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SummaryBackground This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle formulation of docetaxel. Methods The study was conducted in two parts. In part 1, dose-escalation using a standard 3 + 3 design was performed in two dosing schedules (every week (QW) and every 3 weeks (Q3W)). Part 2 was comprised of a dose expansion at 75 mg/m2 Q3W. PK studies were performed on both dosing schedules. Results Forty-two patients were recruited onto the study with a median age of 64(range 38–76); median number of prior systemic therapies was 5(range 0–10). Grade 3/4 treatment-related toxicities included: neutropenia (21.4 %), infusion related reaction (11.9 %), anemia (7.1 %), fatigue (4.8 %), diarrhea (4.8 %), and peripheral neuropathy (4.8 %). The maximum tolerated dose was 75 mg/m2 given on the Q3W schedule and was not determined on the QW schedule. In this heavily pre-treated population, four patients (12.9 %) achieved stable disease (SD) ≥ 4 months and 2 patients (6.5 %) achieved partial response (PR) for a clinical benefit rate (CBR) of 19.4 % (6/31 patients). The PRs were seen in prostate and breast adenocarcinoma (one each). CRLX301 exhibited some PK advantages over docetaxel including higher retention of drug in plasma, slower clearance and controlled slow release of docetaxel from the carrier. Conclusions In this heavily pretreated patient population, the safety profile was acceptable for CRLX301 therapy. There was some evidence of preliminary tumor efficacy, but further work is necessary to find the optimal dose and schedule of this formulation.Clinicaltrials.gov trial registration number: NCT02380677 (Date of registration: March 2, 2015).

People living with HIV-1 (PLWH) exhibit more rapid antibody decline following routine immunization and elevated baseline chronic inflammation than people without HIV-1 (PWOH), indicating potential for diminished humoral immunity during SARS-CoV-2 infection. Conflicting reports have emerged on the ability of PLWH to maintain humoral protection against SARS-CoV-2 coinfection during convalescence. It is unknown whether peak COVID-19 severity, along with HIV-1 infection status, associates with the quality and quantity of humoral immunity following recovery. Using a cross-sectional observational cohort from the United States and Peru, adults were enrolled 1-10 weeks after SARS-CoV-2 infection diagnosis or symptom resolution. Serum antibodies were analyzed for SARS-CoV-2-specific response rates, binding magnitudes, ACE2 receptor blocking, and antibody-dependent cellular phagocytosis. Overall, (a) PLWH exhibited a trend toward decreased magnitude of SARS-CoV-2-specific antibodies, despite modestly increased overall response rates when compared with PWOH; (b) PLWH recovered from symptomatic outpatient COVID-19 had comparatively diminished immune responses; and (c) PLWH lacked a corresponding increase in SARS-CoV-2 antibodies with increased COVID-19 severity when asymptomatic versus symptomatic outpatient disease was compared.

Background SARS-CoV-2 infection results in greater disease severity among immunocompromised individuals compared to healthy individuals. However, there is conflicting information about the impact of chronic HIV infection on immune responses to SARS-CoV-2 infection and vaccination. Method We used a combination of machine learning approaches and network analysis to explore 56 immune markers and comprehensively profile humoral and cellular immunity in a cross-sectional observational cohort of people without HIV (PWOH; n  = 216) and people living with HIV (PLWH; n  = 43) who recovered from SARS-CoV-2 infection (13–131 days since SARS-COV-2 diagnosis) early in the pandemic. Results PLWH recovered from symptomatic outpatient COVID-19 exhibit lower humoral and B cell responses to SARS-CoV-2 vs. PWOH but, surprisingly, both symptomatic outpatient and hospitalized PLWH have higher anti-endemic coronavirus antibody responses compared to PWOH counterparts and asymptomatic PLWH. The latter observation suggests that this was not strictly due to broadly elevated levels of anti-endemic coronavirus antibodies in PLWH. Moreover, correlation-based analysis reveals that while different compartments of the immune response to SARS-CoV-2 infection are positively correlated in PWOH recovered from symptomatic outpatient COVID-19, these correlations are weaker in PLWH. Conclusion Our analyses reveal significant differences in the coordinated immune responses elicited by infection in PLWH compared to PWOH. Plain language summary COVID-19 tends to be severe in individuals with underlying health conditions compared to those without. In particular, it is unclear whether individuals living with HIV exhibit immune responses to SARS-CoV-2 that differ from those without HIV. To investigate this gap, we use tools to analyze and compare immune responses to SARS-CoV-2 in individuals with and without HIV, who had recovered from the infection. Our study reveals that people living with HIV exhibit weaker immune responses to SARS-CoV-2 but stronger responses to endemic coronaviruses. Additionally, we observed that immune readouts measured in people living with HIV show weaker correlations with each other compared to those in individuals without HIV. These findings suggest that chronic, treated HIV infection may influence the immune response to SARS-CoV-2. Mielke et al. perform a multi-assay analysis of humoral and adaptive cellular responses to SARS-CoV-2 in people with HIV compared to people without HIV. Using supervised machine learning tools and network analysis, the authors find differences in the immune profile and anti-endemic coronavirus immune response between these two populations.