Risk factors for Discontinuation of
HIV Post-Exposure Prophylaxis
Italian Registry of Antiretroviral Post-Exposure Prophylaxis (IRAPEP)
www.inmi.it [email protected]
Istituto Nazionale per le Malattie Infettive
“Lazzaro Spallanzani”, Roma
Grant ISS 40H32-RC IRCCS
Objective
 Describe the use of PEP recommended to prevent
HIV infection after a significant exposure, whether
occupational or sexual, as recorded within the
Italian Registry of Antiretroviral Post-Exposure
Prophylaxis – (IRAPEP) in the period 1996-2012
(104 participating centres).
Acknowledgements
Spedali Civili di BRESCIA
Osp. Sacco MILANO
Policlinico “A. Gemelli” ROMA
Osp. Cotugno NAPOLI
Osp. Amedeo di Savoia TORINO
AUSL 3 Spedali Riuniti PISTOIA
Osp. degli Infermi RIMINI
A.O. S. Croce CUNEO
Ospedale Niguarda MILANO
Policlinico Monteluce PERUGIA
Ospedale Maggiore BOLOGNA
AO Ospedali Riuniti TRIESTE
Osp. Gen. Prov. MACERATA
Azienda Ospedaliera Di PARMA
Azienda ULSS N° 9 TREVISO
Osp. Galliera GENOVA
AO Umberto I ANCONA
Osp. SS . Giacomo e Cristoforo MASSA
Arcispedale S. Maria Nuova R. EMILIA
Osp. S. Martino GENOVA
Osp. Civile SS. Antonio e Biagio ALESSANDRIA
Policlinico Di MODENA
Osp. S. Anna COMO
AO Careggi FIRENZE
Azienda Policlinico Universitario UDINE
Ospedale Per Gli Infermi FAENZA
PO M. Bufalini CESENA
CRAIDS Prov. UDINE
Osp. Civile RAVENNA
Osp. S. Paolo SAVONA (18)
PO Misericordia GROSSETO
Osp. SIENA
Ospedale Civile LECCO
Ospedale Gen. Reg. Valle D’Aosta AOSTA
Policlinico “S. Orsola- Malpighi” BOLOGNA
Osp. Belcolle VITERBO
Osp. Civico e Benfratelli PALERMO
Umberto I MESTRE
Ospedali Riuniti - USL 2 SANREMO (12)
Ospedale Campo Di Marte LUCCA
Osp. S. Eugenio ROMA
Ospedale Carlo Poma MANTOVA
Ospedale S. Andrea VERCELLI
Osp. Gen. Provinciale RIETI
Ausl PIACENZA
P.O. S. Andrea POZZO di GOTTO
Centro MST GORIZIA
P.O.Ospedale Uboldo-Az. Osp. MELEGNANO
Policlinico S. Matteo PAVIA
Ospedale Infantile Regina Margherita TORINO
Ospedale Umberto I FROSINONE
Ospedale S. Gerardo MONZA
Istituti Ospitalieri CREMONA
Ospedale Generale Regionale BOLZANO
A.O. Bianchi Malacrino Morelli R. CALABRIA
Osp. S. Maria Sopra I Ponti AREZZO
Ospedali Riuniti SALERNO
A.O. Maggiore Della Carita‘ NOVARA
Arcispedale S.Anna FERRARA
Osp. Pediatrico Casa Del Sole PALERMO
Osp.S.Salvatore PESARO
Osp. Papardo MESSINA
Ospedale San Martino BELLUNO
Ospedale "A. Di Summa“ BRINDISI
Presidio Ospedaliero di PESCARA
Ist. Clinici Di Perfezionamento MILANO
Ospedale Civile Spirito Santo PESCARA
Az. Osp. "Ospedale Maggiore" CREMA
Ospedale S. Maria Goretti LATINA
PO Morgagni FORLI’
Ospedali Riuniti BERGAMO
Azienda Ospedaliera "S. Maria“ TERNI
Az.Ospedaliera Vito Fazzi LECCE
AUSL 15 Presidio Osp. CITTADELLA
Az. ULSS 18 ROVIGO
Osp. Ferrazzano Asl6 LAMEZIA TERME
Policlinico BARI
Ospedale FORMIA
A.O S. Antonio Abate TRAPANI
Ospedale Civile S. Bortolo VICENZA
Ospedale Civile San Salvatore AQUILA
Ospedale Umberto I SIRACUSA
Osp. Civile BUSTO ARSIZIO
Presidio Osp. U.L.S.S. N. 2 FELTRE
Policlinico MESSINA
A.O. Pugliese Ciaccio CATANZARO
Ospedale"Guadagna“ PALERMO
Ospedale Umberto I ENNA
Ospedale S.M. Maddalena TRIESTE
