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Highly active antiretroviral therapy results in a decrease in CD8+ T cell activation and preferential reconstitution
T G Evans1, W Bonnez, H R Soucier
1Infectious Diseases Unit, University of Rochester, NY, USA.
Antiviral Research
|December 2, 1998
Summary
Highly active antiretroviral therapy (HAART) improves CD4+ T cell counts but does not restore naive CD4+ T cells. Immune activation markers decrease more than CD4+ counts, suggesting HAART impacts T cell activation significantly.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Highly active antiretroviral therapy (HAART) is known to increase CD4+ T cell counts and decrease HIV RNA levels.
- The impact of HAART on the naive CD4+ T cell compartment and CD8+ T cell activation remains unclear.
Purpose of the Study:
- To evaluate the effect of HAART on naive CD4+ T cell recovery and CD8+ T cell activation.
- To determine if absolute CD4+ T cell increases correlate with immune reconstitution.
Main Methods:
- A study involving 29 patients receiving nucleoside therapy alone or with a protease inhibitor.
- Analysis of 191 examinations over 40 weeks, measuring CD4+ T cell counts, naive/memory phenotype (CD62L/CD45RA), and CD8+ T cell activation (CD38).
Main Results:
- HAART, particularly with protease inhibitors, led to significant increases in CD4+ T cell numbers.
- The rise in CD4+ T cells was predominantly of memory phenotype, with no significant recovery in the naive CD4+ T cell compartment over 40 weeks.
- CD8+ T cell activation (CD38 expression) decreased significantly during HAART, often exceeding the magnitude of CD4+ T cell increases.
Conclusions:
- HAART induces greater changes in immune activation markers than in absolute CD4+ T cell counts.
- Immune reconstitution, specifically naive CD4+ T cell recovery, is not fully achieved with HAART within 40 weeks.
- Relying solely on CD4+ T cell counts may not accurately reflect immune competence or activation status in patients on HAART.