Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

XIV International AIDS Conference

Abstracts WeOrB1265-WeOrB1303 29

Results: 137 pts were included at DO (G, n=69 pts/GP, n=68 pts) and 127 were
followed up to W 12. At baseline median values were: HIV-1 RNA (Log cp/ml:
G=4.1; GP=4.0); CD4 cell count (/mm3; G=292; GP=294) and number of prior
drugs (G=7; GP=8). Median number of resistance mutations was 8 in G (NRTI=3;
NNRTI=1; PI=4) and 10 in GP (NRTI=4; NNRTI=2; PI=6). At W 8, ART was adjusted according to the PDM in 10/67 GP pts (15%). By ITT missing equal failure
analysis at W 12, an HIV-1 RNA<200 cp/ml was achieved in 30/69 pts (43%)
in the G group versus 28/68 pts (41%) in the GP group (ns). At W 24, HIV-1
RNA<200 cp/ml was achieved in 34/59 pts (58%) in the G group versus 40/61
pts (66%) in the GP group; median drop in HIV-1 RNA level was -1.3 log cp/ml
[-3.1 to 1.4] and -1.6 log cp/ml [-2.9 to 0.7] respectively (ns). At W 24, median
increase of CD4 cell count was 59/mm3 (G) and 60/mm3 (GP)(ns).
Conclusions: This study shows that combining GRT with the use of an expert
committee to monitor individual subsequent therapy in pts with multiple resistance
mutations was associated to a high antiviral efficacy with 62% of pts<200 cp/ml.
The benefit of using PDM over 2 mths was not evidenced in this study.
Presenting author: Philippe Bossi, Dpt of Infectious Diseases, Pitie-Salpetriere
Hospital, 47/83 bd de LHopital, 75013 Paris, France, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
WeOrB1265 Safety and efficacy evaluation of a phase IV
randomised, open-label, multicentre trial of
indinavirlritonavir (800/100 mg bid) vs.
saquinavir/ritonavir (1000/100 mg bid) in adult
HIV-1 infection: The MaxCminl trial
P. Cahn', U.B. Dragsted2, C. Pedersen3, B. Peters4, A. Duran5, N. Obel6,
J.M. Gatell7, C. Leen8, J.V. Lunzen9, A. Stoehr10, J. Lederman1,
J.D. Lundgren2. 1 Fundacidn HUESPED, CHIP, Dept. of Infectious Diseases 144,
Hvidovre University Hospital, DK - 2650 Hvidovre, Argentina; 2 Hvidovre
University Hospital Copenhagen, Denmark; 3Odense University Hospital
Odense, Denmark; 4St. Thomas Hospital, London, United Kingdom; 5Hospital
JM Ramos Mejia, Buenos Aires, Argentina; 6 Skejby Hospital, Aarhus, Denmark;
7Hospital Clfnic de Barcelona, Barcelona, Spain; 8 Western General Hospital,
Edinburgh, United Kingdom; 9 University Hospital Eppendorf, Eppendorf,
Germany; 'AK St. Georg, Hamburg, Germany; Sound Shore Medical Center,
New Rochelle, United States
Background: This trial is the first head-to-head comparison of ritonavir(r)boosted PI treatments (tx). The objectives of the trial were to compare 2Rvirological outcome between the study arms including the proportion of patients with
HIV-RNA < 400 c/ml at 48 weeks, to compare the proportion of patients experiencing (serious) adverse events ((S)AEs), and that discontinued the randomised
tx prematurely.
Methods: Open-label, randomised (1:1), multi-centre, phase IV trial evaluating
the safety and efficacy of indinavir/r (IDV/r) vs. saquinavir (SAQ/r) in HIV-1 infected patients (age > 18) at 48 weeks of tx. Concomitant use of > 2 NRTI/NNRTI
was decided prior to randomisation by the treating physician.
Results: The randomised tx was initiated in 306 of 317 randomised patients. No
differences were observed at baseline between the study arms in demographic,
clinical or laboratory variables nor in the use of any antiretroviral drug prior to inclusion or at baseline. Through December 2001 (equal to 90% of follow-up), 98
(32%) patients had discontinued the randomised tx - 56/158 (35%) in the IND/r
arm vs. 42/148 (28%) in the SAQ/r arm - primarily due to G-I toxicity: 16 (10%)
vs. 13 (9%), respectively. Only 7 (2%) were lost to follow-up. HIV-1 RNA was <
400 c/ml in 87% of patients (123/141) at Week 48. A total of 133 AEs grade 3 or
4 were reported in 50 (32%) patients in the IND/r arm vs. 29 (20%) in the SAQ/r
arm (see table), of which 7 vs. 4 patients had abnormal liver function test. Further,
68 SAEs were reported in 28 (18%) patients in the IND/r arm vs. 21 (14%) in the
SAQ/r arm. Complete Week 48 data will be available in May 2002.
Adverse Event IDV/r SAQ/r Total
Cardio-pulm. 7 0 18
Renal 10 0 10
Other G-I 18 16 34
Nervous system 7 4 11
Skin 3 2 5
Fever & fatigue 3 3 6
Laboratory 15 16 31 *
Other 20 8 28
* LFT (11) hyperlipidemia (7) haematology (6) hyperglycedemia (3)
Serious Adverse Event IDV/r SAQ/r Total
(hosp. adm., life threat., fatal) (n = 36) (n = 32) (n = 68)
Cardio-pulm. 6 7 13
Renal 5 0 5
Other G-I 8 9 17
Nervous system 6 6 12

