Diapositive 1

1
Tolerability of Post-Exposure Prophylaxis (PEP)
of HIV Infection with the Combination of
Tenofovir/Emtricitabine and Lopinavir/Ritonavir
Tablet Formulation (Truvada Kaletra)
Capetown, July, 22, 2009
W Tosini, Ph Muller, Th Prazuck, G
Benabdelmoumen, E Peyrouse, B Christian, Y
Quertainmont, E Bouvet, Ch Rabaud. Groupe dEtude
sur le Risque dexposition des Soignants aux
Agents Infectieux (GERES), COREVIH Lorraine
Champagne Ardenne, Centre Hospitalier Régional,
Orléans, Hôpital Bichat Claude-Bernard, Hôpital
Sainte Marguerite, Marseille, Hôpital Bicêtre,
Paris, France
2
BACKGROUND

• French guidelines concerning PEP
• four-week course of triple ARV therapy with
  two
• NRTIs and one PI/r.
• PEP efficacy improvement
• adherence and dropout rate must be considered
• Studies previously performed
• PEP regimen interruption remained significant

3
RATIONAL OF THE CHOICE OF THIS NEW PEP REGIMEN
(1)

• TDF/FTC
• Efficacy of TDF when used as PEP in monkeys
• Better tolerability of tenofovir than zidovudine
  when used as PEP

4
RATIONAL OF THE CHOICE OF THIS NEW PEP REGIMEN
(2)

• LPV/r tablets
• reduced pill burden (from 6 to 4 daily)
• less variability of LPV blood concentrations
• no requirement of food restriction
• potentially reduced gastrointestinal side effects.

5
METHOD (1)
Multicentric observational prospective study
Duration 18 months (start at November 1st 2006)
Planned inclusions 200 people
6
METHOD (2) STUDY DESIGNpotential exposure to
HIV within the previous 48 h, age gt 18 years,
and ability to give informed consent
Risk evaluation
PEP prescription
No PEP prescription
Source patient known to be HIV infected AIDS
specialist immediately consulted
No consent Standard Treatment
Study Inclusion
7
METHOD (3) TOLERABILITY ASSESSMENT

• On day 14 and day 28 (the end of treatment),
  adherence and toxicity were evaluated
• Adverse effects were recorded on case report
  forms
• To minimize this bias, all participants in this
  study were contacted by telephone on day 14 and
  day 28 of PEP for adverse effects, and 3 months
  after exposure for HIV serostatus

8
CHARACTERISTICS AT BASELINE (1)
66,4
33,9
SEX RATIO
N 2 4 9
MEAN AGE
31,5 10 years
EXPOSURE
5 (2)
40 (16)
204 (82)
77.5
74.5
80
SEX
36 y
31 y
30 y
MEAN AGE
Median duration of time between exposure and
first drug intake
2 H
15 H
9
CHARACTERISTICS AT BASELINE (2)
HIV serostatus of source patients
Occupational exposures
Non occupational exposures
Known in 70
Known in 24
83 cases (33.3)
POSITIVE
NEGATIVE
60 (72)
23 (28)
10
R E S U L T S (1)
249
27
LOST TO FOLLOW-UP (11)
27
7
22
166
11
R E S U L T S (2)
249
27
PEP discontinued shortly after treatment
initiation because the source patient was
subsequently tested HIV-seronegative or because
the injury was reassessed as low-risk by a
specialized physician
27
7
Median PEP duration 3 days
22

• AE 11 cases (40)
• DIARRHEA 80
• ASTHENIA 66
• ABDOMINAL PAIN 44

166
12
R E S U L T S (3)
249
27
PEP discontinued for reasons other than adverse
effects (i.e. patient decision) (2.5)
27
7
22
166
13
R E S U L T S (4)
249
27
discontinued before Day 28 due to adverse events
(9)
27
Median PEP duration 7 days
7
2 skin rashes TDF/FTC 1 renal lithiasis LPV/r
1 rhabdomyolysis
22
166
14
R E S U L T S (5)
249
27
Persons completing the 28 days of TDF/FTCLPV/r
tablet formulation PEP 66.5
27
96 (58)
11 (7)
7
59 (35)
good
22
moderate
bad
166
15
ADVERSE EVENTS
59
78
78
NAUSEA / VOMITING
DIARRHEA
ASTHENIA
16
BIOLOGICAL ABNORMALITIES
35 HYPERTRIGLYCERIDEMIA with including only
4.4 grade 2 abnormalities
15.7 HYPERCHOLESTEROLEMIA grade 1 only
GRADE 3 ALT INCREASE in 3 cases
GRADE 3 HYPOPHOSPHATEMIA in 3 cases
grade 4 CPK abnormalities (rhabdomyolysis case)
leading to stop PEP
17
HISTORICAL COMPARISON

• To compare tolerability of different PEP regimens
  successively evaluated in similar study
  condition
• zidovudine/lamivudine nelfinavir combination
  bid (AZT/3TC NFV) 1998-2001
• zidovudine/lamivudine lopinavir/ ritonavir SGC
• bid (AZT/3TC LPV/r-SGC) 2002-2003
• lamivudine tenofovir atazanavir boosted by
  ritonavir once a day (3TC TDF ATV/r)
  2004-2005
• tenofovir/emtricitabine once a day lopinavir/
  ritonavir tablet formulation bid (TDF/FTCLPV/r)
  2006-2008

18
COMPARISON BETWEEN DIFFERENT PEP REGIMEN (1)
p lt0 .0001
p 0.001
p 0.03
19
COMPARISON BETWEEN DIFFERENT PEP REGIMEN (2)
p lt 0.0001
p 0.18
p 0.49
20
CONCLUSION

• When compared with historical controls who have
  received one of the 3 PI-based PEP regimens
  previously tested in the same study conditions,
  the rate of treatment interruption was
  significantly lower with TDF/FTCLPV/r tablet
  formulation PEP regimen.
• This PEP regimen offers 2 others advantages
• Co-formulation of TDF/FTC, as well as of LPV and
  the ritonavir booster, permit reduced number of
  pills
• No special storage conditions required for
  LPV/r-containing PEP regimen, which makes easier
  PEP kit preparation and storage in clinics

21
ACKNOWLEDGEMENTS
Dr W. Tosini GERES French Study Group concerning
blood occupational exposure Pr E Bouvet