, Volume 25, Issue 2, pp 106-115

Lower CD4+ T Lymphocyte Nadirs May Indicate Limited Immune Reconstitution in HIV-1 Infected Individuals on Potent Antiretroviral Therapy: Analysis of Immunophenotypic Marker Results of AACTG 5067

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Abstract

Background: Although initiation of potent antiretroviral therapy (ART) has significantly improved immune perturbations in individuals with AIDS, it is unclear which factors are most important in determining the degree of immune reconstitution.

Methods: Whole blood was analyzed at baseline and week 12 in six groups of subjects (n = 81): those with acute or following immune reconstitution after Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia (PcP) (two groups) and cytomegalovirus (CMV) retinitis (two groups), HIV-infection without AIDS (one group), and healthy volunteers (one group). Absolute CD4+ and CD8+ T lymphocytes, naíve (CD45RA+) and memory (CD45RO+) CD4+ T lymphocytes and percentages of activated CD8+ T lymphocytes (CD8+/CD38+/HLA-DR), and CD28 expression on CD4+ and CD8+ T lymphocytes were enumerated.

Results: The reconstituted CMV group, which had a history of a lower CD4+ T lymphocyte nadir compared to the reconstituted PcP group (15 cells/mm3 versus 48 cells/mm3; p = .013), had significantly lower absolute CD4+, CD8+ and naíve CD4+ T lymphocytes and a trend toward lower memory CD4+ T lymphocytes compared to the reconstituted PcP group. Moreover, no difference was noted between the reconstituted groups in the proportion of subjects with undetected HIV-1 RNA. The reconstituted subjects had significantly lower absolute CD4+, memory CD4+ and naíve CD4+ T lymphocytes than the HIV-positive controls and a significantly higher percentage of activated CD8+ T lymphocytes with a lower percentage of CD8+CD28 expression than the HIV-negative controls.

Conclusion: The association of CD4+ T lymphocyte nadir with the extent of immune reconstitution in HIV-infected individuals suggests that HIV-1 may cause irreparable immune system damage despite potent ART.