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

90 Abstracts WePeB6047-WePeB6050

XIV International AIDS Conference

WePeB6047 Incidence of HPV related cervical lesions in HIV
positive/ Pap Test negative women undergoing
different antiretroviral treatments
F. Lillo', S. Lodini', M. Origoni', G.L. Taccagni', F. Veglia2, D. Ferrari1,
C. Uberti Foppal. 'IRCCS-HSR, via Stamira DAncona 20, milano, Italy;
2Institute for Scientific Intechange foundation, Torino, Italy
Background: HR-HPV cervical infection more frequently evolve in cytohystological lesion in immunocompromised host. We evaluated whether different antiretroviral treatments influence the gynaecological outcome of HIV positive
women with a negative baseline Pap Test.
Methods: 125 women with a negative baseline Pap Test have been enrolled in
a prospective study on the incidence of cervical disease. Visits, at 6 months intervals, included CD4 cell count, HIV viremia, Pap Test, HPV DNA detection and
typing and colposcopy, with biopsy if necessary.
Results: During the observation period (mean 39.9 months, range 6-61.5
months), 71 women were treated with 2 reverse trascriptase inhibitors (RT), 23
with Highly Active Antiretroviral Therapy (HAART-PI) and 36 where untreated
(NT). CD4 cell count increased significantly only in women receiving HAART. The
incidence of hystological Squamous Intraepitelial Lesions (SIL) was similar in the
three groups (NT=8.5%, RT 4.2% PI =10.8%). The Cox model confirmed that the
risk of developing any type of histological lesion was not different in the three
groups of HIV therapy (RR for RT therapy= 0.7, Cl: 0.16-3.12; for PI therapy=
0.75, CI: 0.34.1.68) All these women were HR-HPV positive at baseline by HC or
PCR detection.
Conclusions: These results indicate that even in the era of HAART, HIV positive
women are at higher risk of developing high grade lesions and cervical cancer.
Dedicated monitoring protocols including HPV typing are probably needed to better prevent neoplastic evolution
Presenting author: flavia lillo, via Stamira D'Ancona 20, milano, Italy, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
WePeB6048 Evaluation of the preparedness for Phase I HIV-1
Vaccine trials in Uganda
E. Mugishal, P. Kaleebu2, L. Nielsen', M. Sweat3, G. Thiry4, C. Schmidt4,
B. Levings4. 1UVRI-IAVI HIV Vaccine Program, International AIDS Vaccine
Initiative (IAV/-UVRI HIV Vaccine Program, P 0. Box 22616, Kampala, Uganda;
2 UVRI-IAVI HIV Vaccine Program/MRC-UVRI Program on AIDS in Uganda,
Kampala, Uganda; 3Johns Hopkins University School of Public Health,
Baltimore, Maryland, United States; International AIDS Vaccine Initiative (IAVI),
New York, United States
Background: As millions in developing countries become infected with HIV and
as the cost of HIV treatment remains prohibitive to many, the hope against the epidemic is an effective vaccine. Phase I trials require baseline studies into knowledge and willingness to participate (WTP). The objectives of the study were to
assess levels of understanding of vaccines, clinical trials and WTP in vaccine
trials among schoolteachers in Entebbe, south-central Uganda.
Methods: The study used a standardized survey instrument. Bi-variate and multivariate analysis using odds ratio (OR). Simple and multiple logistic regression
analysis were run using STATA.
Results: The study group comprised 100 participants, of whom 58% were females. The median age was 29.6 years. The majority of the participants (65%)
were married, 31% never married, and "other" 4%. Seventy percent indicated
that the HIV/AIDS epidemic is "very serious" in Uganda, while the rest indicated
HIV is "somewhat serious", and nobody said "not serious". The majority (62%)
perceived themselves to be at no risk of acquiring HIV, and lifetime use of a condom was 69%. Eighty-one percent had heard about vaccine development efforts
and a similar proportion (81%) were willing to participate in an hypothetical HIV
vaccine trial. Perceptions and attitudes towards HIV vaccines and WTP in a trial
varied by sex, age and marital status. Married people were more WTP compared
to unmarried (p 0.04). Perceived risk of HIV did not influence WTP (p >0.05).
Although perceived benefits did not influence WTP, perceived risk of the vaccine
did influence WTP (p 0.001).
Conclusion: In Uganda, awareness about the magnitude of the AIDS epidemic
and its impact is high and the need for an AIDS vaccine is urgent. Knowledge
about HIV vaccine trials is high and there is no stigma associated with participation. WTP in vaccine trials is highly influenced by the level of knowledge about
trial vaccines and perceived risk of the trial vaccine.
Presenting author: Emmanuel Mugisha, International AIDS Vaccine Initiative
(IAVI-UVRI HIV Vaccine Program, P. O. Box 22616, Kampala, Uganda, Tel.: [phone], Fax: [phone], E-mail: [email protected]

