Formulation preference, tolerability and quality of life assessment following a switch from lopinavir/ritonavir soft gel capsule to tablet in human immunodeficiency virus-infected patients

<p>Abstract</p> <p>Background</p> <p>Lopinavir/ritonavir (LPV/r) tablet compared to the soft gel capsule (SGC) formulation has no oleic acid or sorbitol, has no refrigeration or food-restriction requirements, and has less pharmacokinetic variability. We compared the tolerability, quality of life (QoL), and formulation preference after switching from LPV/r SGC to the tablet formulation.</p> <p>Methods</p> <p>In a prospective, single-arm, cohort study-design, 74 human immunodeficiency virus (HIV) infected subjects stable on LPV/r-based therapy were enrolled prior to (n = 25) or 8 weeks (n = 49) after switching from SGC to tablet. Baseline data included clinical laboratory tests, bowel habit survey (BHS) and QoL questionnaire (recalled if enrolled post-switch). Global Condition Improvement (GCI)-score, BHS-score, QoL-score, and formulation preference data were captured at weeks 4 and 12.</p> <p>Results</p> <p>At week 12 post-enrollment; the tablet was preferred to the SGC (74% vs. 10%, p < 0.0001). GCI-overall-tolerability score was 2.46 ± 3.30 on a scale of -7 to +7, with 90% admitting to feeling better or about the same. Stool frequency, consistency, volume, and ± blood improved, however the improvement was significant in "consistency" only (p = 0.03). Aggregate Bowel Habit-Profile improved (BHS-score change = -0.227, p = 0.01). Inverse relationship existed between GCI and BHS (slope = -1.2, p = 0.02) at week-4, suggesting that improved overall-tolerability was related to better gastrointestinal (GI)-tolerance. QoL-scores were stable. Mean reductions in total cholesterol of 9.20 mg/dL (p = 0.02), in triglycerides of 33 mg/dL (p = 0.04), and in HDL of 4.50 mg/dL (p = 0.01) unrelated to lipid-lowering therapy, were observed at week 12.</p> <p>Conclusions</p> <p>LPV/r-tablet was well tolerated and preferred to the SGC in HIV infected subjects, with stable QoL and appreciable improvement in GI-tolerability. The unexpected changes in lipid profile deserve further evaluation.</p

Significant improvements in self-reported gastrointestinal tolerability, quality of life, patient satisfaction, and adherence with lopinavir/ritonavir tablet formulation compared with soft gel capsules

<p>Abstract</p> <p>Background</p> <p>The tablet formulation of ritonavir-boosted lopinavir (LPV/r; Kaletra^®) has many advantages over the soft gel capsule (SGC) formulation, including lower pill count, no refrigeration requirement, and no dietary restrictions. These advantages may help improve patient compliance and therefore increase adherence to treatment. However, there are limited data regarding patient preferences and only recently was the comparative efficacy and tolerability data of LPV/r SGC versus tablet formulation presented at an international conference. To address this deficit, we conducted a market research survey to assess potential tolerability benefits, patient satisfaction, changes in adherence, and formulation preference in patients switching from SGCs to the tablet formulation. Data from 332 patients who switched from LPV/r SGCs twice-daily (BID) to tablets BID and 41 patients who switched from LPV/r SGCs BID or once daily (QD) to tablets QD were analyzed.</p> <p>Results</p> <p>Switching from SGCs to a tablet formulation of LPV/r was associated with increased patient satisfaction, tolerability and self-reported adherence to treatment; gastrointestinal side effects were reduced. In addition, respondents indicated that they preferred the tablet formulation to the SGC.</p> <p>Conclusion</p> <p>The LPV/r tablet formulation provides HIV-infected patients with multiple benefits over the SGC in terms of tolerability and convenience. Additional assessments to further define the tolerability profile of the LPV/r tablet, including studies using once-daily dosing, are warranted.</p

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV : results of a 96‐week, phase 3b, open‐label, switch trial in virologically suppressed people ≥65 years of age

Objectives Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study. Methods In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged >= 65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96. Results Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA >= 50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0-98.1) and 74.4% (64/86; 95% CI 63.9-83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR -2.3, 2.0). Median self-reported adherence was 100% (IQR 100-100%). Conclusions Switching to B/F/TAF is an effective long-term option for virologically suppressed adults >= 65 years of age, with favourable safety and tolerability profiles in this population