Ospedale S.Antonio Abate ERICE
Ospedale S. Giovanni di Dio FONDI
Ospedale Civile RAGUSA
Ospedale ISILI
Ospedale Di PALMANOVA
Ospedale Civile PADOVA
Ospedale Civile ASTI
Osp. Ss. Filippo E Nicola AVEZZANO
Azienda USL di IMOLA
Osp. Civile Vittorio Emanuele III GELA
Ospedale Maggiore LODI
Distribution of Cases Starting HIV Post-Exposure Prophylaxis by
Type of Exposure and Year (absolute number)
(5582 cases, IRAPEP 1996-2012)
600
500
400
300
200
100
0
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Not Occ- not Sex exp
Sexual exp
Occ not HCW
HCWs
Distribution of Cases Starting HIV Post-Exposure Prophylaxis by
Type of Exposure and Year (absolute number)
(5582 cases, IRAPEP 1996-2012)
400
350
300
250
200
150
100
50
0
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
HCWs
Occ not HCW
Sexual exp
Not Occ- not Sex exp
Trend of Cases Starting HIV Prophylaxis after Sexual Exposure
(IRAPEP 1997-2012)
200
180
160
140
120
100
80
60
40
20
0
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Objectives
 Describe the use of PEP recommended to prevent
HIV infection after a significant exposure, whether
occupational or sexual, as recorded within the
Italian Registry of Antiretroviral Post-Exposure
Prophylaxis – (IRAPEP) in the period 1996-2012
(104 participating centres).
 Determine the main factors associated with
discontinuation (D) of PEP and discontinuation for
side effects (DSE).
Cases Enrolled in the Italian Registry of Antiretroviral PostExposure Prophylaxis (IRAPEP), 1996-2012
Subjects Starting
5582
HIV-neg source
1318 (23.6%)
HIV-pos at baseline
16 (0.3%)
Subjects Treated
4248 (76.1%)
IRAPEP, 1996-2012
Total
Gender
Age (years)
Category
Source HIV serostatus
Viremia (HIV-pos source)
Female
Male
Unknown
Median (IQR)
Range
HCWs
Occ not HCW
Sexual exp
Not Occ-not Sex exp
Unknown
Positive
Detectable
Undetectable
Unknown
4248
2012
2142
94
1877
403
1465
503
1809
2439
743
581
1115
%
47.4
50.4
2.2
35 (28-43)
3-82
44.2
9.5
34.5
11.8
42.6
57.4
30.5
23.8
45.7
Viremia
HCWs (%)
<2009
2009+
Total
Occ not HCW
(%)
Sexual exp Not Occ-not Sex
(%)
exp (%)
Total (%)
Undetectable
180 (16.1)
9 (9.5)
169 (32.7)
34 (16.9)
392 (20.3)
Detectable
365 (32.7)
20 (21.1)
159 (30.8)
53 (26.4)
597 (30.9)
Unknown
571 (51.2)
66 (69.5)
189 (36.6)
114 (56.7)
940 (48.7)
Undetectable
66 (41.0)
0 (-)
114 (36.9)
9 (32.1)
189 (37.1)
Detectable
48 (29.8)
1 (8.3)
92 (29.8)
5 (17.9)
146 (28.6)
Unknown
47 (29.2)
11 (91.7)
103 (33.3)
14 (50.0)
175 (34.3)
Undetectable
246 (19.3)
9 (8.4)
283 (34.3)
43 (18.8)
581 (23.8)
Detectable
413 (32.3)
21 (19.6)
251 (30.4)
58 (25.3)
743 (30.5)
Unknown
618 (48.4)
77 (72.0)
292 (35.4)
128 (55.9)
1115 (45.7)
IRAPEP, 1996-2012
Total
Gender
Age (years)
Category
Source HIV serostatus
Viremia (HIV-pos source)
PPE regimen
Changed initial regimen
Side effects
PEP completed
Female
Male
Unknown
Median (IQR)
Range
HCWs
Occ not HCW
Sexual exp
Not Occ-not Sex exp
Unknown
Positive
Detectable
Undetectable
Unknown
2 NRTI+PI
Other
No
Yes
No
Yes
No
Yes
4248
2012
2142
94
1877
403
1465
503
1809
2439
743
581
1115
3458
790
3980
268
2184
2064
1335
2913
%
47.4
50.4
2.2
35 (28-43)
