Abstract

Residual HIV replication in the gut of aviremic treated individuals correlates with persistent immune activation and increased plasma levels of LPS

G. d'Ettorre¹, M. Andreotti², M. Paiardini³, L. Zaffiri⁴, G. Ceccarelli⁴, M.C. Rizza⁴, S. Vella², C.M. Mastroianni⁵, G. Silvestri³, V. Vullo<sup>4

1</sup>University of Rome Sapienza, Tropical and Infectious Diseases, Rome, Italy, ²ISS, Department of Drugs, Rome, Italy, ³University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia, United States, ⁴'Sapienza' University, Department of Tropical and Infectious Diseases, Roma, Italy, ⁵'Sapienza' University - Polo Pontino, Department of Infectious Diseases, Latina, Italy

Background: Residual virus replication in the gut and persistent microbial translocation may be involved in the chronic immune activation observed in HIV-infected individuals treated with antiretroviral therapy (ART).
Our aim was to investigate the relationship between cell-associated HIV-DNA load both in the gut and blood, plasma levels of LPS, and T cell activation during chronic HIV infection.
Methods: We studied 22 HIV-infected individuals (14 aviremic ART-treated patients and 8 ART-naive) and 10 uninfected controls. HIV-DNA load was measured by RT-PCR in blood and recto-colon biopsies. T-cell activation was measured by flow cytometry as CD38 expression. LPS was measured by Limulus assay.
Results: HIV-DNA loads (cp/10⁶PBMC) were more elevated in the gut samples than in the peripheral blood (115,3+22.28 vs 83.91+ 31.45) (p< 0.05), and correlated directly with the plasma levels of LPS (p< 0.002). In addition we found, in the group of treated patients with undetectable HIV-RNA (< 20 copies/ml) a direct correlation between the status of immune activation measured by LPS and CD38 and the amount of HIV-DNA in the gut (p< 0.0008; p< 0.0035). Finally the levels of LPS in the group of treated patients are higher than controls (p< 0.005).
Conclusions: These findings suggest that, in ART-treated HIV-infected individuals, a persistent status of immune activation and microbial translocation is associated with residual viral replication in the gut.
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