257-67.
Mohey R, et al. 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. J Clin Virol. 2005;34(4):257-67. PubMed PMID: 16286049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mohey,Rajesh, AU - Jørgensen,Louise B, AU - Møller,Bjarne K, AU - Black,Finn T, AU - Kjems,Jørgen, AU - Obel,Niels, Y1 - 2005/04/18/ PY - 2005/02/04/received PY - 2005/02/11/accepted PY - 2005/11/16/pubmed PY - 2005/12/31/medline PY - 2005/11/16/entrez SP - 257 EP - 67 JF - Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology JO - J. Clin. Virol. VL - 34 IS - 4 N2 - 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. STUDY DESIGN: 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. SN - 1386-6532 UR - https://www.unboundmedicine.com/medline/citation/16286049/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1386-6532(05)00087-9 DB - PRIME DP - Unbound Medicine ER -