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Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART.
J Clin Virol. 2005 Jul; 33(3):206-16.JC

Abstract

BACKGROUND

HIV drug resistance mutations both in peripheral blood mononuclear cells (PBMCs) and plasma have the ability to influence the outcome of highly active antiretroviral therapy for HIV patients. PBMCs harbor archival proviral DNA, are a major source of HIV and also underdo latent infection during suppressive HAART.

OBJECTIVES

The main objectives of this study were to assess whether specific viral load groups are better predictors of drug resistance and to examine the utility of PBMCs for drug resistance testing during HAART.

STUDY DESIGN

Patients were grouped into a plasma panel comprising of 100 patients and a PBMC/plasma panel of 45 patients. These two groups were further divided according to plasma viral load (low, medium and high). Therapy naive patients were also included. Resistance to protease and reverse transcriptase inhibitors was assessed in each group over different viral load categories.

RESULTS

Our data indicated that in addition to plasma, PBMCs also are a reliable predictor of drug resistance. Drug resistance mutations analyzed from each panel demonstrated that intermediate and high viral loads were strong indicators of drug resistance in both the plasma and PBMC compartments. Despite this, a significant portion of patients with high viral loads showed reduced levels of drug resistance indicating that factors including poor compliance, drug pharmacokinetics and host genetic factors are also likely to contribute to therapy failure. A significant degree of resistance to NRTI and PI resistance was found in treatment-naive individuals, demonstrating the transmission of circulating drug resistant HIV-1 variants.

CONCLUSIONS

Our data emphasize the need for stronger pharmacokinetic evaluation during HAART, especially for patients with intermediate or high plasma viremia. The utility of PBMCs as an alternative source of resistance profiling was also demonstrated, and this approach may benefit the assessment of future drug regimens for HIV-infected patients.

Authors+Show Affiliations

Center for Infectious Diseases and Microbiology Laboratory Systems, ICPMR, Westmead Hospital, Westmead, NSW 2145, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15911442

Citation

Chew, Choo Beng, et al. "Assessment of Drug Resistance Mutations in Plasma and Peripheral Blood Mononuclear Cells at Different Plasma Viral Loads in Patients Receiving HAART." Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, vol. 33, no. 3, 2005, pp. 206-16.
Chew CB, Potter SJ, Wang B, et al. Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART. J Clin Virol. 2005;33(3):206-16.
Chew, C. B., Potter, S. J., Wang, B., Wang, Y. M., Shaw, C. O., Dwyer, D. E., & Saksena, N. K. (2005). Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART. Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, 33(3), 206-16.
Chew CB, et al. Assessment of Drug Resistance Mutations in Plasma and Peripheral Blood Mononuclear Cells at Different Plasma Viral Loads in Patients Receiving HAART. J Clin Virol. 2005;33(3):206-16. PubMed PMID: 15911442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART. AU - Chew,Choo Beng, AU - Potter,Simon J, AU - Wang,Bin, AU - Wang,Yuan Min, AU - Shaw,Chanh Op, AU - Dwyer,Dominic E, AU - Saksena,Nitin K, Y1 - 2004/12/24/ PY - 2004/08/11/received PY - 2004/11/03/accepted PY - 2005/5/25/pubmed PY - 2005/7/27/medline PY - 2005/5/25/entrez SP - 206 EP - 16 JF - Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology JO - J Clin Virol VL - 33 IS - 3 N2 - BACKGROUND: HIV drug resistance mutations both in peripheral blood mononuclear cells (PBMCs) and plasma have the ability to influence the outcome of highly active antiretroviral therapy for HIV patients. PBMCs harbor archival proviral DNA, are a major source of HIV and also underdo latent infection during suppressive HAART. OBJECTIVES: The main objectives of this study were to assess whether specific viral load groups are better predictors of drug resistance and to examine the utility of PBMCs for drug resistance testing during HAART. STUDY DESIGN: Patients were grouped into a plasma panel comprising of 100 patients and a PBMC/plasma panel of 45 patients. These two groups were further divided according to plasma viral load (low, medium and high). Therapy naive patients were also included. Resistance to protease and reverse transcriptase inhibitors was assessed in each group over different viral load categories. RESULTS: Our data indicated that in addition to plasma, PBMCs also are a reliable predictor of drug resistance. Drug resistance mutations analyzed from each panel demonstrated that intermediate and high viral loads were strong indicators of drug resistance in both the plasma and PBMC compartments. Despite this, a significant portion of patients with high viral loads showed reduced levels of drug resistance indicating that factors including poor compliance, drug pharmacokinetics and host genetic factors are also likely to contribute to therapy failure. A significant degree of resistance to NRTI and PI resistance was found in treatment-naive individuals, demonstrating the transmission of circulating drug resistant HIV-1 variants. CONCLUSIONS: Our data emphasize the need for stronger pharmacokinetic evaluation during HAART, especially for patients with intermediate or high plasma viremia. The utility of PBMCs as an alternative source of resistance profiling was also demonstrated, and this approach may benefit the assessment of future drug regimens for HIV-infected patients. SN - 1386-6532 UR - https://www.unboundmedicine.com/medline/citation/15911442/Assessment_of_drug_resistance_mutations_in_plasma_and_peripheral_blood_mononuclear_cells_at_different_plasma_viral_loads_in_patients_receiving_HAART_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1386-6532(04)00337-3 DB - PRIME DP - Unbound Medicine ER -