Persistence of HIV in Gut-Associated Lymphoid Tissue despite Long-Term Antiretroviral Therapy

Human immunodeficiency virus (HIV) persists in peripheral blood mononuclear cells despite sustained, undetectableplasmaviremiaresultingfromlong-termantiretroviraltherapy.However,thesourceofpersistentHIVin such infected individuals remains unclear. Given recent data suggesting high levels of viral replication and profounddepletionofCD4Tcellsingut-associatedlymphoidtissue(GALT)ofanimalsinfectedwithsimianimmunodeficiencyvirusandHIV-infectedhumans,wesoughttodeterminethelevelofCD4Tcelldepletionaswellas the degree and extent of HIV persistence in the GALT of infected individuals who had been receiving effective antiviral therapy for prolonged periods of time. We demonstrate incomplete recoveries of CD4 T cells in the GALTofaviremic,HIV-infectedindividualswhohadreceivedupto9.9yearsofeffectiveantiretroviraltherapy.In addition,wedemonstratehigherfrequenciesofHIVinfectioninGALT,comparedwithPBMCs,intheseaviremic individualsandprovideevidenceforcross-infectionbetweenthese2cellularcompartments.Together,thesedata provideapossiblemechanismforthemaintenanceofviralreservoirsrevolvingaroundtheGALTofHIV-infected individualsdespitelong-termviralsuppressionandsuggestthattheGALTmayplayamajorroleinthepersistence of HIV in such individuals.