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Tubercolosi , HIV e migrazione: una reale emergenza ?. SESSIONE II -ˇ HIV e Tubercolosi nella persona immigrata. La gestione della persona immigrata con coinfezione parte II. Miriam Lichtner Dipartimento di Malattie Infettive e Sanità Pubblica Sapienza Università di Roma Polo Pontino - PowerPoint PPT Presentation
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LA GESTIONE DELLA PERSONA IMMIGRATA CON COINFEZIONE
PARTE II
Miriam LichtnerDipartimento di Malattie Infettive e Sanità Pubblica
Sapienza Università di Roma Polo PontinoComponente dell’ Italian National Focal Point – Infectious
Diseases and Migrant”
Tubercolosi, HIV e migrazione: una reale emergenza?
SESSIONE II -ˇ HIV e Tubercolosi nella persona immigrata
• Dopo 4 mesi di ART e 2 di anti-TB (11/04/07): febbre elevata con
sospetto di IRIS, inizia deltacortene e streptomicina
• CD4+ 98/mmc, HIV-RNA<50
• Dimissione 26/4/07 controllo DH dopo 1 sett
Sergej
IRIS: IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME
6
Quadri storici di IRIS• Reazione paradossale nella TB dopo inizio
trattamento• Reazione infiammatoria nei pz con lebbra in
trattamento • Recupero del sist. immune dopo trapianto di
midollo e chemioterapia• Risposta atipica infiammatoria ai micobatteri
atipici nei pz in terapia con AZT (anni 80)
7
Antiretroviral Therapy Improves Qualitative and Quantitative Immune Defects
Immune suppression/deficiency
HIV replication
Immune activation
Qualitative/functional immune
defectsResponse to recall
antigens
Quantitative immune defects
CD4 counts
Impaired pathogen-specific immunity
OI
HAART
HIV replication
Immune activation
Qualitative/functional immune
defectsReversal of anergy
Lymphocyte proliferative capacity
Quantitative immune defects
Redistribution, death (HIV-, activation-induced),
production (peripheral expansion and thymic)
Improved pathogen-specific
immunity
Immune Reconstitution
Improved immune control
Migueles, Buenos Aires 2003
8
Immune reconstitution inflammatory syndrome
28
31
72
81
85
3
3
OTHERS
HANSEN'S
CRYPTOCOCCOSIS
PCP
CMV RETINITIS
TUBERCULOSIS
HERPES ZOSTER
Patients Started on ART 2330
Immune reconstitution syndrome 302
Source: GHTM, Chennai
9
Defining IRIS
Required criterion Supportive criterionWorsening symptoms of inflammation/infection
Increase in cd4 cell count of > 25 cells/cu.mm
Temporal relationship with starting antiretroviral treatment
Biopsy demonstrating well formed granulomatous inflammation or unusually exuberant inflammatory response
Symptoms not explained by newly acquired infection or disease or the usual course of a previously acquired disease
> 1 log10 decrease in plasma viral load
Source: CID J 2006;(1 June) 42: 1639-46
10
Defining IRIS• Proposed criteria for the diagnosis of IRIS• HIV positive• Receiving HAART
– Decrease in HIV-1 RNA level from baseline– Increase in CD4 cells from baseline(may lag HIV-1 RNA
decrease)• Clinical symptoms consistent with inflammatory
process• Clinical course NOT consistent with:
– Expected course of previously diagnosed OI– Expected course of newly diagnosed OI– Drug toxicity
Source: Journal of Antimicrobial Chemotherapy (2006) 57, 167-170; Samuel A. Shelburne, Martin Montes and Richard J.Hamill
11
Defining IRIS: Major Criteria • Previous diagnosis of AIDS• Concurrent Antiretroviral Therapy; Increase in CD4 count
and Decrease in plasma vireamia by > 1 log copies/ml• Atypical presentation of ‘opportunistic infection or tumor’
i.e.– localized disease or – exaggerated inflammation or – atypical inflammatory response or– worsening of pre existing disease. – Symptoms consistent with infectious/inflammatory condition
• Symptoms not explained by normal course of previous or new OI or side effect of ART
Source: Battegay and Drechsler; Current Opinion in HIV and AIDS; 2006, 1; 56-61
12
Defining IRIS: Minor Criteria • Increase in CD4 cell count• Increase in measured specific immune
response• Spontaneous resolution of symptoms
without specific therapy
Source: Battegay and Drechsler; Current Opinion in HIV and AIDS; 2006, 1; 56-61
13
Onset of IRIS
Source: AIDS 2005, Vol 19 No4 ;399-406, Samuel A. Shelburne et al
14
Risk factors
• Risk factors at base line:– Lower CD4 count prior to start of ART– Higher HIV-1 RNA levels at base line– Initiating ART in close proximity to starting
therapy for an OI• Response to therapy & the development of
IRIS:– Rapid fall in HIV-1 RNA level during the first 3
months of therapy Source: Journal of Antimicrobial Chemotherapy (2006) 57, 167-170;Samuel A. Shelburne, Martin Montes and Richard J.Hamill
15
Hostsusceptibility
CD4< 50
Microbial antigens
Risk factors for IRIS
Adapted from French et al, 2004
16
Management• Mild form (with ongoing ART)
– Observation • Localized IRIS (with ongoing ART)
– Local therapy such as minor surgical procedures for lymph node abscesses
• Most of the situations (with ongoing ART)– Unmasking &/or Recognition of ongoing infections >>
Antimicrobial therapy to reduce the antigen load of the triggering pathogen;
– Reconstituting immune reaction to non-replicating antigens >> no antimicrobial therapy. Short term therapy with corticosteroids or non-steroidal anti inflammatory drugs to reduce the inflammation.
17
Management
• Temporary cessation of ART has to be considered if potentially life threatening forms of IRIS develop
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