WePeB6049 Safety and immunogenicity of live recombinant
ALVAC-HIV (vCP1521) priming with AIDSVAX~ BIE
gpl20 boosting in Thai HIV-negative adults
S. Nitayaphan', P. Pitisuttithum2, M. de Souza', J. Kim3, V. Polonis3,
W. Heyward4, S. Gurunathan5, S. Ratto-Kim3, A. Brown', A.N.D. Thai AIDS
Vaccine Evaluation Group 6. 'Armed Forces Research Institute of Medical
Sciences, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi
Road, Bangkok, 10400, Thailand; 2Faculty of Tropical Medicine, Mahidol
University Bangkok, Thailand; 3 Walter Reed Army Institute of Research,
Rockville, United States; 4 VaxGen, Brisbane, United States; 5Aventis Pasteur,
Lyon, France; 6 TAVEG, Bangkok, Thailand
Background: The first safety and immunogenicity trial of ALVAC-HIV vCP1521
prime with an AIDSVAX B/E gpl20 boost was conducted in Thailand. vCP1521 is
a recombinant canarypox vector vaccine that has been genetically engineered to
express subtype E HIV-1 gpl120 (92TH023) linked to transmembrane anchoring
portion of gp41, and HIV-1 gag and protease (LAI strain). AIDSVAX B/E is a recombinant bivalent HIV gpl20 envelope glycoprotein vaccine. The ALVAC-HIV +
AIDSVAX B/E prime-boost combination is currently being evaluated for possible
advancement to phase III efficacy testing in Thailand.
Methods: The study was a double-blind, randomized, placebo-controlled phase
II trial. Volunteers were enrolled and divided into two groups based on the dose
of AIDSVAX B/E, and subjects were randomized to vaccine or placebo in a ratio of 3:1. 45 low-risk, HIV-seronegative Thai adults from each group were given
ALVAC-HIV (vCP1521, 106.5CCID50) at weeks 0, 4, 12 and 24. At weeks 12 and
24, 200ug or 600ug of bivalent AIDSVAX B/E (100ug or 300ug of each antigen)
was given. 15 other subjects from each group received placebo injections.
Results: Most reactogenicity was mild to moderate and comparable to previous
studies of similar prime-boost combinations and adjuvant. Seven serious adverse
events were reported, none attributable to vaccine. Among recipients of the 600
ug dose of AIDSVAX B/E boost, 71% and 98% of vaccine recipients had neutralizing antibody to subtype E and B TCLA HIV strains. HIV-specific CTL response
is being analyzed. Among recipients of the 600 ug dose of AIDSVAX B/E boost,
71% had lymphocyte proliferation to gpl20 CM244, while 49% had proliferation
to gpl20 MN.
Conclusions: Prime-boost vaccination with ALVAC-HIV and AIDSVAX B/E appears safe and well-tolerated. This prime-boost combination induces both humoral and cellular HIV-specific immune responses. It is an appropriate candidate
for advancement to Phase Ill evaluation.
Presenting author: Sorachai Nitayaphan, Armed Forces Research Institute of
Medical Sciences, 315/6 Rajvithi Road, Bangkok, 10400, Thailand, Tel.: +66 2
644 6765, Fax: [phone], E-mail: [email protected]
WePeB6050O Single dose pharmacokinetics of SPD-756 in
healthy adult volunteers
P.F. Smith', A. Forrest', C.H. Ballow2, J.M. Adams3, L.R. Shiveley4. 'University
at Buffalo School of Pharmacy, Buffalo, NY; 2Buffalo CRC, Buffalo, NY,
3 PharmaResearch, Morrisville, NC; 4Shire Pharmaceutical Development Inc.,
Rockville, MD, United States
Background: SPD-756 (formerly BCH-13520) is a novel nucleoside reverse transcriptase inhibitor in Phase I development. Our objective was to determine the
pharmacokinetics (PK) of single oral doses of SPD-756 in healthy volunteers.
Methods: 38 healthy men were enrolled in a randomized double-blind Phase I
dose-escalation study; cohorts (n) received single 100(6), 200(6), 400(6), 800(6),
or 1200(5) mg oral doses of SPD-756 or placebo (9) while fasted. Frequent
plasma & urine samples were collected in all subjects up to 72hr after dosing
& assayed by validated LC/MS. Plasma & urine data were analyzed by noncompartmental methods & by fitting PK models, using maximum likelihood followed
by Bayesian estimation (Adapt II). Model discrimination was by Akaike's Information Criterion. Kruskal-Wallis was used to test for significant differences in PK
parameters by dose.
Results: SPD-756 was well absorbed, with a median Tmax ranging from 0.75 -1.25h for all cohorts. Other mean (CV%) parameters are reported in the table
below. Dose-normalized Cmax & renal clearance (CLr) did not change with dose
(p>0.05), while average oral clearance (Dose/AUC) decreased with dose, & was
non-linear (p<0.05). The final PK model had multi-phasic 1st order absorption,
central & peripheral distribution volumes, 1st order distributional, renal & nonrenal clearances, & a saturable non-renal clearance. At higher doses, ~.2/3 of a
dose is cleared renally, 25% by the saturable pathway & 10% by the 1st order
non-renal clearance. Larger doses had a mean (CV%) apparent plasma half-life
of 2.8(41) h. CLr is significantly larger than normal glomerular filtration, suggesting active renal secretion.
Cohort (mg) 100 200 400 800 1200
Cmax (ng/mL) 1261 (42) 1655(36) 3947(63) 9558(70) 12348(17)
Dose/AUC (L/h) 72.0(29) 74.0(39) 76.4(62) 34.0(23) 29.0(10)

AUC (ng*h/mL) 1498(32) 3021(56) 7157(56) 24687(25) 41794(11)
CLr (L/h) 19.9(16) 23.5(15) 22.6(22) 19.8(24) 16.6(11)
Conclusions: SPD-756 is well absorbed after oral dosing, & exhibits concentrations significantly higher than the in vitro IC50(64ng/mL) against wild-type HIV
virus. SPD-756 exhibits a significant degree of renal & non-renal elimination, with
a portion of its non-renal metabolism being saturable.