Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Measurement of CP asymmetries and branching fraction ratios of B− decays to two charm mesons

The $CP$ asymmetries of seven $B^-$ decays to two charm mesons are measured using data corresponding to an integrated luminosity of $9\text{fb}^{-1}$ of proton-proton collisions collected by the LHCb experiment. Decays involving a $D^{*0}$ or $D^{*-}_s$ meson are analysed by reconstructing only the $D^0$ or $D^-_s$ decay products. This paper presents the first measurement of $\mathcal{A}^{CP}(B^- \rightarrow D^{*-}_s D^0)$ and $\mathcal{A}^{CP}(B^- \rightarrow D^{-}_s D^{*0})$, and the most precise measurement of the other five $CP$ asymmetries. There is no evidence of $CP$ violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured.The CP asymmetries of seven B$^{−}$ decays to two charm mesons are measured using data corresponding to an integrated luminosity of 9 fb$^{−1}$ of proton-proton collisions collected by the LHCb experiment. Decays involving a D$^{*0}$ or ${D}_s^{\ast -}$ meson are analysed by reconstructing only the D$^{0}$ or ${D}_s^{-}$ decay products. This paper presents the first measurement of $\mathcal{A} ^{CP}$(B$^{−}$→${D}_s^{\ast -}$D$^{0}$) and $\mathcal{A} ^{CP}$(B$^{−}$→${D}_s^{-}$D$^{∗0}$), and the most precise measurement of the other five CP asymmetries. There is no evidence of CP violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured.[graphic not available: see fulltext]The $CP$ asymmetries of seven $B^-$ decays to two charm mesons are measured using data corresponding to an integrated luminosity of $9\text{ fb}^{-1}$ of proton-proton collisions collected by the LHCb experiment. Decays involving a $D^{*0}$ or $D^{*-}_s$ meson are analysed by reconstructing only the $D^0$ or $D^-_s$ decay products. This paper presents the first measurement of $\mathcal{A}^{CP}(B^- \rightarrow D^{*-}_s D^0)$ and $\mathcal{A}^{CP}(B^- \rightarrow D^{-}_s D^{*0})$, and the most precise measurement of the other five $CP$ asymmetries. There is no evidence of $CP$ violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured

Study of the lineshape of the chi(c1) (3872) state

A study of the lineshape of the chi(c1) (3872) state is made using a data sample corresponding to an integrated luminosity of 3 fb(-1) collected in pp collisions at center-of-mass energies of 7 and 8 TeV with the LHCb detector. Candidate chi(c1)(3872) and psi(2S) mesons from b-hadron decays are selected in the J/psi pi(+)pi(-) decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the chi(c1 )(3872) and psi(2S) states, Delta m, and the width of the chi(c1 )(3872) state, Gamma(Bw), are determined to be (Delta m=185.598 +/- 0.067 +/- 0.068 Mev,)(Gamma BW=1.39 +/- 0.24 +/- 0.10 Mev,) where the first uncertainty is statistical and the second systematic. Using a Flatte-inspired model, the mode and full width at half maximum of the lineshape are determined to be (mode=3871.69+0.00+0.05 MeV.)(FWHM=0.22-0.04+0.13+0.07+0.11-0.06-0.13 MeV, ) An investigation of the analytic structure of the Flatte amplitude reveals a pole structure, which is compatible with a quasibound D-0(D) over bar*(0) state but a quasivirtual state is still allowed at the level of 2 standard deviations

Measurement of the CKM angle γγ in B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm \to D π^\pm decays with D→KS0h+h−D \to K_\mathrm S^0 h^+ h^-

A measurement of $CP$-violating observables is performed using the decays $B^\pm\to D K^\pm$ and $B^\pm\to D \pi^\pm$, where the $D$ meson is reconstructed in one of the self-conjugate three-body final states $K_{\mathrm S}\pi^+\pi^-$ and $K_{\mathrm S}K^+K^-$ (commonly denoted $K_{\mathrm S} h^+h^-$). The decays are analysed in bins of the $D$-decay phase space, leading to a measurement that is independent of the modelling of the $D$-decay amplitude. The observables are interpreted in terms of the CKM angle $\gamma$. Using a data sample corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$ collected in proton-proton collisions at centre-of-mass energies of $7$, $8$, and $13\,\text{TeV}$ with the LHCb experiment, $\gamma$ is measured to be $\left(68.7^{+5.2}_{-5.1}\right)^\circ$. The hadronic parameters $r_B^{DK}$, $r_B^{D\pi}$, $\delta_B^{DK}$, and $\delta_B^{D\pi}$, which are the ratios and strong-phase differences of the suppressed and favoured $B^\pm$ decays, are also reported

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

Measurement of psi (2S) production cross-sections in proton-proton collisions at v s=7 and 13 TeV

