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

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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)

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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

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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

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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

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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

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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

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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

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Onset of IRIS

Source: AIDS 2005, Vol 19 No4 ;399-406, Samuel A. Shelburne et al

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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

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Hostsusceptibility

CD4< 50

Microbial antigens

Risk factors for IRIS

Adapted from French et al, 2004

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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.

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Management

• Temporary cessation of ART has to be considered if potentially life threatening forms of IRIS develop