Rapid restoration of CD4 T cell subsets in subjects receiving antiretroviral therapy during primary HIV-1 infection

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Abstract
To compare the effect of highly active antiretroviral therapy on immune reconstitution in subjects with acute and chronic HIV-1 infection. Prospective study including 58 treatment-naive subjects who commenced indinavir or nelfinavir and two nucleosides during primary (PHI; n = 28) or chronic HIV-1 infection (CHI; n = 30). Naive (CD45RA+62L+), memory (CD45RA−) and activated (CD38+HLA-DR+) T cell subsets were quantified at 1–2 monthly time intervals using 4-colour flow cytometry. At 1 year, HIV-1 RNA declined in both cohorts to undetectable levels (< 50 copies/ml), while median CD4 lymphocyte count increased from 470 to 758 × 106 cells/l in PHI and from 204 to 310 × 106 cells/l in CHI, reaching > 500 × 106 cells/l in 93% of PHI, but only in 37% of CHI subjects (P < 0.001). Naive CD4 lymphocytes increased from 106 to 176 × 106 cells/l in PHI and from 41 to 44 × 106 cells/l in CHI (PHI versus CHI at 12 months:P = 0.003), while memory cells rose from 368 to 573 × 106 cells/l in PHI and from 148 to 223 × 106 cells/l in CHI (P < 0.001). Early increases (< 3 months) of CD4 lymphocytes were larger in subjects with PHI, consisting of naive CD45RA+CD62L+ as well as memory CD45RA−CD62L+ cells (P = 0.001). CD4 activation declined from 5 to 2% in PHI and from 13 to 6% in CHI (P = 0.001), while CD8 cell activation was reduced from 33 to 15% in PHI and from 42 to 19% in CHI (P = 0.02). Immune reconstitution was more complete, occurred earlier and comprised both naive and memory CD4 T lymphocytes in subjects who commenced antiretroviral therapy during primary HIV-1 infection.

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