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

28 Abstracts WePeA5808-WeOrB1264

XIV International AIDS Conference

forms in high amounts (>3-5 fold increase, 18-30 ng/ml) with respect to unstimulated control.
Conclusions: Our findings support the hypothesis that the LD780 isoform of MIPla is the most potent natural HIV-1 inhibitory chemokine and, furthermore, indicate potential interference modalities through which HTLV-2 may curtail HIV-1
infection and delay disease progression in co-infected patients.
Presenting author: Claudio Casoli, Institute of Medical Pathology, University of
Parma, via Gramsci, 14, 1-43100 Parma, Italy, Tel.: [phone], Fax: [phone], E-mail: claudio.casoli @ unipr.it
WePeA5808 IDifferent effects of Nef-mediated HLA-classl
down-regulation on HIV-1-specific CD8+ T cell
cytolytic activity and cytokine production
H. Tomiyama'1, H. Akari2, A. Adachi3, M. Takiguchi'1. '1Center for AIDS Research
Kumamoto Univ, Division of Viral Immunology Kumamoto, Japan; 2NIAID, NIH,
Bethesda, United States; 3The Univ of Tokushima School of Med., Tokushima,
Japan
Back ground: A previous study suggested that Nef-mediated HLA-classl downregulation affects the cytolytic activity of HIV-1-specific CTL clones for HIV-1 infected primary CD4+T cells. However it is still unclear whether HIV-1 specific
CTLs can produce soluble antiviral factors by stimulation with nef+ HIV-1 infected
CD4+ T cells.
Methods: We investigated the effect of Nef-mediated HLA-classl down regulation on HIV-1 specific CTL activity, cytokine production, and ability to suppress
HIV-1 replication using primary CD4+T cells infected with a wild type HIV-1 strain
(NL-432), or a HIV-1 strain that express a single amino acid mutant Nef protein
that fails to induce HLA-classl down-regulation but retains other Nef function (NLM20A).
Results: HIV-1 specific CTL clones were not able to kill primary CD4+T cells
infected with Nef-positive HIV-1 (NL-432) but efficiently lysed CD4+T cells infected with NL-M20A. However these CTL clones stimulated with NL-432 infected
CD4+T cells were able to produce cytokines, albeit at a lower level than when
stimulated with CD4+ T cells infected with NL-M20A. Replication of NL-432 was
partially suppressed in a co-culture of HIV-1 infected CD4+T cells and HIV-1 specific CTL clones, while replication of NL-M20A was completely suppressed.
Conclusion: These results indicate that Nef- mediated downregulation of HLAclassl molecules greatly affected for cytotoxic activity of CTLs to infected cells
whereas that was not much affective for cytokine production by CTL. These results suggested that HIV-1 specific CD8+ T cells may partially suppress the replication of nef+ HIV-1 by production of soluble antiviral factors such as chemokine
and interferon-y. Furthermore these findings may explain the mechanism why
HIV-1 specific CD8+ T cells partially but not completely control HIV-1 replication
in vivo.
Presenting author: Hiroko Tomiyama, Division of Viral Immunology, Center for
AIDS Research Kumamoto Univ., 2-2-1 Honjo Kumamoto, 860-0811, Japan, Tel.:
[phone], Fax: [phone], E-mail: [email protected].
ac.jp
WeOrB1262 1Switching protease inhibitors to Nevirapine (NEV),
Efavirenz (EFA) or Abacavir (ABA): A randomized,
multicenter, open-label, simplification trial
E. Martinez', D. Podzamczer2, E. Ribera3, P. Domingo4, H. Knobel5,
D. Dalmau6, M. Riera7, J.M. Gatell'. 'Hospital Clinic, Servei Farmacologia,
Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain; 2Hospital de Bellvitge,
L'Hospitalet, Spain; 3Hospital Vail dHebron, Barcelona, Spain; 4Hospital de Sant
Pau, Barcelona, Spain; 5Hospital del Mar, Barcelona, Spain; 6Mutua de
Terrassa, Terrassa, Spain; 7Hospital Son Dureta, Palma de Mallorca, Spain
Background: Responding patients on a protease inhibitor (PI)-containing highly
active antiretroviral regimen (HAART) may have their therapy simplified by switching from PI to either NEV, EFA, or ABA. So far, head-to-head comparisons between these three drugs have not been reported.
Methods: Adult patients on at least one PI plus two nucleoside analogue reverse
transcriptase inhibitors (NRTI) with plasma HIV-1 RNA <200 copies/mL for 36
months were randomly assigned to switch from the PI component to either NEV,
EFA, or ABA. The primary end-point was the proportion of patients remaining
<200 copies/mL affer 12 months of follow-up.
Results: A total of 460 patients were evaluable (NEV: 155, EFA: 156, ABA: 149).
Baseline characteristics did not differ among groups. At 12 months, patients remaining below 200 copies/mL were 94% (NEV), 94% (EFA), and 87% (ABA) in
the on-treatment analysis (p=0.06), and 78% (NEV), 74% (EFA), and 77% (ABA)
in the intent-to-treat (ITT) analysis (p=0.7). Mean changes in CD4 cells per cubic
millimeter were +41 (NEV), +51 (EFA), and +51 (ABA) (p=0.44). A significantly
(p=0.009) lower proportion of patients discontinued the study medication due to
adverse events in ABA (6%) than in NEV (16%) and EFA (17%) arms. 23 of 28

patients (82%) who developed a virological failure had received prior suboptimal
therapy with one or two NRTI alone. Genotypic analysis revealed mutations to the
study medication and to at least one of the NRTIs contained in the failing regimen
in all cases. The % of patients with cholesterolemia above 240 mg/dL at the end
of the study was significantly lower in the ABA arm (9%) as compared with the
NEV (24%) or EFA (22%) arms (P=0.01).
Conclusions: The efficacy of switching from PI to either NEV, EFA, or ABA in

