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The proximity of two different materials leads to an intricate coupling of quasiparticles so that an unprecedented electronic state is often realized at the interface. Here, we demonstrate a resonance-type many-body ground state in graphene, a nonmagnetic two-dimensional Dirac semimetal, when grown on SmB6, a Kondo insulator, via thermal decomposition of fullerene molecules. This ground state is typically observed in three-dimensional magnetic materials with correlated electrons. Above the characteristic Kondo temperature of the substrate, the electron band structure of pristine graphene remains almost intact. As temperature decreases, however, the Dirac Fermions of graphene become hybridized with the Sm 4f states. Remarkable enhancement of the hybridization and Kondo resonance is observed with further cooling and increasing charge-carrier density of graphene, evidencing the Kondo screening of the Sm 4f local magnetic moment by the conduction electrons of graphene at the interface. These findings manifest the realization of the Kondo effect in graphene by the proximity of SmB6 that is tuned by the temperature and charge-carrier density of graphene.

When a clinical trial has a composite endpoint and a comparison of treatment strategies with multiple intervention components, interim data reviews by a data safety and monitoring board (DSMB) can be challenging as the data evolve on multiple fronts. We illustrate with a study in the treatment of Kaposi sarcoma (KS), an HIV-associated cancer with a multi-faceted disease presentation. The study, ACTG-A5264/AMC-067, was a 1:1 randomized trial to compare two strategies: immediate initiation of etoposide with antiretroviral therapy (ART), or ART with delayed etoposide upon disease progression. The outcome was a composite endpoint that included the following events, ordered from worst to best in the following three categories: (1) KS progression at 48 weeks, death, initiation of alternate KS treatment, loss to study follow-up; (2) stable KS; and (3) partial or complete KS response at 48 weeks. We present the interim results on the composite endpoint and the individual components, where components favored different study arms at an interim review. To facilitate interim data monitoring for complex trials, we recommend clear communications between the study team and the DSMB prior to the initiation of the trial on the need for a composite endpoint, the intentions behind the defined strategies, and relative importance of individual components of the composite endpoint. We also recommend flexibility in the timing of data reviews by the DSMB to interpret emerging data in multiple dimensions. Clinicaltrials.govNCT01352117.

The interplay between electron-electron interaction and electron-phonon coupling has been one of the key issues in graphene as it can provide information on the origin of enhanced electron-phonon coupling in graphene by foreign atoms. In ytterbium-decorated graphene on SiC substrate, electron-phonon coupling exhibits strong enhancement compared to that of as-grown graphene. Based on angle-resolved photoemission study, the presence of ytterbium is also found to result in the decrease of Fermi velocity, revealing the enhancement of electron-electron interaction within the Fermi liquid theory. Our finding on the concomitant enhancement of electron-electron interaction and electron-phonon coupling suggests a possibility of the interplay between the two representative many-body interactions in graphene decorated with foreign atoms.

BackgroundMild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART.MethodsChemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response.ResultsOf 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks.ConclusionsAmong HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low.Clinical trials registrationNCT01352117.

Background & aimsWe report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens.MethodsThe RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12 weeks of LDV/SOF or LDV/SOF + RBV. Compensated cirrhotic participants were randomized to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). Both studies used SVR at 12 weeks post-treatment (SVR12) as the primary endpoint.ResultsIn the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF + RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF + RBV for 12 weeks or LDV/SOF for 24 weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n = 1; GT1a n = 5) and all attained SVR12, with no serious AEs or premature discontinuations.ConclusionsIn this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved.

BackgroundWomen infected with human immunodeficiency virus (HIV) are disproportionately affected by human papillomavirus (HPV)-related anogenital disease, particularly with increased immunosuppression. AIDS Clinical Trials Group protocol A5240 was a trial of 319 HIV-infected women in the United States, Brazil, and South Africa to determine immunogenicity and safety of the quadrivalent HPV vaccine in 3 strata based on screening CD4 count: >350 (stratum A), 201-350 (stratum B), and ≤200 cells/µL (stratum C).MethodsSafety and serostatus of HPV types 6, 11, 16, and 18 were examined. HPV serological testing was performed using competitive Luminex immunoassay (HPV-4 cLIA). HPV type-specific seroconversion analysis was done for participants who were seronegative for the given type at baseline.ResultsMedian age of patients was 36 years; 11% were white, 56% black, and 31% Hispanic. Median CD4 count was 310 cells/µL, and 40% had undetectable HIV-1 load. No safety issues were identified. Seroconversion proportions among women at week 28 for HPV types 6, 11,16, and 18 were 96%, 98%, 99%, and 91%, respectively, for stratum A; 100%, 98%, 98%, and 85%, respectively, for stratum B, and 84%, 92%, 93%, and 75%, respectively, for stratum C.ConclusionsThe quadrivalent HPV vaccine targeted at types 6, 11, 16, and 18 was safe and immunogenic in HIV-infected women aged 13-45 years. Women with HIV RNA load >10 000 copies/mL and/or CD4 count

BackgroundWe hypothesized that nitazoxanide (NTZ) added to pegylated interferon alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C virus (HCV) virologic responses in HCV treatment-naïve HIV-1/HCV genotype 1 coinfected persons.MethodsProspective, single-arm study in which subjects received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG-IFN, and WBR. We compared the HCV virologic responses of these subjects to historical controls from the completed ACTG study A5178 who received PEG-IFN and WBR and had similar subject characteristics. Primary endpoints were early virologic response and complete early virologic response (EVR and cEVR).ResultsAmong 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8% (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the sustained virologic response (SVR) proportion was similar (27.3% in A5178; P = .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ was safe and well-tolerated.ConclusionWhereas EVR proportion improved significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls. NTZ may be associated with an attenuation of the effect of IL28B on HCV treatment response.