Skin 1 1 2
Fever & fatigue 3 2 5
Laboratory 1 2 3
Other 6 5 11
Conclusion: The two regimens result in virological control in most patients and
are reasonably well tolerated. More patients in the IND/r than in the SAQ/r arm

experienced (S)AEs. The final analysis of Week 48 toxicity and efficacy data -
stratified for randomisation - will be presented.
Presenting author: Ulrik Bak Dragsted, CHIP, Dept. of Infectious Diseases 144,
Hvidovre University Hospital, DK - 2650 Hvidovre, Denmark, Tel.: [phone]
15, Fax: [phone], E-mail: [email protected]
WeOrB1266 Tenofovir DF: A 48-week final analysis from a
phase Ill randomized, double blind, placebo
controlled study in antiretroviral treatment
experienced patients (study 907)
A.L. Pozniak', A. Plettenberg2, W. Rozenbaum3, A. Sonnerborg4, J.M. Molina5,
J. Gatell6, S.S. Chen7, B.P. Kearney7, M.D. Miller7, D.F Coakley7, A. Cheng7.
'Chelsea and Westminster Hospital, United Kingdom; 21FI Institut, Hamburg,
Germany; 3'Rothschild Hospital, Paris, France; 4Huddinge University Hospital,
Huddinge, Sweden; 5Saint-Louis Hospital, Paris, France; 6Hospital Clinic,
Barcelona, Spain; 7Gilead Sciences, Foster City, CA, United States
Background: Tenofovir DF (TDF) is a single tablet, once daily nucleotide reverse
transcriptase inhibitor with potent activity against wild-type and nucleoside resistant HIV.
Methods: Multi-center, international, double blind, randomized study of 550 treatment experienced patients with HIV RNA between 400 and 10,000 copies/mL,
who received TDF 300 mg or placebo for 24 weeks in addition to stable (> 8
wks) background antiretroviral therapy (ART). Single dose (day 1) and long term
pharmacokinetics (PK) were assessed in a subset of patients. After week 24, all
patients received open label TDF 300 mg through 48 weeks.
Results: Mean baseline HIV and demographic characteristics: HIV RNA 4457
copies/mL; CD4 cell count 427 cells/mm3; prior ART use 5.4 years; male (85%);
Caucasian (69%) and approximately 41 years old. 253 patients were randomly
assigned to a virology substudy; baseline resistance mutations were 94% NRTI,
58% PI, and 48% NNRTI. Tenofovir PK were unchanged over 12, 24, 36 or 48
weeks of dosing compared to Day 1 (mean AUC = 2.8 ig hr/mL) (p > 0.37) and
no evidenceof drug related renal toxicity was observed. Through 48 weeks, 3%
(n=8) of patients developed the tenofovir-associated K65R resistance mutation.
Placebo Tenofovir DF Tenofovir DF
24 Weeks 24 Weeks 48 Weeks
n = 182 n = 368 n =368
DAVG HIV RNA (log10 copies/mL -0.03 -0.61 -0.57
HIV RNA < 400(%) 13 45 41
HIV RNA _< 50(%) 1 22 18
DAVG CD4 Count (cells/mm3) -11 +13 +13
Study Drug Discontinuation (%) 6 6 12
> Grade 3 Adverse Events (%) 14 14 20
> Grade 3 Laboratory Abnormalities (%) 38 25 35
Conclusions: Through 48 weeks, once daily tenofovir DF 300 mg provides
durable antiviral suppression in treatment experienced patients with an unchanged PK and a safety profile which remains similar to placebo.
Presenting author: andrew cheng, 333 lakeside drive, foster city, california,
94404-1147, United States, Tel.: [phone], Fax: [phone], Email: andrew.cheng @gilead.com
WeOrB1303 Frequency, type, severity, and duration of adverse
drug events on highly-active antiretroviral therapy
(HAART) in a resource-poor setting
H. Reuter, T Kasper, C. Poole, V. Skefile, E. Goemaere. Medecins Sans
Frontieres, PO Box 27401, Rhine Road, Sea Point, 8055, South Africa
Background: In May 2001, Medecins Sans Frontieres began an antiretroviral
therapy project in three government-run primary health care centers in Khayelitsha, a poor township of Cape Town, South Africa. Concerns that the population
served (primarily poor, sick [median CD4 cell count at baseline of 48] African
women, many with anemia and elevated liver functions at baseline) would suffer
serious toxicity have been raised by scientists and by politicians, and have been
used as a justification for withholding treatment.
Methods: To date 85 patients have begun HAART, with 15 new enrolling per
month (100% African, 67% women). Adverse events were reported to doctors at
regular medical consultations and in support groups for people on HAART.
Results: At medical consultations, 45% of patients (38 of 85) reported at least
one adverse event (mean number reported: 1.4), while 58% (38 of 65 attending
support groups) reported at least one in the support groups (mean 2.9). Laboratory screening detected abnormalities in 48% (41/85; mean 1.6). Most common
adverse events reported at clinics were nausea (21% of patients), rash (19%),
and headache (12%), while in support groups the most frequently mentioned
were rash (27%), headache (24%), and nausea (15%). Most common lab ab
normalities were neutropenia (29% of patients) and elevated liver function tests
(28%). Of the adverse events reported at clinics, 87% were Grade 1, 13% Gr 2.
Of the lab abnormalities, 54% were Gr 1, 21% Gr 2,17% Gr 3, 8% Gr 4. 8 patients
changed therapy for intolerance. 58% of adverse events reported at consultations
were mentioned at only one visit; duration of those persisting for multiple visits
was a median of one subsequent visit.
Conclusion: Two approaches to reporting adverse events show comparable re