Tubercolosi, HIV e migrazione: una reale emergenza?
SESSIONE II -ˇ HIV e Tubercolosi nella persona immigrata
Miriam Lichtner
Dipartimento di Malattie Infettive e Sanità Pubblica
Sapienza Università di Roma Polo Pontino
Componente dell’ Italian National Focal Point –
Infectious Diseases and Migrant”
Sergej
• 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
IRIS:
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)
6
Antiretroviral Therapy Improves Qualitative
and Quantitative Immune Defects
Immune suppression/deficiency
HIV
replication
Immune
activation
Qualitative/functio
nal immune defects
Quantitative
immune defects
Response to recall
antigens
CD4 counts
Impaired
pathogen
-specific
immunity
OI
Immune Reconstitution
HAART
HIV
replication
Immune
activation
Migueles, Buenos Aires 2003
Qualitative/function
al immune defects
Quantitative immune
defects
Reversal of anergy
Redistribution, death (HIV-,
activation-induced),
production (peripheral
expansion and thymic)
Lymphocyte
proliferative capacity
Improved
pathogenspecific
immunity
Improved
immune
control
7
Immune reconstitution inflammatory
syndrome
Patients Started on ART
2330
Immune reconstitution syndrome
302
85
HERPES ZOSTER
81
TUBERCULOSIS
72
CMV RETINITIS
31
PCP
28
CRYPTOCOCCOSIS
HANSEN'S
3
OTHERS
3
Source: GHTM, Chennai
8
Defining IRIS
Required criterion
Supportive criterion
Worsening symptoms of
inflammation/infection
Increase in cd4 cell count of > 25
cells/cu.mm
Temporal relationship with starting Biopsy demonstrating well formed
antiretroviral treatment
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
9
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:10Journal of Antimicrobial Chemotherapy (2006) 57, 167-170;
Samuel A. Shelburne, Martin Montes and Richard J.Hamill
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
11
Source: Battegay and Drechsler; Current Opinion in HIV and AIDS; 2006, 1; 56-61
Defining IRIS: Minor Criteria
• Increase in CD4 cell count
• Increase in measured specific immune
response
• Spontaneous resolution of symptoms
without specific therapy
Source: Battegay and12
Drechsler; Current Opinion in HIV and AIDS; 2006, 1; 56-61
Onset of IRIS
13
Source: AIDS 2005, Vol 19 No4 ;399-406, Samuel A. Shelburne et al
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
14
Risk factors for IRIS
Microbial
antigens
Host
susceptibility
CD4< 50
Adapted from French et al, 2004
15
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.
16
Management
• Temporary cessation of ART has to be
considered if potentially life threatening
forms of IRIS develop
17