Program Supplement [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

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[LBPEB90211
NEKA study: NRTI-sparing regimen
Negredo, Eugenia,, Bonjoch, Anna', Sirera, Guillem', Puig,
Jordi', Videla, Sebastia', Kurowski, Michel2, Bonafont,
Xavier', Ruiz, Lidia', Clotet, Bonaventura' (Spain; 2Germany)
Background: NRTIs have been recently linked to mitochondrial
toxicity (MT). Nevirapine (NVP) has been associated with a
favourable lipid profile while lopinavir/ritonavir (LPV/rtv)
increases cholesterol and triglyceride levels. Objectives: To
study the efficacy of LPV/rtv 400oo/loo100mg + NVP 200oomg, BID,
and the pharmacokinetic (PK) interactions between both
drugs. To assess if NVP counteracts the LPV/rtv effect on lipid
metabolism and if this strategy reverses MT.
Methods: A total of 30 ARV-experienced but LPV/rtv-naive
patients (pt) with VL 9 months (mo) were included in this pilot
study and randomised to LPV/rtv + NVP (Arm A, n=16) or to
LPV/rtv + 2 NRTIs (the previous NRTIs) (Arm B, n=14). HIV RNA,
CD4+, fasting lipid metabolism, hepatic profile and LPV through
levels (Cmin, in lo pt) were performed every 3mo and mitochodrial
(m) DNA/ nuclear (n) DNA ratio every 6mo.
Results: At 6mo, both arms mantained viral suppression although
CD4 rose significantly only in group A (from 552 to 758 cel/mm3 in
group A and from 640 to 668 cel/mm3 in B). Neither significant
changes in mean GPT and GGT nor in triglyceride levels were seen
in any group, while an increase in mean cholesterol was observed
in both groups (from 205 to 250 mg/dl in group A and from 179 to
226 mg/dl in B). Only one pt from group A was lost to follow-up.
Mean LPV Cmin levels were similar between both arms at steady
state conditions: 4924 ng/ml in group A (range: 2130-6940 ng/ml)
vs 4432 ng/ml in group B (range: 335o-612o ng/ml); only one
patient of each group showed LPV Cmin levels <3500 ng/ml.
mDNA/nDNA ratios are currently being analysed.
Conclusions: At 6mo the switch to an NRTIs-sparing regimen
consisting on LPV/rtv (3 pills) + NVP (1 pill) BID, seems to be
safe and, at least, equally potent than LPV/rtv + 2NRTIs.
However, NVP was not able to counteract the lipid
abnormalities related to LPV/rtv. This study was partially
supported by Abbott and Boehringer Ingelheim Lab.
Corresponding author: Negredo, Eugenia, Lluita contra la SIDA
foundation. Germans Trias i Pujol Hospital. C/ Canyet S/N,
Badalona 08916, Barcelona, Spain,
Email: [email protected]
LBPEB90221
Preliminary results of a randomized, controlled trial of
pegylated interferon alpha 2-b with ribavirin vs interferon alpha
2-b with ribavirin for treatment of chronic HCV in HIV-i patients
Mallolas, Josep, Laguno, Montse, Murillas, Javier, SdnchezTapias, Josd M-, Bianchi, Luis, Miquel, Rosa, Garcfa-Gasalla,
Mercedes, Blanco, Josd Luis, Martfnez, Esteban, Milinkovic,
Ana, Le6n, Agata, Loncd, Montse, Gatell, Josep M9 (Spain)
Background: Although HCV is a major morbidity in HIV infected
patients, current therapies has low success and high intolerance.
We evaluate the efficacy and safety of interferon (IFN) + ribavirin
(RBV) vs PEG-INF + RBV in co-infected patients.
Methods: This is a randomized, single center, open label trial.
Inclusion criteria for this trial: detectable HCV RNA, ALAT higher
than 1.5 fold upper normal limit, abnormal liver histology, CD4 >
250/mm3 and HIV-1 RNA< lo.ooo copies/mL on stable
antiretroviral therapy. Patients were randomized to INF alpha 2-b 3
MIU tiw or PEG-IFN alpha 2-b 150 mcg qwk if body weight > 75 Kg
or ioo mcg qwk if <75 Kg. Each arm received RBV 8oo mg per day

