Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort.

OBJECTIVES: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. METHODS: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. RESULTS: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. CONCLUSIONS: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

Regularized linearization for quantum nonlinear optical cavities: application to degenerate optical parametric oscillators.

Nonlinear optical cavities are crucial both in classical and quantum optics; in particular, nowadays optical parametric oscillators are one of the most versatile and tunable sources of coherent light, as well as the sources of the highest quality quantum-correlated light in the continuous variable regime. Being nonlinear systems, they can be driven through critical points in which a solution ceases to exist in favour of a new one, and it is close to these points where quantum correlations are the strongest. The simplest description of such systems consists in writing the quantum fields as the classical part plus some quantum fluctuations, linearizing then the dynamical equations with respect to the latter; however, such an approach breaks down close to critical points, where it provides unphysical predictions such as infinite photon numbers. On the other hand, techniques going beyond the simple linear description become too complicated especially regarding the evaluation of two-time correlators, which are of major importance to compute observables outside the cavity. In this article we provide a regularized linear description of nonlinear cavities, that is, a linearization procedure yielding physical results, taking the degenerate optical parametric oscillator as the guiding example. The method, which we call self-consistent linearization, is shown to be equivalent to a general Gaussian ansatz for the state of the system, and we compare its predictions with those obtained with available exact (or quasi-exact) methods. Apart from its operational value, we believe that our work is valuable also from a fundamental point of view, especially in connection to the question of how far linearized or Gaussian theories can be pushed to describe nonlinear dissipative systems which have access to non-Gaussian states.

Noncritical quadrature squeezing through spontaneous polarization symmetry breaking.

We discuss the possibility of generating noncritical quadrature squeezing by spontaneous polarization symmetry breaking. We first consider Type II frequency-degenerate optical parametric oscillators but discard them for a number of reasons. Then we propose a four-wave-mixing cavity, in which the polarization of the output mode is always linear but has an arbitrary orientation. We show that in such a cavity, complete noise suppression in a quadrature of the output field occurs, irrespective of the parameter values.

Diffusion stabilizes cavity solitons in bidirectional lasers.

We study the influence of field diffusion on the spatial localized structures (cavity solitons) in bidirectional lasers. We find threefold positive role of the diffusion: 1) it allows for the existence of solitons in cavities with equal losses for the two fields; 2) it increases the stability range of the individual (isolated) solitons; and 3) it reduces the long-range interaction between cavity solitons, allowing for the independent manipulation (writing and erasing) of individual structures.

Noncritically squeezed light via spontaneous rotational symmetry breaking.

We predict squeezed light generation through the spontaneous rotational symmetry breaking occurring in a degenerate optical parametric oscillator (DOPO) pumped above threshold. We show, within the linearized theory, that a DOPO with spherical mirrors, in which the signal and idler fields correspond to first-order Laguerre-Gauss modes, produces a perfectly squeezed vacuum with the shape of a Hermite-Gauss mode. This occurs at any pumping level above threshold; hence, the phenomenon is noncritical. Imperfections of the rotational symmetry, due, e.g., to cavity anisotropy, are shown to have a small impact.

Cavity solitons in bidirectional lasers.

We show theoretically that a broad area bidirectional laser with slightly different cavity losses for the two counterpropagating fields sustains cavity solitons (CSs). These are complementary; i.e., there is a bright (dark) CS in the field with larger (smaller) losses. Interestingly, the CSs can be written or erased by injecting suitable pulses into any of the two counterpropagating fields.

Bistable phase locking of a nonlinear optical cavity via rocking: Transmuting vortices into phase patterns.

We report the experimental observation of the conversion of a phase-invariant nonlinear system into a bistable phase-locked one via rocking [G. J. de Valcárcel and K. Staliunas, Phys. Rev. E 67, 026604 (2003)10.1103/PhysRevE.67.026604]. This conversion results in vortices of the phase-invariant system being replaced by phase patterns such as domain walls. A model for the experimental device, a photorefractive oscillator, is given that reproduces the observed behavior.

Hysteretic nonequilibrium Ising-Bloch transition.

We show that a parametrically driven cubic-quintic complex Ginzburg-Landau equation exhibits a hysteretic nonequilibrium Ising-Bloch transition for large enough quintic nonlinearity. These results help to understand the recent experimental observation of this phenomenon [A. Esteban-Martín, Phys. Rev. Lett. 94, 223903 (2005)].

Domain wall dynamics in an optical Kerr cavity.

An anisotropic (dichroic) optical cavity containing a self-focusing Kerr medium is shown to display a bifurcation between static--Ising--and moving--Bloch--domain walls, the so-called nonequilibrium Ising-Bloch transition (NIB). Bloch walls can show regular or irregular temporal behavior, in particular, bursting and spiking. These phenomena are interpreted in terms of the spatiotemporal dynamics of the extended patterns connected by the wall, which display complex dynamical behavior as well. Domain wall interaction, including the formation of bound states is also addressed.

Controlled observation of a nonequilibrium Ising-Bloch transition in a nonlinear optical cavity.

We report the controlled observation of the nonequilibrium Ising-Bloch transition in a broad area nonlinear optical cavity (a quasi-1D single longitudinal-mode photorefractive oscillator in a degenerate four-wave mixing configuration). Our experimental technique allows for the controlled injection of the domain walls. We use cavity detuning as control parameter and find that both Ising and Bloch walls can exist for the same detuning values within a certain interval of detunings; i.e., the Ising-Bloch transition is hysteretic in our case. A complex Ginzburg-Landau model is used for supporting the observations.

Control and steering of phase domain walls.

We show experimentally the feasibility of optically controlled location, individual addressing/erasure and steering of phase domain walls by injection of coherent addressing pulses into a phase-locked four-wave-mixing photorefractive oscillator.

Stabilizing and controlling domain walls and dark-ring cavity solitons.

We demonstrate two alternative techniques for controlling and stabilizing domain walls (DW) in phase-sensitive, nonlinear optical resonators. The first of them uses input pumps with spatially modulated phase and can be applied also to dark-ring cavity solitons. An optical memory based on the latter is demonstrated. Here the physical mechanism of control relies on the advection caused to any feature by the phase gradients. The second technique uses a plane wave input pump with holes of null intensity across its transverse plane, which are able to capture DWs. Here the physical mechanism of control is of topological nature. When distributed as a regular array, these holes delimit spatial optical bits which constitute an optical memory. These techniques are illustrated in a degenerate optical parametric oscillator model, but can be applied to any phase-sensitive nonlinear optical cavity.

Domain walls and ising-BLOCH transitions in parametrically driven systems.

Parametrically driven systems sustaining sech solitons are shown to support a new kind of localized state. These structures are walls connecting two regions oscillating in antiphase that form in the parameter domain where the sech soliton is unstable. Depending on the parameter set the oppositely phased domains can be either spatially uniform or patterned. Both chiral (Bloch) and nonchiral (Ising) walls are found, which bifurcate one into the other via an Ising-Bloch transition. While Ising walls are at rest Bloch walls move and may display secondary bifurcations leading to chaotic wall motion.