Highlights • AV7909 was safe and immunogenic when administered IM on Days 0 and 14. • AV7909 elicited a greater TNA response than BioThrax after 2 IM doses. • No significant difference was seen in ...immunogenicity of four AV7909 formulations. • Immunogenicity and reactogenicity of AV7909 will be studied further.
Dapivirine, a nonnucleoside reverse transcriptase inhibitor, is in development as a microbicide for the protection of women against HIV infection. A randomized, double-blind, phase 1 trial was ...conducted in 36 healthy HIV-negative women to compare the pharmacokinetics of 2 dapivirine vaginal gel formulations (0.05% each) and their safety with the hydroxyethyl cellulose-based universal placebo gel. Gel was self-administered once daily for a total of 11 days. Blood and vaginal fluid samples were collected sequentially over 24 days for pharmacokinetic analysis. Safety was evaluated by pelvic examination, colposcopy, adverse events, and clinical laboratory assessments. Adverse event profiles were similar for the 3 gels. Most events were mild and not related to study gel. Headache and vaginal hemorrhage (any vaginal bleeding) were most common. Plasma concentrations of dapivirine did not exceed 1.1 ng/mL. Steady-state conditions were reached within approximately 10 days. Dapivirine concentrations in vaginal fluids were slightly higher for Gel 4789, but Cmax values on days 1 and 14 were not significantly different. Terminal half-life was 72-73 hours in plasma and 15-17 hours in vaginal fluids. Both formulations of dapivirine gel were safe and well tolerated. Dapivirine was delivered to the lower genital tract at concentrations at least 5 logs greater than in vitro inhibitory concentrations.
Women and girls are especially vulnerable to HIV infection in sub-Saharan Africa, and in some of those countries, prevalence among young women can be up to 3 times higher than among men of the same ...age. Effective HIV prevention options for women are clearly needed in this setting. Several ARV-based vaginal microbicides are currently in development for prevention of HIV transmission to women and are discussed here. The concept of pre-exposure prophylaxis for the prevention of HIV transmission to women is introduced.
To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine ...microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) pg/mg.
Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.
Highlights • BioThrax was well tolerated. • The primary success criterion at Day 63 was met. • Key secondary success criteria at Day 70 and Days 63–100 were met.
PURPOSE OF REVIEWThe aim of this article is to summarize the latest information on microbicide formulations for prevention of sexual transmission of HIV infection in women.
RECENT FINDINGSAlthough ...early microbicide formulations were conventionally coitally dependent gel products, new technologies are being developed for vaginal delivery of anti-HIV agents. Intravaginal rings for delivery of microbicides, for example, are being developed and evaluated clinically. Safety and acceptability data are available for many microbicide gels and for one microbicide intravaginal ring. Other microbicide formulations in development for once daily or other vaginal administration strategies include films, tablets, and ovules. Various microbicide formulations for rectal administration are also in development.
SUMMARYNew microbicide formulations in development are addressing many of the issues with the original gels such as coital dependency, frequency of use, acceptability, compliance, cost, and adaptability to large-scale production. All of these dosage forms are promising options for safe, effective, and acceptable microbicide products.
The measurement of
K
∗
(
892
)
0
resonance production via its
K
+
π
-
decay mode in inelastic p+p collisions at beam momentum 158
Ge
V
/
c
(
s
NN
=
17.3
Ge
V
) is presented. The data were recorded ...by the NA61/SHINE hadron spectrometer at the CERN Super Proton Synchrotron. The
template
method was used to extract the
K
∗
(
892
)
0
signal and double-differential transverse momentum and rapidity spectra were obtained. The full phase-space mean multiplicity of
K
∗
(
892
)
0
mesons was found to be
(
78.44
±
0.38
(
stat
)
±
6.0
(
sys
)
)
·
10
-
3
. The NA61/SHINEresults are compared with the
Epos1.99
and Hadron Resonance Gas models as well as with world data from p+p and nucleus–nucleus collisions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Results on ϕ meson production in inelastic p+p collisions at CERN SPS energies are presented. They are derived from data collected by the NA61/SHINE fixed target experiment, by means of invariant ...mass spectra fits in the ϕ→K+K- decay channel. They include the first ever measured double differential spectra of ϕ mesons as a function of rapidity y and transverse momentum pT for proton beam momenta of 80GeV/c and 158GeV/c, as well as single differential spectra of y or pT for beam momentum of 40GeV/c. The corresponding total ϕ yields per inelastic p+p event are obtained. These results are compared with existing data on ϕ meson production in p+p collisions. The comparison shows consistency but superior accuracy of the present measurements. The emission of ϕ mesons in p+p reactions is confronted with that occurring in Pb+Pb collisions, and the experimental results are compared with model predictions. It appears that none of the considered models can properly describe all the experimental observations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Measurements of the Formula omitted, Formula omitted, and proton double differential yields emitted from the surface of the 90- Formula omitted-long carbon target (T2K replica) were performed for the ...incoming Formula omitted Formula omitted protons with the NA61/SHINE spectrometer at the CERN SPS using data collected during 2010 run. The double differential Formula omitted yields were measured with increased precision compared to the previously published NA61/SHINE results, while the Formula omitted and proton yields were obtained for the first time. A strategy for dealing with the dependence of the results on the incoming proton beam profile is proposed. The purpose of these measurements is to reduce significantly the (anti)neutrino flux uncertainty in the T2K long-baseline neutrino experiment by constraining the production of (anti)neutrino ancestors coming from the T2K target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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