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Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients.
HIV Med 2004; 5(1):55-65HM

Abstract

OBJECTIVES

To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly active antiretroviral therapy (HAART).

METHODS

Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus.

RESULTS

HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/microL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/microg at baseline to a week-48 median value of 26 697 copies/microg.

CONCLUSION

Immune functional reconstitution was not achieved in these HAART naive patients.

Authors+Show Affiliations

Department of Immunology/Microbiology, Rush-Presbyterian- St. Luke's Medical Center, Chicago, IL 60612, USA. lalharth@rush.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14731171

Citation

Al-Harthi, L, et al. "Evaluation of the Impact of Highly Active Antiretroviral Therapy On Immune Recovery in Antiretroviral Naive Patients." HIV Medicine, vol. 5, no. 1, 2004, pp. 55-65.
Al-Harthi L, Voris J, Patterson BK, et al. Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients. HIV Med. 2004;5(1):55-65.
Al-Harthi, L., Voris, J., Patterson, B. K., Becker, S., Eron, J., Smith, K. Y., ... Landay, A. (2004). Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients. HIV Medicine, 5(1), pp. 55-65.
Al-Harthi L, et al. Evaluation of the Impact of Highly Active Antiretroviral Therapy On Immune Recovery in Antiretroviral Naive Patients. HIV Med. 2004;5(1):55-65. PubMed PMID: 14731171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients. AU - Al-Harthi,L, AU - Voris,J, AU - Patterson,B K, AU - Becker,S, AU - Eron,J, AU - Smith,K Y, AU - D'Amico,R, AU - Mildvan,D, AU - Snidow,J, AU - Pobiner,B, AU - Yau,L, AU - Landay,A, PY - 2004/1/21/pubmed PY - 2004/6/21/medline PY - 2004/1/21/entrez SP - 55 EP - 65 JF - HIV medicine JO - HIV Med. VL - 5 IS - 1 N2 - OBJECTIVES: To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly active antiretroviral therapy (HAART). METHODS: Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus. RESULTS: HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/microL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/microg at baseline to a week-48 median value of 26 697 copies/microg. CONCLUSION: Immune functional reconstitution was not achieved in these HAART naive patients. SN - 1464-2662 UR - https://www.unboundmedicine.com/medline/citation/14731171/Evaluation_of_the_impact_of_highly_active_antiretroviral_therapy_on_immune_recovery_in_antiretroviral_naive_patients_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1464-2662&amp;date=2004&amp;volume=5&amp;issue=1&amp;spage=55 DB - PRIME DP - Unbound Medicine ER -