23 research outputs found
Profile of etravirine for the treatment of HIV infection
Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with the advantages of in vitro potency against many strains of virus resistant to efavirenz and nevirapine, as well as a higher genetic barrier to resistance. Etravirine is indicated for use in treatment-experienced patients, and the approved dose in adults is 200 mg twice daily. Etravirine should be administered after a meal as bioavailability is significantly reduced when taken in the fasting state. Etravirine is a substrate of CYP3A4, CYP2C9, CYP2C19, and uridine diphosphate glucuronyltransferase, and induces CYP3A4, weakly inhibits CYP2C9 and moderately inhibits CYP2C19. Etravirine may be coadministered with nucleoside/tide reverse transcriptase inhibitors, raltegravir and boosted darunavir, lopinavir, and saquinavir without dosage adjustment. Etravirine should not be given with other NNRTIs, unboosted protease inhibitors, and atazanavir/ritonavir, tipranavir/ritonavir, and fosamprenavir/ritonavir due to unfavorable drug interactions. In randomized, controlled trials, twice daily etravirine combined with darunavir/ritonavir plus optimized background therapy demonstrated better efficacy compared to darunavir/ritonavir plus optimized background therapy alone in treatment-experienced populations out to 96 weeks follow-up. The main etravirine-associated toxicity is mild to moderate self-limiting rash, although severe and sometimes fatal hypersensitivity reactions have been reported. Etravirine offers a potent sequencing option after the development of resistance to first-line NNRTIs, and is a welcome addition to this established drug class
Treatment with lamivudine, zidovudine, or both in hiv-positive patients with 200 to 500 cd4+ cells per cubic millimeter
Background. The reverse-transcriptase inhibitor
lamivudine has in vitro synergy with zidovudine
against the human immunodeficiency virus (HIV). We
studied the activity and safety of lamivudine plus zidovudine
as compared with either drug alone as treatment for
patients with HIV infection, most of whom had not previously
received zidovudine.
Methods. Three hundred sixty-six patients with 200
to 500 CD4+ cells per cubic millimeter who had received
zidovudine for four weeks or less were randomly assigned
to treatment with one of four regimens: 300 mg of
lamivudine every 12 hours; 200 mg of zidovudine every
8 hours; 150 mg of lamivudine every 12 hours plus zidovudine;
or 300 mg of lamivudine every 12 hours plus zidovudine.
The study was double-blind and lasted 24
weeks, with an extension phase for another 28 weeks.
Results. Over the 24-week period, the low-dose and
high-dose regimens combining lamivudine and zidovudine
were associated with greater increases in the
CD4+ cell count (P=0.002 and P=0.015, respectively)
and the percentage of CD4+ cells (P<0.001 for both)
and with greater decreases in plasma levels of HIV type
1 (HIV-1) RNA (P<0.001 for both) than was treatment
with zidovudine alone. Combination therapy was also
more effective than lamivudine alone in lowering plasma
HIV-1 RNA levels and increasing the percentage of
CD4+ cells (P<0.001 for all comparisons), and these advantages
persisted through 52 weeks. Adverse events
were no more frequent with combination therapy than
with zidovudine alone.
Conclusions. In HIV-infected patients with little or no
prior antiretroviral therapy, treatment with a combination
of lamivudine and zidovudine is well tolerated over a oneyear
period and produces more improvement in immunologic
and virologic measures than does treatment with either
agent alone. (N Engl J Med 1995;333:1662-9.
A search of the Orion spur for continuous gravitational waves using a "loosely coherent" algorithm on data from LIGO interferometers
We report results of a wideband search for periodic gravitational waves from
isolated neutron stars within the Orion spur towards both the inner and outer
regions of our Galaxy. As gravitational waves interact very weakly with matter,
the search is unimpeded by dust and concentrations of stars. One search disk
(A) is in diameter and centered on
, and the other
(B) is in diameter and centered on
. We explored the
frequency range of 50-1500 Hz and frequency derivative from to Hz/s. A multi-stage, loosely coherent search program allowed probing
more deeply than before in these two regions, while increasing coherence length
with every stage.
Rigorous followup parameters have winnowed initial coincidence set to only 70
candidates, to be examined manually. None of those 70 candidates proved to be
consistent with an isolated gravitational wave emitter, and 95% confidence
level upper limits were placed on continuous-wave strain amplitudes. Near
Hz we achieve our lowest 95% CL upper limit on worst-case linearly polarized
strain amplitude of , while at the high end of our
frequency range we achieve a worst-case upper limit of for
all polarizations and sky locations.Comment: Fixed minor typo - duplicate name in the author lis
Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers
We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society
First low frequency all-sky search for continuous gravitational wave signals
In this paper we present the results of the first low frequency all-sky search of continuous gravitational wave signals conducted on Virgo VSR2 and VSR4 data. The search covered the full sky, a frequency range between 20 and 128 Hz with a range of spin-down between −1.0×10−10 and +1.5×10−11 Hz/s, and was based on a hierarchical approach. The starting point was a set of short fast Fourier transforms, of length 8192 s, built from the calibrated strain data. Aggressive data cleaning, in both the time and frequency domains, has been done in order to remove, as much as possible, the effect of disturbances of instrumental origin. On each data set a number of candidates has been selected, using the FrequencyHough transform in an incoherent step. Only coincident candidates among VSR2 and VSR4 have been examined in order to strongly reduce the false alarm probability, and the most significant candidates have been selected. The criteria we have used for candidate selection and for the coincidence step greatly reduce the harmful effect of large instrumental artifacts. Selected candidates have been subject to a follow-up by constructing a new set of longer fast Fourier transforms followed by a further incoherent analysis, still based on the FrequencyHough transform. No evidence for continuous gravitational wave signals was found, and therefore we have set a population-based joint VSR2-VSR4 90% confidence level upper limit on the dimensionless gravitational wave strain in the frequency range between 20 and 128 Hz. This is the first all-sky search for continuous gravitational waves conducted, on data of ground-based interferometric detectors, at frequencies below 50 Hz. We set upper limits in the range between about 10−24 and 2×10−23 at most frequencies. Our upper limits on signal strain show an improvement of up to a factor of ∼2 with respect to the results of previous all-sky searches at frequencies below 80 H
Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers
We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20[superscript h]10[superscript m]54.71[superscript s] + 33°33[superscript ′]25.29[superscript ′′], and the other (B) is 7.45° in diameter and centered on 8[superscript h]35[superscript m]20.61[superscript s] - 46°49[superscript ′]25.151[superscript ′′]. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to -5 × 10[superscript -9] Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h[subscript 0] of 6.3 × 10[superscript -25], while at the high end of our frequency range we achieve a worst-case upper limit of 3.4 × 10[superscript -24] for all polarizations and sky locations.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio
Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers
We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20[superscript h]10[superscript m]54.71[superscript s] + 33°33[superscript ′]25.29[superscript ′′], and the other (B) is 7.45° in diameter and centered on 8[superscript h]35[superscript m]20.61[superscript s] - 46°49[superscript ′]25.151[superscript ′′]. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to -5 × 10[superscript -9] Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h[subscript 0] of 6.3 × 10[superscript -25], while at the high end of our frequency range we achieve a worst-case upper limit of 3.4 × 10[superscript -24] for all polarizations and sky locations.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio