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. Vullo4
1University 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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