3-82
44.2
9.5
34.5
11.8
42.6
57.4
30.5
23.8
45.7
81.4
18.6
93.7
6.3
51.4
48.6
31.4
68.6
Regimens of Prophylaxis by Side Effects and PEP discontinuation
Side
effects (%)
PEP
discontinued (%)
Discontinuation
for side effects (%)
Total
AZT+3TC
231 (42.3)
181 (33.2)
86 (15.8)
546
AZT+3TC+IDV
551 (54.4)
355 (35.1)
203 (20.1)
1012
AZT+3TC+NFV
238 (54.2)
135 (30.8)
58 (13.2)
439
AZT+3TC+LPV
661 (53.0)
374 (30.0)
125 (10.0)
1247
TDF+FTC+LPV
170 (32.8)
176 (34.0)
44 (8.6)
518
Other
195 (42.9)
105 (23.1)
40 (8.8)
455
MegaPEP *
18 (58.1)
9 (29.0)
4 (12.9)
31
2064 (48.6)
1335 (31.4)
560 (13.2)
4248
I° Regimen
Total
*>3 drug classes:NRTI+PI
+NNRTI 45.2%
+Entry & Fusion Inhibitor 25.8%
+Integrase Inhibitor 19.3%
PEP Discontinuation by selected characteristics
Total
Gender
Age
HIV source
Side effects
Type of exposure
Regimen
N
MLR-OR (95% CI)#
%
Total
4248
1335
31.4
M
2142
639
29.8
1
F
2012
671
33.3
1.3 (1.1-1.4)
Unknown
94
25
26.6
0.8 (0.5-1.3)
40+ years
1258
363
28.9
1
30-39 years
1346
412
30.6
1.1 (1.0-1.4)
<30 years
1053
591
378
35.9
1.4 (1.2-1.7)
182
30.8
2439
621
25.5
1.0 (0.8-1.2)
1
Unknown
1809
714
39.5
1.9 (1.6-2.2)
No
2184
637
29.2
1
Yes
2064
698
33.8
1.3 (1.2-1.5)
HCWs
1877
592
31.5
1
Occ not HCW
403
167
41.4
1.2 (1.0-1.6)
Sexual exp
1465
402
27.4
0.7 (0.6-0.9)
Not occ-not sex
AZT+3TC
503
174
34.6
1.0 (0.8-1.3)
546
181
33.2
1
AZT+3TC+IDV
1012
355
35.1
1.2 (0.9-1.5)
AZT+3TC+LPV
1247
374
30.0
1.0 (0.8-1.2)
AZT+3TC+NFV
439
135
30.8
1.0 (0.7-1.3)
TDF+FTC+LPV
518
176
34.0
1.2 (0.9-1.5)
Other
486
114
23.5
0.8 (0.6-1.1)
Unknown
Positive
MLR-OR:
Multivariate
Logistic
Regression
Odds Ratio
# Final model
obtained
after
backwardelimination
p<0.05
Association of PEP “Discontinuation for side effects” according to Selected Characteristics
Total
Discontinued for side
effects
N
Gender
Age
HIV source
Type of exposure
Regimen
MLR-OR (95% CI)#
%
Total
M
4248
560
2142
F
221
13.2
10.3
1
2012
324
16.1
1.5 (1.2-1.8)
Unknown
94
15
16.0
0.9 (0.5-1.7)
40+ years
1258
163
13.0
1
30-39 years
1346
156
11.6
1.0 (0.8-1.3)
<30 years
1053
591
11.2
20.8
1.0 (0.8-1.3)
Unknown
118
123
1.4 (1.0-1.8)
Positive
2439
301
12.3
1
Unknown
1809
259
14.3
1.3 (1.0-1.5)
HCWs
1877
323
17.2
1
Occ not HCW
403
74
18.4
1.2 (0.9-1.6)
Sexual
1465
101
6.9
Not occ-not sex
AZT+3TC
503
62
12.3
0.5 (0.4-0.6)
0.7 (0.5-1.0)
546
86
15.8
1
AZT+3TC+IDV
1012
203
20.1
1.5 (1.1-1.9)
AZT+3TC+LPV
1247
125
10.0
1.0 (0.7-1.2)
AZT+3TC+NFV
439
58
13.2
1.0 (0.7-1.5)
TDF+FTC+LPV
518
44
8.5
0.7 (0.5-1.1)
Other
486
44
9.1
0.7 (0.5-1.0)
MLR-OR:
Multivariate
Logistic
Regression
Odds Ratio
# Final model
obtained
after
backwardelimination
p<0.05
Follow-up (>3months)
(IRAPEP 1996-2012)
Follow-up
Total
Completed
Not completed
2087 (49.1)
2161 (50.9)
4248
completed
1669 (57.3)
1244 (42.7)
2913
discontinued
418 (31.3)
917 (68.7)
1335
side effects
267 (47.7)
293 (52.3)
560
other reasons
151 (19.5)
624 (80.5)
775
Total
PEP
Discontinued for
Seroconversions
Main available characteristics of the n°? serocoverted patients
MSM, receptive anal intercourse with occasional
HIV+ partner (broken condom). HIV and HCVneg at baseline.
MSM, receptive anal intercourse with stable
HIV+ partner (broken condom).
AZT+3TC+IDV after
30h for 4 wks.
Adherence 100%
AZT+3TC+LPV after
13h for 19 days.
Adherence 80%
HCV Ab+ after 3 months
HIV Ab+ after 7 months
HIV Ab+ after 4 months.
Molecular match with partner’s strain. Previous
unprotected exposures.
MSM, receptive anal intercourse with stable
HIV+ partner (broken condom).
Previous PEP 2 yrs before.
AZT+3TC+LPV after
4h for 4 wks. 2°PEP
Adherence 100%
HIV Ab+ after 3 months. Molecular match with
partner’s strain.
Subsequent exposures.
MSM, receptive anal intercourse with stable
HIV+ partner (broken condom).
AZT+3TC+LPV after
22h for 4 wks.
Adherence 100%
HIV Ab neg at 3 months, HIV+ at 6 months.
Subsequent exposure to a different partner
(found HIV+).
MSM, 2 pep for receptive anal intercourse with
stable HIV+ partner (broken condom).
Previous PEP 1 yr before.
AZT+3TC+LPV after
2h for 4 wks. 2°PEP.
Adherence 100%
HIV Ab+ WB indeterminate (seroconversion) after
5 months. Subsequent exposures.
MSM, 2 PEP for receptive anal intercourse with
occasional HIV+ partner (no condom).
Previous PEP 8 months before.
TDF+FTC+LPV after
27h for 6 days. 2°PEP.
Adherence 100%
HIV Ab+ after 7 months (on the date of the
beginning of second PEP); referred positive at 3
months. Subsequent exposures ??
M-Het, insertive vaginal and anal intercourse
with occasional HIV unkwnon serostatus partner
(no condom).
AZT+3TC+LPV after
31h for 4 wks.
Adherence?%
HIV Ab+ after 14 months.
No follow up test after PPE.
Subsequent exposures.
M-Het, insertive vaginal intercourse with
occasional HIV+ partner (no condom).
TDF+FTC+LPV
after 4 h for 4 wks.
Adherence 100%
HIV Ab/RNA neg after 2 months
HIV Ab+ after 3 months.
Subsequent exposures?
MSM che assumono PEP sono a maggior rischio di
infezione?
AIDS 2009, 23:1119–26
AIDS 2012, 26:505–12
AIDS 2012, 26:1581–83
Conclusions
• PEP Discontinuation seems to be influenced by
sex, risk perception (type of exposure and source
serostatus) and tolerability of prescribed regimen.
• PEP discontinuation does not seem related to drug
regimen
• Newer regimens are better tolerated, but other
factors play a more significant role in
discontinuation of PEP and follow-up.
• Discontinuation associated to loss to follow up
- Individuals taking PEP should receive an
enhanced risk reduction and adherence
counseling, and an active follow-up [AII].
Referents
Puro V, De Carli G, Piselli P, Schifano E, Cimaglia C, Agresta A, Pittalis
S, Ippolito G, Signorini L, Niero F, Fantoni M, Franco A, Salassa B,
Vivarelli A, Morigi G, Micheloni G, Vitullo D, Degli Antoni AM, Colangeli
V, Moretti MV, Crosato I, Castelli P, Cassola G, Mantia E, Drenaggi D,
Laganà S, Giobba M, Massari M, Magnani G, Albertini F, Dodi F, Gubian
F, Longoni E, Gori A, Rosa I, Ambu S, Brighi S,Toscano L, Nencioni C,
Calcagno G, Maillard M, Folsi MF, Traverso A, Ballardini G, Trifiletti F,
Caterini A, Saitta M, De Gennaro M, Lorusso A, Ferrea G, Moise G,
Costa P, Marchili M, Paolillo F, Cristina G, Gabiano C, Minoli L, Tacconi
D, Placido G, Anzalone E, Rizzi M, Lichtner M , Sighinolfi L, Carnevale
G, Cioffi G, Placido G, Govoni A, Portelli V, Argentero PA