The cross-sections of \u3c8(2 S) meson production in proton-proton collisions at s=13TeV are measured with a data sample collected by the LHCb detector corresponding to an integrated luminosity of 275pb-1. The production cross-sections for prompt \u3c8(2 S) mesons and those for \u3c8(2 S) mesons from b-hadron decays (\u3c8(2S)-from-b) are determined as functions of the transverse momentum, pT, and the rapidity, y, of the \u3c8(2 S) meson in the kinematic range 2&lt;20GeV/c and 2.0 &lt; y&lt; 4.5. The production cross-sections integrated over this kinematic region are \u3c3(prompt\u3c8(2S),13TeV)=1.430\ub10.005(stat)\ub10.099(syst)\u3bcb,\u3c3(\u3c8(2S)-from-b,13TeV)=0.426\ub10.002(stat)\ub10.030(syst)\u3bcb.A new measurement of \u3c8(2 S) production cross-sections in pp collisions at s=7TeV is also performed using data collected in 2011, corresponding to an integrated luminosity of 614pb-1. The integrated production cross-sections in the kinematic range 3.5&lt;14GeV/c and 2.0 &lt; y&lt; 4.5 are \u3c3(prompt\u3c8(2S),7TeV)=0.471\ub10.001(stat)\ub10.025(syst)\u3bcb,\u3c3(\u3c8(2S)-from-b,7TeV)=0.126\ub10.001(stat)\ub10.008(syst)\u3bcb.All results show reasonable agreement with theoretical calculations

Measurement of the eta(c)(1S) production cross-section in p p collisions at root s=13TeV

Using a data sample corresponding to an integrated luminosity of 2.0 fb-1, collected by the LHCb experiment, the production of the \u3b7c(1 S) state in proton\u2013proton collisions at a centre-of-mass energy of s=13TeV is studied in the rapidity range 2.0 &lt; y&lt; 4.5 and in the transverse momentum range 6.5&lt;14.0GeV. The cross-section for prompt production of \u3b7c(1 S) mesons relative to that of the J/ \u3c8 meson is measured using the pp\uaf decay mode and is found to be \u3c3\u3b7c(1S)/\u3c3J/\u3c8=1.69\ub10.15\ub10.10\ub10.18. The quoted uncertainties are, in order, statistical, systematic and due to uncertainties on the branching fractions of the J/\u3c8\u2192pp\uaf and \u3b7c\u2192pp\uaf decays. The prompt \u3b7c(1 S) production cross-section is determined to be \u3c3\u3b7c(1S)=1.26\ub10.11\ub10.08\ub10.14\u3bcb, where the last uncertainty includes that on the J/ \u3c8 meson cross-section. The ratio of the branching fractions of b-hadron decays to the \u3b7c(1 S) and J/ \u3c8 states is measured to be Bb\u2192\u3b7cX/Bb\u2192J/\u3c8X=0.48\ub10.03\ub10.03\ub10.05, where the last uncertainty is due to those on the branching fractions of the J/\u3c8\u2192pp\uaf and \u3b7c\u2192pp\uaf decays. The difference between the J/ \u3c8 and \u3b7c(1 S) masses is also determined to be 113.0\ub10.7\ub10.1MeV, which is the most precise single measurement of this quantity to date

Measurement of the D∗D^* longitudinal polarization in B0→D∗−τ+ντB^0 \to D^{* -}\tau^+\nu_{\tau} decays

The longitudinal polarization fraction of the $D^*$ meson is measured in $B^0 \to D^{* -}\tau^+\nu_{\tau}$ decays, where the $\tau$ lepton decays to three charged pions and a neutrino, using proton-proton collision data collected by the LHCb experiment at center-of-mass energies of 7, 8 and 13 TeV and corresponding to an integrated luminosity of 5 fb$^{-1}$. The $D^*$ polarization fraction $F_L^{D^*}$ is measured in two $q^2$ regions, below and above 7 GeV$^2$/c$^4$, where $q^2$ is defined as the squared invariant mass of the $\tau\nu_{\tau}$ system. The $F_L^{D^*}$ values are measured to be $0.51 \pm 0.07 \pm 0.03$ and $0.35 \pm 0.08 \pm 0.02$ for the lower and higher $q^2$ regions, respectively. The first uncertainties are statistical and the second systematic. The average value over the whole $q^2$ range is: $$F_L^{D^*} = 0.43 \pm 0.06 \pm 0.03.$$ These results are compatible with the Standard Model predictions.The longitudinal polarization fraction of the $D^{*}$ meson is measured in $B^0\to D^{*-}\tau^{+}\nu_{\tau}$ decays, where the $\tau$ lepton decays to three charged pions and a neutrino, using proton-proton collision data collected by the LHCb experiment at center-of-mass energies of 7, 8 and 13 TeV and corresponding to an integrated luminosity of 5 fb$^{-1}$. The $D^{*}$ polarization fraction $F_{L}^{D^{*}}$ is measured in two $q^{2}$ regions, below and above 7 GeV$^{2}/c^{4}$, where $q^{2}$ is defined as the squared invariant mass of the $\tau\nu_{\tau}$ system. The $F_{L}^{D^{*}}$ values are measured to be $0.51 \pm 0.07 \pm 0.03$ and $0.35 \pm 0.08 \pm 0.02$ for the lower and higher $q^{2}$ regions, respectively. The first uncertainties are statistical and the second systematic. The average value over the whole $q^{2}$ range is: $$F_{L}^{D^{*}} = 0.43 \pm 0.06 \pm 0.03.$$ These results are compatible with the Standard Model predictions