Week 96 Extension Results of a Phase 3 Study Evaluating Long-Acting Cabotegravir with Rilpivirine for HIV-1 Treatment

BACKGROUND: ATLAS (NCT02951052), a phase 3, multicenter, open-label study, demonstrated that switching to injectable cabotegravir (CAB) with rilpivirine (RPV) long-acting dosed every 4 weeks was noninferior at week (W) 48 to continuing three-drug daily oral current antiretroviral therapy (CAR). Results from the W 96 analysis are presented. METHODS AND DESIGN: Participants completing W 52 of ATLAS were given the option to withdraw, transition to ATLAS-2M (NCT03299049), or enter an Extension Phase to continue long-acting therapy (Long-acting arm) or switch from CAR to long-acting therapy (Switch arm). Endpoints assessed at W 96 included proportion of participants with plasma HIV-1 RNA less than 50 copies/ml, incidence of confirmed virologic failure (CVF; two consecutive HIV-1 RNA ≥200 copies/ml), safety and tolerability, pharmacokinetics, and patient-reported outcomes. RESULTS: Most participants completing the Maintenance Phase transitioned to ATLAS-2M (88%, n = 502/572). Overall, 52 participants were included in the W 96 analysis of ATLAS; of these, 100% (n = 23/23) and 97% (n = 28/29) in the Long-acting and Switch arms had plasma HIV-1 RNA less than 50 copies/ml at W 96, respectively. One participant had plasma HIV-1 RNA 50 copies/ml or higher in the Switch arm (173 copies/ml). No participants met the CVF criterion during the Extension Phase. No new safety signals were identified. All Switch arm participants surveyed preferred long-acting therapy to their previous daily oral regimen (100%, n = 27/27). CONCLUSION: In this subgroup of ATLAS, 98% (n = 51/52) of participants at the Extension Phase W 96 analysis maintained virologic suppression with long-acting therapy. Safety, efficacy, and participant preference results support the therapeutic potential of long-acting CAB+RPV treatment for virologically suppressed people living with HIV-1

Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression

Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial

Objective: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. Methods: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors. Results: Of 211 treated patients, 73% (n = 155) had baseline viral load ⩾ 50 copies/mL and 27% (n = 56) had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%). Diarrhea was the most frequent adverse event (17%). Serious adverse events (no rash) occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC 12h was 5390 ng h/mL and C 0h was 353 ng/mL (N = 199). Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm) were 48% (74/155) (baseline viral load ⩾ 50 copies/mL) and 75% (42/56) (baseline viral load < 50 copies/mL). Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79) (non-adherent) versus 64% (44/69) (adherent subset). Conclusion: Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent) were similar to those previously observed for etravirine in HIV-1-infected adults. The relatively high level of non-adherence, also observed in the pharmacokinetic assessments, negatively impacted virologic response, especially in patients with ⩾50 copies/mL at baseline

Indoor tracking of multiple individuals with an 802.11ax Wi-Fi-based multi-antenna passive radar

We investigate indoor human multi-target tracking in cartesian coordinates based on range, Doppler and Angle-of-Arrival measurements obtained with a four-antenna passive bistatic radar capturing 802.11ax Wi-Fi signals. A reference antenna selection method is described to perform angle processing correctly when dealing with target detection diversity among antennas. The tracking is performed by an Unscented Kalman Filter (UKF) to handle the non-linear relation between the measurement space and the state space. A Joint Probabilistic Data Association Filter is coupled to the UKF to handle the data association between tracks and measurements when dealing with multiple targets. Simulations are performed to determine the tracking parameters under heavy constraints and identify key scenarios. An experimental setup is built using Universal Software Radio Peripherals, featuring an over-the-air phase calibration for angle processing with an anchor antenna. It is used to validate the proposed single and multi-target tracking scheme.info:eu-repo/semantics/publishe