Since the beginning of the AIDS epidemics, a relevantnumber of scientists of different disciplines have beeninvestigating the interactions between HIV and its host fromthe immunological and virological perspective. It was understoodthat the first moments of the infection are crucial indetermining the entire course of the disease. Indeed, thevirus is immediately able to provoke a variety of damagesand alterations in several compartments, including not onlythe peripheral blood and lymph nodes, but also the mucosalimmune system. Several studies performed in patients experiencingacute, primary infection had shown the importanceof a massive immune activation as a key mechanism that,through the induction of apoptosis, could lead to the depletionof CD4þ T cells that is typical of HIV infection.More recent data demonstrate that acute HIV infectionis accompanied by a marked and selective loss of memoryCD4þ T cells, predominantly from the mucosal surfaces.Indeed, in the simian model of acute infection, 30–60% ofthese cells throughout the body are infected by the virus,and most of these infected cells disappear within 4 days.Highly active antiretroviral therapy (HAART) has significantlychanged the course of HIV infection either by prolongingboth survival or and the time free from opportunisticinfections. However, everyday life of HIVþ patients hasbeen modified by the administration of complex therapeuticregimens. It is common opinion that when started, antiretroviraltherapy for HIV has to be continued life-long, butlong-term treatment with multiple drugs often leads to theonset of serious side effects and unacceptable toxicity, and,in most patients, to treatment fatigue. In the attempt toavoid either the onset of side effects or a poor adherenceto therapy, and to maintain an efficient HIV-specific immuneresponse, several groups have started clinical studies evaluatingdifferent strategies of therapy interruptions. Sincemany years, our group has been conducting several studiesto investigate the main features of the CD4 cell-guided interruptions.This strategy allows the patient to remain off-therapyfor periods that are extremely much longer than thoseof the structured therapy interruptions, and also representsan ideal model to study not only the immediate reaction ofthe immune system to the reactivation of the virus, but alsothe evolution of the immune response with time. We haverecently investigated the changes of several immunologicalmarkers during CD4 cell monitored therapy interruption ina group of 17 patients. Viral load and activation of CD8þlymphocytes increased significantly in the first two monthsafter treatment discontinuation, then decreased and remainedstable. CD4þ cell count decreased in the first4 months, then remained stable; naı¨ve, central memory,effector memory, and terminally differentiated CD4þ cellschanged proportionally in a similar manner. Patients whohad to restart therapy within 1 year always presented more CD4þ naı¨ve cells and less CD4þ effector memory lymphocytes,while the others had a higher expression of CD127on peripheral T cells. Data will be presented on the importanceof immune activation and of the interleukin-7 systemin these situations.
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|Anno di pubblicazione:||2007|
|Titolo:||The interaction between HIV and its host|
|Autori interni:||COSSARIZZA, Andrea|
|Rivista:||CYTOMETRY. PART B, CLINICAL CYTOMETRY|
|Appare nelle tipologie:||Articolo su rivista|
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