Study of Recovery of Intestinal CD4+ and Th17 T Cells in HIV-infected Individuals on Short-term Antiretroviral Therapy

Study of Recovery of Intestinal CD4+ and Th17 T Cells in HIV-infected Individuals on Short-term Antiretroviral Therapy

HIV Infection and Gut Mucosal Immune Function: Longitudinal Analyses of Intestinal CD4+ and Th17 T Cells in HIV-infected Individuals on Short-term Antiretroviral Therapy

HIV infection is associated with a state of chronic, generalized immune activation that has been shown in many studies to be a key predictor of progression to AIDS. The molecular, cellular, and pathophysiological mechanisms underlying the HIV-associated immune activation are complex and still poorly studied. There is, however, growing consensus that both viral and host factors contribute to this phenotype, with emphasis on the role played by the mucosal immune dysfunction (and consequent microbial translocation). Moreover if it is known that in HIV-infected individuals, a severe depletion of intestinal cluster of differentiation 4 (CD4+) T-cells, is associated with loss of epithelium integrity, microbial translocation and systemic immune activation, the kinetics of intestinal CD4+ T-cell reconstitution under combined antiretroviral therapy (cART) remains poorly understood. This study sought to evaluate the reconstitution of intestinal CD4+ T-cells, including Th1 and Th17, in blood and colon samples collected from HIV-infected individuals before and after a short term cART.

HIV infection, GUT, microbial translocation, chronic inflammation, antiretroviral therapy, cART, HAART, Th17, Th1, CD4+

patients naïve for antiretroviral treatment that met the criteria to start cART according to International Guidelines. These patients will be studied for primary and secondary outcomes after a short term antiretroviral therapy.

Conventional antiretroviral therapy started in naïve patients for antiretroviral treatment that met the criteria to start cART according to International Guidelines. The antiretroviral treatment consisted in a tenofovir-emtricitabine NRTI backbone (TDF/FTC, 300/200 mg/ml, once a day) plus boosted protease inhibitor, lopinavir/ritonavir (LPV/r, 400/100 mg twice a day) or darunavir/ritonavir (DRV/r 800/100mg once a day).

Difference of number of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in colon samples between T0 (before start of cARV) and T1 (after 6 months of cARV)

Difference of number of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in blood samples between T0 (before start of cARV) and T1 (after 6 months of cARV)

recovery of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in peripheral blood after 6 months of cARV)

Inclusion Criteria: naïve for antiretroviral treatment met the criteria to start cART according to International Guidelines written informed consent signed Exclusion Criteria: treatment with glucocorticosteroids and any immune modulating medication for more than seven days in the previous month any past or current systemic malignancy, history of inflammatory diseases of the small or large intestine pregnancy anemia, use of anticoagulants, and any contraindications to phlebotomy or colonoscopy.

d'Ettorre G, Baroncelli S, Micci L, Ceccarelli G, Andreotti M, Sharma P, Fanello G, Fiocca F, Cavallari EN, Giustini N, Mallano A, Galluzzo CM, Vella S, Mastroianni CM, Silvestri G, Paiardini M, Vullo V. Reconstitution of intestinal CD4 and Th17 T cells in antiretroviral therapy suppressed HIV-infected subjects: implication for residual immune activation from the results of a clinical trial. PLoS One. 2014 Oct 23;9(10):e109791. doi: 10.1371/journal.pone.0109791. eCollection 2014.