Artikel
Stable percentages of CD4+ T-cells and lower levels of soluble CD25 in elite controllers, but not intermediate controllers of HIV-1 replication
Konstante prozentuale CD4+ T-Zellen und niedrigere Spiegel an löslichem CD25 in Elite Kontrollern im Vergleich zu intermediate Kontrollern
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Veröffentlicht: | 2. Juni 2010 |
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Background: The objective was to determine whether there is a non-detrimental level of plasma viremia (pVL) in Long-Term Nonprogressors (LTNP) and to explore immune correlates of protection such as, HIV-encoding defective nef-variants or a characteristic cytokine profile against disease progression.
Methods: 31 patients from a database of more than 6000 patients met the definition of Elite Controller (EC, n=18) or Intermediate Controller (IC, n=13). We defined 2 groups. EC: CD4+ T-cells ≥500/uL, pVL < 50 copies/mL. IC: CD4+ T-cells ≥500/uL, pVL 50–2000 copies/mL. Analyses of nef-modifications of HIV by nef sequencing and chemokine/cytokine profile in plasma using the 25plex Luminex technology were additionally performed.
Results: Median time since HIV-diagnosis was 11 years [2–17] and 3.5 years [2–10.5] for EC and IC, respectively. At baseline, median CD4+ T-cells did not significantly differ between groups. CD4+ T-cell counts and percentage were 880/µl and 39% [576-1056, 34-41%] vs. 762/µl and 37% [562–983, 31–43%] in EC and IC, respectively. We observed a significant decrease of CD4+ T-cell percentage (38% [29–41] vs. 31% [28–34]; p=0.0002) in IC – but not in EC – over time. Nef sequencing showed in both groups mainly mutations in regions important for MHCI down regulation and/or retention, possibly resulting in a more efficient peptide presentation to CD8+ T-cell. Moreover, we found in plasma of EC significant lower levels of soluble (s) CD25 (p<0.05) as well as slightly lower levels of IL12 and CXCL9 (MIG).
Conclusions: In ECs, the percentage of CD4+ T-cell remains stable with long-term follow-up. The small, but significant, decrease in the percentage of CD4+ T-cells in IC seems to be related to HIV replication. Lower levels of sCD25 in EC might be explained by an inhibition of CD25 shedding from CD4+ T- cells which could be responsible for a better T cell proliferation. We conclude that there is no “safe” level of HIV replication.