if < 6o Kg, looo mg if 60-75 Kg and 1200oo mg if > 75 kg. Primary
endpoint was HCV RNA undetectable at week 24. Virologic
responders (VR) continued therapy until week 48 if they had HCV
genotype i or 4 and/or HCV RNA at baseline > 8oo00.ooo UI/mL.
Results: Until April 2002, 117 eligible patients were randomized
and 62 of them already started therapy. Age, gender, HCV- RNA,
HCV genotype, undetectable HIV-RNA, CD4, fibrosis and
necroinflamatory activity score at entry were not significantly
different between arms. PEG had significantly higher VR
(p=o.o36) among the 43 and 23 patients who reached week 12
and 24 respectively. Almost all patients in both groups
developed side effects related to the therapy mainly grade 1 or
2. Total CD4 fell in both arms (- 165 in PEG vs- 161 in INF arm)
at week 12 and the median HIV-1 RNA viral load was
undetectable at baseline and did not change at week 12.
Conclusions: For patients co-infected with HCV and HIV, PEG
IFN alpha 2b + RBV is associated with superior VR compared
with INF alpha 2b + RBV. Although side effects were very
frequent, the majority of them were mild or moderate. Total
CD4 fell in both arms but no evidence of deleterious effect on
HIV-1 control were seen. Long-term efficacy and safety will be
addressed with trial completion.
Corresponding author: Mallolas, Josep, ICIll. Infectious
Dioseases Service, Hospital Clinic, Villarroel 170, Barcelona,
Spain, Tel: [phone], Fax: [phone],
Email: [email protected]
[LBPEB9023
Pharmacokinetic (pk) interaction between lopinavir/ritonavir
(LPV/r) and amprenavir (APV) does not affect virologic
response to the combination of LPV/r, APV and RTV in
HIV-infected patients (pts) with multiple treatment failure
(Puzzle 1-ANRS1o4 Study)
Raquin, Gilles Taburet, Anne-Marie, Chene,
Genevieve, Morand-Joubert, Laurence, Droz, Cecile, Vincent,
Isabelle, Clavel, Francois, Girard, Pierre-Marie (France)
Background: A combination of APV, LPV and RTV could prove
effective in pts failing multiple antiretrovirals (ARV) provided
that pk interactions between APV and LPV have no negative
effect on virologic response.
Methods: A prospective, randomized, open-label, multicentre
trial in pts with CD4+<500oo/mm3 and plasma HIV RNA
(pVL)lo.ooo copies/mi after at least 2 PIs and 1 NNRTI. For the
first 2 wks, pts were randomized to receive either: LPV/r (gri),
APV (1200mg/d) + RTV (200mg/d) (gr2), LPV/r + RTV
(20omg/d) (gr3), APV (120omg/d) + RTV (4o00mg/d) (gr4). From
wks 2 to 26, all pts received APV and LPV/r with an additional
boost of 2oomg/d of RTV for gr 3 and 4.
Results: 40 pts were randomized, 37 started treatment. At
baseline, median CD4+ was 207/mm3, median pVL 4.7 loglo
copies/ml, median nb of PI mutations: 7. Average nb of ARV
taken prior to randomization was 7.7. Median APV and LPV
plasma trough conc. were:
APV Cmin APV Cmin LPV Cmin LPV Cmin

Grp;
RTV bid gr2 (n=6)
RTVioo
W2 1514
(680-3067)
W6 873
(569-1816)

gr4; (n=8)
RTV200
2334
(648-5317)
721
(323-1104)

gri; (n=13) gr3; (n=lo)
RTVioo RTV200
7126 10488
(3342-14052) (6414-13784)
4604 10439
(1578-9041) (4530-12615)

XIV International AIDS Conference BARCELONA - JULY 7-12

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