Distance measurement by delayed optical feedback in a ring laser

We numerically study the behavior of a semiconductor ring laser subject to bidirectional delayed optical feedback, when the isolated laser is in the quasi-unidirectional regime. The optical feedback, provided by two external refectors located in front of the ring output waveguides, can modify the laser regime produced by the cross-saturation between the clockwise and the counter-clockwise mode. Thus, the system exhibits new diferent regimes, most of which are asymmetric and bidirectional, with alternating dominant mode. Two of these regimes are of special interest in view of applications, because the laser switching period, between the clockwise and the counter-clockwise mode, is linearly related to the time of fight from the laser to one or both refectors. In these operating conditions, the laser is thus suitable to implement a telemeter. A convenient electrical output signal is obtained by a photodiode located behind one (partially refecting) fxed mirror, or by measuring the voltage drop across the laser junction. Simulations are performed by mathematical models based on rate-equations, assuming typical literature parameters for a 1 mW ring laser

Impact of resistance mutations on virological efficacy of DTG-based maintenance two-drug regimens: an ARCA cohort study

Background: Two-drug regimens (2DR) are largely prescribed as maintenance therapy, nowadays mainly based on DTG. While many data have been reported about PI-based 2DR, the impact of resistance mutations and duration of virological suppression on DTG-based 2DR remains to be clarified. The aim of this study was to evaluate the impact of resistance mutations on virological outcome of DTG-based 2DR maintenance ART. Material and methods: Virologically suppressed patients (pts) switching to DTG+3TC or DTG+RPV with pre-baseline (time of switch=baseline, BL) resistance genotype (at least PR/RT) were selected from the ARCA database. Primary endpoint was virological failure (VF: an HIV-RNA, VL, >200 cps/mL or 2 consecutive >50 cps/mL). The probability of VF was estimated by Kaplan-Meier analysis. Resistance to 2DR was defined as occurrence of at least Stanford HIVdb (v.8.5) low-level resistance (LLR) to at least one drug included in the current 2DR, based on cumulative genotype. CD4 changes were assessed using Student’s t- test for paired samples. A secondary analysis comparing 2DR with DTG-based 3D regimens was also performed. Results: A total of 318 2DR pts were analysed: 260 (82%) switching to DTG+3TC, 58 (18%) to DTG+RPV; 68% were males, median age was 51 (44-56) years, 12 (6-23) years of HIV infection, 5 (3-8) years of virological suppression, nadir CD4 231 (121-329), 5 (3-9) previous ARV lines, 59% previously exposed to INSTI, 11% with resistance to current 2DR. The integrase sequence was available in 14% of patients, none harbouring resistance to DTG. 20 VF were observed, of whom 4 (3/17 VF in DTG+3TC, 1/3 in DTG+RPV) in patients with at least LLR at BL (M184V+K219Q; D67N+K70R+K219Q; D67N+K70R+T215Y+219Q; E138A), in a median FU of 1.3 years (IQR 0.6-2). The 2-year estimated probability of VF was 8.7% (95% CI 4.4;13); 8.6% (4.1;13.1) in those without resistance and 9.7% (-4.4;23.8) in those with resistance (Log rank: p=ns, figure 1). No factor was significantly associated with VF at multivariate analysis, but in pts with <6 years of virological suppression, BL resistance was associated with a higher probability of VF (p=0.003). After 48 weeks, a statistically significant increase in CD4+ was detected (+56 cells/mmc, p<0.001), independently from baseline resistance. The 2-year estimated probability of VF in the reference 3DR group (n=564) was not different from that for the 2DR group: 8.8% (5.9;11.7) in the whole case file and 9.7% (6.6;12.8) in the presence of baseline resistance. Longer time of virological suppression was the only factor associated with a lower risk of VF in the 3DR dataset. Conclusions: DTG-based 2DRs show high virological efficacy, even in the context of predicted incomplete activity, at least within a short-term follow-up. A longer duration of virological suppression seems to decrease the impact of resistance on virological outcome, however further studies are warranted to confirm this hypothesis and possibly define a clinically useful threshold