Abstract

Impact of raltegravir on immune reconstitution and thymopoiesis in HIV-1-infected patients with undetectable viremia on HAART

Presented by Carolina Garrido (Spain).

C. Garrido, N. Rallon, N. Zahonero, M. López, V. Soriano, C. de Mendoza, J.M. Benito

Hospital Carlos III, Infectious Diseases, Madrid, Spain

Background: CD4 gains under antiretroviral treatment might result from cells recently migrated from the thymus or from cells proliferating in the periphery. CD31 on the surface of CD4⁺T-cells has shown to identify recent thymic-emigrants. We characterized CD4⁺T-cell gains in patients switching to a RAL-containing regimen.
Methods: Patients on HAART with long-term suppressed viremia were identified and split out into two groups: 1) switch to RAL and 2) maintain the same regimen (control). Samples were collected at the time of RAL-switch (0) and 6 months after (+6). Immune parameters were assessed in PBMCs using 5-color flow cytometry. Analysis of naive and memory CD4⁺T-cells (CD45RA and CD27) was combined with measurement of activation (CD38) and CD31 expression. Results were reported as median [IQR] and comparisons were performed with Mann-Whitney tests.
Results: 37 patients were examined, 19 on RAL and 18 controls. Baseline characteristics did not differ among groups for CD4⁺T-cells (322 cells/µL [204-499]) and percentage (18% [12.5-26.5]), age (44 years-old [41.5-48]) and time with suppressed viremia (2.12 years [0.84-4.80]).
Six months after RAL-switch, CD4⁺T-cells were significantly higher compared to baseline (448 [288-575] vs 322 [242-594] cells/µL, p=0.026), while controls kept stable CD4 values (330 [176-425] vs 312 [141-478], p=0.813).
No differences were observed from 0 to +6 in any group for immune activation or CD31 expression. However, the proportion of naive CD4⁺T-cells increased in the RAL group after switch from 18.2% [9.3-29.3] to 23.7% [12.7-31.4] (p=0.014), while effector memory CD4⁺T-cells significantly declined from 13.3% [9-21.3] to 10.2% [5.5-16.8] (p=0.005). All these subsets remained stable in controls.
Conclusions: Switching to a RAL-containing regimen resulted in significant CD4⁺T-cell gains compared to keep the same HAART regimen in patients with undetectable viremia. This increase is mainly driven by enrichment of CD4 naive cells, which do not result from increased thymic function, suggesting that peripheral expansion accounts for this observation.
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