Programme Supplement [International Conference on AIDS (16th: 2006: Toronto, Canada)]

Late Breaker Abstracts

Results: Phylogenetic analysis identified major viral subtypes
in this east African population: Clade Al at -60%, and clade D
at ~20%/o with a small amount (9%) of clade C. Quasi analysis of
1200 clade Al gag sequences identified multiple positive selected
sites in 5 major gag proteins. We observed different outcomes
by correlating the positive selected sites with patient HLA and
CD4 counts. For example, positive selected amino acid 31 in p24
significantly correlates to HLA-B*5703 (p = 1.96e-10) and was.::.::........ also associated with a higher mean CD4 counts (p = 0.038). It is
consistent with previous studies that B57 is associated with slower
peiu disease progression. Conversely, positive selected residue 42 in p17
is significantly associated with HLA-Cw4 (p = 0.002) and lower mean
CD4 count (p = 0.012), implying less favourable disease outcome.
Negative correlations (HLA and CD4) were also observed, indicating
possible viral adaptation with associated fitness cost.
Conclusions: This study helps to explain why certain HLA
alleles are associated with different disease outcomes and is an
efficient approach to identify and classify escape mutations in
HIV-1 gag. This information can be used in peptide based vaccine
development.
THLBO308
Genomic signal analysis of HIV-1 clade F protease and
reverse transcriptase variability
P.D. Cristea, R. Tuduce. University POLITEHNICA of Bucharest,
Biomedical Engineering Center, Bucharest, Romania
Late Breaker Background: The protease and most of the reverse transcriptase
Abstracts genes of HIV-1 Clade F isolates from 28 Romanian patients have
been sequenced at the National Institute of Infectious Diseases,
Bucharest, Romania.: The conversion of genomic symbolic
sequences into digital signals allows the use of powerful signal
processing methods for the analysis of nucleotide sequences.
SMethods: Phase analysis of genomic signals corresponding to
the nucleotide sequences has been used to identify changes that
induce multiple resistance to antiretroviral treatment and to track
patterns of PR and RT variability. A new method for describing
sets of related signals by a common reference and individual
differences has been developed for this purpose.
Results: An interesting result is that variations in the genes tend
to compensate each other. A genomic sequence satisfies more
structural restrictions than a,,plain text", and resembles more
to a,,poem", which obeys rules of symmetry giving its,,rhythm"
and,,rhyme". The recurrence of patterned structures in nucleotide
sequences results in mathematical rules satisfied by genomic
signals. The paper also presents a method for estimating changes
in RNA secondary structure. For PR inhibitors, it has been found
that, whereas changes in response to antiretroviral therapy in
treatment naive patients occur at the level of the final enzyme
product, primarily preventing the blocking of the PR catalytic site
under the effect of the drug, in multiple drug resistant patients,
significant changes also occur at the level of gene RNA secondary
structure. The changes consists in the replacement of large loops
and bulges by smaller closed-loop structures.
Conclusions: The new results reveal a more complex mechanism
of both drug action and drug-resistance development process.
P. D. Cristea, "Representation and Analysis of DNA sequences", in
Genomic Signal Processing and Statistics, Editors E.G. Dougherty,
I. Shmulevici, J. Chen, Z. J. Wang ---- Hidawi, 2005, pp.15-65.
Track B
THLBO201
A two-year randomized controlled clinical trial in
antiretroviral-naive subjects using lopinavir/ritonavir (LPV/
r) monotherapy after initial induction treatment compared
to an efavirenz (EFV) 3-drug regimen (Study M03-613)
W. Cameron1, B. da Silva', J. Arribas', R. Myers4, N. Bellos',

