Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 4: Clinical Vaccine Trials and Trial Site Challenges
P04.27 LB
First-In-Human Phase I Clinical Trial Of A
Recombinant Vesicular Stomatitis Virus (rVSV)-Based
Preventive HIV-1 Vaccine
J.D. Fuchs1 , I. Frank2 , N. Kochar3 , M. Elizaga3 , M. Allen4 ,
D. Carter3 , N. Frahm3 , S.A. Kalams5 , M. Mulligan6 , R. Sheets4 ,
M. Pensiero4 , D. Clarke7 , J. Eldridge7 , and the NIAID HIV Vaccine
Trials Network
1San Francisco Dept. of Public Health, San Francisco, CA,
USA; 2University of Pennsylvania, USA; 3Fred Hutchinson
Cancer Center, USA; 4Division of AIDS, NIH, USA; 5Vanderbilt University, USA; 6Emory University, USA; 7Profectus Biosciences, USA
Background: Replicating viral vectors are promising HIV
vaccine candidates that may enhance immunogenicity through
prolonged antigen expression. VSV is the first replicating viral
vector after vaccinia to be tested clinically as an HIV vaccine; here
we present preliminary safety and immunogenicity data from a
phase 1a trial.
Methods: HVTN 090 enrolled sixty healthy, HIV-1-uninfected
adults in a randomized, double-blinded, placebo-controlled dose
escalation study. Groups of 12 participants received rVSV Indiana
HIV Gag vaccine at 5 dose levels (4.6 x 103 to 3.4 x 107 PFU) (N=10/
group) or placebo (N=2/group), delivered intramuscularly at 0
and 2 months. Reactogenicity over 7 days, adverse events (AEs),
and viral cultures from whole blood, urine, saliva and swabs of
oral lesions were collected. HIV-1-specific CD4+ and CD8+ T-cell
responses to Gag peptides were measured 1 and 2 weeks postboost
by intracellular cytokine staining.
Results: The study is ongoing and data are blinded. The median
age was 24; 47% were female and 37% were non-white. Local
and systemic reactogenicity was self-limited, mild to moderate in
intensity and increased with dose, with headache reported most
commonly (52%). At the highest dose, 92% reported systemic
symptoms, including flu-like syndrome (41%), fever (41%), and
moderate chills (33%). Lymphadenopathy, decreased neutrophil
count, oral ulceration, and presyncope were each seen in > 1
participant. No severe reactogenicity, encephalitis, or productrelated
SAEs were reported, and all VSV cultures were negative
at all doses tested. Low frequency HIV-specific CD4+ (9%) and
CD8+ (3%) T-cell responses were detected post-boost at the first
3 dose levels.
Conclusion: Immunization with an attenuated, replicating rVSV
Indiana HIV-1 vaccine has an acceptable reactogencity and safety
profile to date. Preliminary data reveal few T-cell responses at
lower doses. Immunogenicity of the vaccine at the highest doses
and in heterologous prime-boost regimens will guide future
vector development.
162
AIDS Vaccine 2012
P04.28 LB
A Mixed-Methods Assessment Of Understanding
(AoU) Tool For AIDS Vaccine Trials In Sub-Saharan
Africa: Results From A Pilot Study
G. Lindegger 1 , M. Quayle 1 , S. Singh 2 , S. Welsh 7 , D. Mark 3 ,
M. Wallace 3 , S. Roux 3 , L. Bekker 3 , L. Mwananyanda 4 , W. Kilembe 4 ,
E. Chomba 5 , S. Allen 6 , F. Priddy 7 , P. Fast 7
1 School of Psychology, University of Kwa-Zulu Natal,
Pietermaritzburg, South Africa; 2 GHAR Consulting Inc, New
York, NY, USA; 3 Desmond Tutu HIV Foundation, University
of Cape Town, Cape Town, South Africa; 4 Zambia-Emory HIV
Research Project, Lusaka, Zambia; 5 Zambia-Emory HIV Reseach
Project, Lusaka, Zambia; 6 Emory University, Atlanta, GA, USA;
7 International AIDS Vaccine Initiative, New York, NY, USA
Background: Assessments of understanding (AoUs) in clinical
trials are often composed of true/false multiple choice questions,
however, these tools can be difficult for volunteers with limited
education or without prior testing experience.
Methods: 35 adults were recruited at two research centers in
Southern Africa. A within-subjects, repeated measures design
was used, whereby each volunteer served as his /her own
control. An AoU tool with closed- and open-ended questions
was administered within a hypothetical AIDS vaccine trial
setting. Performance on closed- and open-ended questions was
compared using correlations and repeated-measure t-tests,
limited to 4 complex concepts: false sense of security, risk of false
positive test, need for contraception, and potentially enhanced
susceptibility.
Results: Mean scores of understanding for each concept
assessed by closed-ended questions ranged from 0.73 (need for
contraception) to 0.84 (risk of false positive test); and by openended
questions from 0.4 (risk of false positive test) – 0.6 (need
for contraception). Scores for the open-ended measure were all
lower than the equivalent closed-ended measure. Correlations
between the closed- and open-ended measures were generally
low, achieving significance for false sense of security (r=0.377),
potentially enhanced susceptibility (r=0.393), and total score
across concepts (r=0.617). Volunteers’ understanding as assessed
by the closed- and open-ended methods differed significantly:
false sense of security= -3.862; risk of false positive test= -7.210;
need for contraception= -2.303; and potentially enhanced
susceptibility= -8.007. The correlation with years of education
was consistently and significantly higher for the open-ended
measure than the true/false questionnaire with the exception of
need for contraception.
Conclusion: The results suggest the qualitative measure
better assesses understanding than the quantitative measure.
The scores from the two assessment methods have limited
interchangeability. The standard closed-ended questions appear
to provide an inflated measure of volunteers’ understanding. An
assessment tool with closed- and open-ended questions is better
suited to determine genuine understanding.