responding patients on stable HAART was almost identical in the ITT analysis.
Less adverse effects leading to discontinuation but a higher risk of virological
failure were found with ABA as compared with NEV or EFA.
Presenting author: Juan A. Arnaiz, Servei Farmacologia, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain, Tel.: [phone], Fax: [phone],
E-mail: [email protected]
WeOrB1263 Switch of saquinavir 400 mg/ritonavir 400 mg to
saquinavir 1000 mg/ritonavir 100 mg during BID
four drug antiretroviral therapy in patients with
viral load less than 200 copies/ml
W.A. O'Brien', D. Rojo', E. Acosta2, F. Felizarta3, D. Pearce4, D.T. Jayaweera5,
F. Visnegarwala6. ' University of Texas Medical Branch, Route 0435, 301
University Blvd, Galveston, TX, United States; 2University of Alabama at
Birmingham, Birmingham, AL, United States; 3Community Health Center,
Bakersfield, CA, United States; 4St. Luke Medical Group, San Diego, CA, United
States; 5university of Miami School of Medicine, Miami, FL, United States;
6 Baylor University School of Medicine, Houston, TX, United States
Background: Ritonavir (RTV) enhances saquinavir (SQV) exposure via inhibition of SQV hepatic metabolism. Durable viral load (VL) suppression has been
demonstrated with SQV 400 mg/RTV 400 mg BID, but this regimen can be associated with hyperlipidemia as well as frequent adverse events, perhaps associated with the RTV dose used. PK and clinical outcome data support the use
of RTV 100 mg BID to enhance SQV 1000 mg BID. We assessed the efficacy,
plasma SQV/RTV, fasting plasma lipid levels, and tolerability after dose modification of combination SQV/RTV from 400/400 to 1000/100 in patients with VL
suppression.
Methods: Subjects (VL <200 copies/ml) who had been receiving RTV 400
mg/SQV 400 mg for at least 6 months without prior use of >1 other PI for
more than 3 months, were randomized to continue current therapy or to switch
SQV/RTV to 1000 mg/100 mg BID. Other ARV were not changed. Plasma SQV
and RTV levels were measured at baseline, 1 and 6 months, and fasting plasma
lipids were measured every 3 months.
Results: 23 patients participated. No patients in the study had increases in
VL >400 copies/ml through month 6. One month post-randomization peak and
trough drug levels were obtained at 2.8 ~ 0.4h and 12.4 ~ 1.5h post dose, respectively. Values are shown for the two treatment groups in the table. Three
patients dropped out, one with pancreatitis, and one patient with a strong family
history of cardiovascular disease had sudden death (age 46).
400 mg/400 mg Peak (ng/ml) Median (ng/ml) Trough (ng/ml) 535
SQV (n=11) 1482 ~ 1118 1092 545 + 413 535
RTV (n=11) 5989 ~ 4302 5024 3464 ~ 1985 3416
1000 mg/100 mg
SQV (n=9) 1822 ~ 2263 702 1077 ~ 2002 RTV (n=9)
RTV (n=9) 1022 + 1031 692 1271 ~ 1483 374
In 1000/100 patients, between baseline and 6 mos, fasting triglyceride levels fell
from 635 to 375 mg/dl (P=0.038), and cholesterol levels fell from 323 to 236 mg/dl
(p>0.05). Improved tolerability was documented.
Conclusion: Modification of SQV-400/RTV-400 to SQV-1000/RTV-100 is safe
and effective. There are significant reductions in triglycerides over six months,
trends toward reduction in cholesterol levels, and improved tolerability, likely related to the reduction in ritonavir drug levels.
Presenting author: William A. O'Brien, Route 0435, 301 University Blvd, Galveston, TX, United States, Tel.: [phone], Fax: [phone], E-mail:
wobrien @utmb.edu
WeOrB1264 GENOPHAR: an open prospective study of
plasmatic drug measurements (PDM) associated
with genotypic resistance testing (GRT) in patients
failing antiretroviral therapy
P. Bossi', G. Peytavin2, C. Delaugerre3, D.J. David4, N. Ktorza',
M. Bonmarchand5, H. Ait Mohand', C. Lamotte2, R. Cacace', A. Simon5,
V. Calvez3, F Bricaire', D. Costagliola4, C. Katlama'. 'Dept. of Infectious
Diseases, Pitie Salpetriere Hospital, Paris, France; 2Dpt of Pharmacology, Bichat
Hospital, Paris, France; 3Dpt of Virology Pitie Salpetriere Hospital, Paris,
France; " INSERM SC4, Paris, France; 5 Dpt of Internal Medicine, Pitie
Salpetriere Hospital, Paris, France
Background: To evaluate the benefit of PDM in association with GRT to optimize
therapy in pts failing antiretroviral treatments (ART).
Methods: In a single center, Pts with HIV-1 RNA>1000 cp/ml and stable ART
in the last 3 mths were randomized in 2 groups: genotypic group (G) and geno
pharmacologic group (GP). Pts were evaluated monthly clinically, for safety parameters, for HIV-1 RNA, for CD4 cell counts and for PI and/or NNRTI peak and
trough plasma levels until W 24. ART was selected by an expert committee according to GRT (G and GP) and PDM (GP) at W 4. Treatment could be modified
at each visit according to toxicity, poor virological response and PDM. At W 12,
results of PDM were available for G. Primary end-point study was the % of pts
with HIV-1 RNA<200 cp/ml at W 12.