N. Gilmore', K. Niemi2, K. Wikstrom2, M. King2, G. Hanna2, S.

Brun 2. 'University of Ottawa at the Ottawa Hospital, Ottawa,
Canada, 'Abbott Laboratories, Abbott Park, United States, 'Hospital
La Paz, Madrid, Spain, 4Body Positive Inc., Phoenix, United States,
sSouthwest Infectious Disease Associates, Dallas, United States,
6McGill University Health Center, Montreal, Canada
Background: With robust pharmacokinetics, high potency and
high genetic barrier to resistance, LPV/r is a good candidate for
evaluation as monotherapy for HIV infection.
Methods: 155 antiretroviral-naive HIV-1+ subjects were
randomized 2:1 to LPV/r + zidovudine (ZDV) + lamivudine (3TC)
induction (n=104) for at least 24 weeks followed by maintenance
LPV/r monotherapy after 3 consecutive monthly viral loads (VL)
<50 copies/mL, or to EFV+ZDV+3TC (n=51). The primary endpoint
was the proportion achieving and maintaining VL <50 copies/mL
through 96 weeks.
Results: Baseline characteristics were similar between arms.
92 (88%) of 104 LPV/r subjects started monotherapy. 79 LPV/r
(69/92 on monotherapy) and 34 EFV-treated subjects completed
the study. Drug-related discontinuations occurred in 3% of
LPV/r-treated and 2% of EFV-treated subjects. In the primary
analysis, 50% of LPV/r-treated and 61% of EFV treated subjects
achieved and maintained VL <50 copies/mL through 96 weeks
(intent-to-treat, previous failure=failure, p=0.23). By KaplanMeier analysis, the proportions maintaining VL <50, and <500
copies/mL through 72 weeks on LPV/r after deintensification
were 62% and 84% respectively. Corresponding KaplanMeier estimates for EFV subjects after 3 consecutive VL <50
copies/mL were 91% <50 (p=0.002 vs. LPV/r monotherapy) and
95% <500 copies/mL (p=0.10 vs. LPV/r monotherapy). LPV/r
monotherapy subjects with VL rebound to 50-500 copies/mL
generally demonstrated viral resuppression to <50 copies/mL
while continuing LPV/r monotherapy (11/12) or with resumption
of NRTIs (2/4). New PI resistance mutations were detected
in 2/15 (13%) LPV/r-treated subjects, while NNRTI resistance
mutations were detected in 1/5 (20%) EFV-treated subjects
(p>0.9).
Conclusions: After successful induction treatment with LPV/
r+ZDV+3TC, LPV/r monotherapy continuously maintained VL
suppression in a majority of subjects. LPV/r monotherapy had
more intermittent VL increases between 50 and 500 copies/mL
versus EFV+ZDV+3TC, but most subjects returned to <50 copies/
mL. LPV/r monotherapy may be effective in selected patients.
THLBO202
MONARK Trial (MONotherapy AntiRetroviral Kaletra): 48 -Week analysis of lopinavir/ritonavir (LPV/r) monotherapy
compared to LPV/r + zidovudine/lamivudine (AZT/3TC) in
antiretroviral-naive patients
J.-F. Delfraissy', P. Flandre2, C. Delaugerre3, A. Horban4, P.-M. Girard', C.
Rouzioux6, M. Norton', I. Cohen-Codar', P. NgoVan', J.-P. Chauvin'. 'Le
Kremlin Bicetre Hospital, Department of Internal Medecine, Univ 11, Paris,
France, 2Pierre and Marie Curie Univ, Inserm Unit 720, Paris, France, 3Necker
Virology EA 3620, Univ 5, Paris, France, 4AIDS Diagnosis and Therapy Center,
Hospital of Infectious Diseases, Warsaw, Poland, sSaint-Antoine Hospital,
Infectious Diseases, Paris, France, 'Necker Virology EA 3620, Univ Paris,
France, 'Abbott Park, Chicago, United States, 'Abbott France, Rungis, France,
'Abbott GPRD, Rungis, France
Background: Guidelines for the use of antiretrovirals for HIV-1
infection recommend combining 3 agents. However, toxicities,
cost, complexity of such regimens warrant the search for other
options.
Methods: MONARK is a pilot, prospective, open-label,
randomized, 96-week trial comparing the safety and efficacy
of LPV/r monotherapy to a standard LPV/r+AZT/3TC regimen.
Antiretroviral naive subjects without baseline resistance to study
drugs, viral load (VL) 100,000 copies/mL, CD4 100 cells/mm3,
were randomized to either LPV/r or LPV/r+AZT/3TC. The primary
endpoint was VL <400 copies/mL at W24 and <50 copies/mL at
W48. Sub-optimal virologic response was defined as (i) <1 log VL

decrease by W4 (ii) VL >400 c/mL by W24 (iii) VL rebound after
VL<400 c/mL, confirmed in a second specimen.

XVI INTERNATIONAL AIDS CONFERENCE * 13-18 AUGUST 2006 * TORONTO CANADA * PROGRAMME SUPPLEMENT