905 
Post-exposure Prophylaxis of HIV Infection: Comparison of Tolerability of 4 PEP Regimens
Christian Rabaud*1, C Burty1, C Valle1, B Christian1, C Penalba1, T Prazuck2, P Chavanet3, J Faucher4, J Faucher, and T May1
1CISIH Nancy Lorraine Champagne Ardenne, France; 2CHR d'Orleans, France; 3Univ Hosp Dijon, France; and 4Univ Hosp Besancon, France
Background: Post-exposure prophylaxis (PEP) can
be offered to persons recently exposed to the risk of HIV infection. In France, 2 nucleoside
reverse transcriptase inhibitors (NRTI) + 1 protease inhibitor (PI) are
recommended as PEP. PEP must be efficient and well tolerated, but, today, few
data are available on the tolerability of such PEP. In the same study
conditions, we have successively evaluated tolerability of 4 PEP regimens: zidovudine/lamivudine
+ nelfinavir (AZT/3TC + NFV) combination
twice daily; AZT/3TC ++lopinavir/ritonavir (LPV/r) twice
daily; AZT/3TC + tenofovir (TDF) twice daily; 3TC + TDF
+ atazanavir (ATV) boosted by ritonavir
once a day.
Method: Multicentric prospective study performed in 9 hospitals in France. Studies were performed in 1999-2001 (AZT/3TC + NFV), 2002 (AZT/3TC + LPV/r), 2003 (AZT/3TC
+ TDF), and 2004 (3TC + TDF + ATV/r).
Results: Excluding patients lost of follow-up
immediately after inclusion (25%, 18%, 14%, and 17%, respectively in, studies
AZT/3TC + NFV, AZT/3TC + LPV/r, AZT/3TC + TDF, and 3TC + TDF + ATV/r),
301 patients were enrolled in AZT/3TC + NFV study, 139 in AZT/3TC + LPV/r, 148 in AZT/3TC + TDF, and 126 in 3TC + TDF + ATV/r. In
49%, 21%, 19.5%, and 16.5% of cases, respectively, PEP was quickly discontinued
because the source patient was subsequently tested HIV or because
the injury was reassessed as “low-risk”; respectively, 4%, 3%, 2%, and 3% of
these cases, side effects were noted before this discontinuation. Results
concerning tolerance in other cases were reported in table. Finally, the rate of stop due to adverse events occurrence
and the rate of side effect occurrence appeared significantly higher in the AZT/3TC
+ NFV PEP study than in the AZT/3TC + LPV/r, AZT/3TC + TDF, or 3TC + TDF + ATV/r studies (stop: p =
0.04, p = 0.004, p = 0.02, respectively; side effects: p <0.001,
p <0.001, and p <0.001, respectively). No significant differences were
observed concerning rate of stop and rate of side effects occurrence between AZT/3TC
+ LPV/r, AZT/3TC + TDF, and 3TC
+ TDF + ATV/r studies. In these studies, no HIV seroconversion was recorded.
|
PEP
regimen
|
PEP
discontinued
for adverse events before Day 28
|
Patients
completed 28 days of PEP
|
|
reporting
side effects
|
without
side effects
|
|
AZT/3TC + NFV
|
53 (34.5%)
|
69 (45%)
|
32 (20.5%)
|
|
AZT/3TC + LPV/r
|
25 (22.5%)
|
40 (36.5%)
|
45 (41%)
|
|
AZT/3TC + TDF
|
22 (18.5%)
|
44 (37%)
|
53 (44.5%)
|
|
3TC + TDF + ATV/r
|
22 (21%)
|
36 (34%)
|
47 (45%)
|
Conclusions: In light
of our data, and considering that previous studies in health care workers have shown
that 65 to 95% of subjects receiving AZT + 3TC + IDV experienced adverse
effects, and considering further that AZT/3TC + TDF
could be less
effective against HIV than combinations including a PI and that 3TC
+ TDF + ATV/r is more expensive than AZT/3TC + LPV/r, we today recommend AZT/3TC
+ LPV/r as PEP.
|
