Predictors of Virologic Failure in HIV/AIDS Patients Treated with Highly Active Antiretroviral Therapy in Brasília, Brazil During 2002–2008

Little data exists concerning the efficacy of the antiretroviral therapy in the Federal District in Brazil, therefore in order to improve HIV/AIDS patients’ therapy and to pinpoint hot spots in the treatment, this research work was conducted. Of 139 HIV/AIDS patients submitted to the highly active antiretroviral therapy, 12.2% failed virologically. The significant associated factors related to unresponsiveness to the lentiviral treatment were: patients’ place of origin (OR = 3.28; IC95% = 1.0–9.73; P = 0.032) and Mycobacterium tuberculosis infection (RR = 2.90; IC95% = 1.19–7.02; P = 0.019). In the logistic regression analysis, the remaining variables in the model were: patients’ birthplace (OR = 3.28; IC95% = 1.10–9.73; P = 0.032) and tuberculosis comorbidity (OR = 3.82; IC95% = 1.19–12.22; P = 0.024). The patients enrolled in this survey had an 88.0% therapeutic success rate for the maximum period of one year of treatment, predicting that T CD4+ low values and elevated viral loads at pretreatment should be particularly considered in tuberculosis coinfection, besides the availability of new antiretroviral drugs displaying optimal activity both in viral suppression and immunological reconstitution

Topical Issues for Particle Acceleration Mechanisms in Astrophysical Shocks

Particle acceleration at plasma shocks appears to be ubiquitous in the universe, spanning systems in the heliosphere, supernova remnants, and relativistic jets in distant active galaxies and gamma-ray bursts. This review addresses some of the key issues for shock acceleration theory that require resolution in order to propel our understanding of particle energization in astrophysical environments. These include magnetic field amplification in shock ramps, the non-linear hydrodynamic interplay between thermal ions and their extremely energetic counterparts possessing ultrarelativistic energies, and the ability to inject and accelerate electrons in both non-relativistic and relativistic shocks. Recent observational developments that impact these issues are summarized. While these topics are currently being probed by astrophysicists using numerical simulations, they are also ripe for investigation in laboratory experiments, which potentially can provide valuable insights into the physics of cosmic shocks.Comment: 13 pages, no figures. Invited review, accepted for publication in Astrophysics and Space Science, as part of the HEDLA 2006 conference proceeding

Fermi acceleration in astrophysical jets

We consider the acceleration of energetic particles by Fermi processes (i.e., diffusive shock acceleration, second order Fermi acceleration, and gradual shear acceleration) in relativistic astrophysical jets, with particular attention given to recent progress in the field of viscous shear acceleration. We analyze the associated acceleration timescales and the resulting particle distributions, and discuss the relevance of these processes for the acceleration of charged particles in the jets of AGNs, GRBs and microquasars, showing that multi-component powerlaw-type particle distributions are likely to occur.Comment: 6 pages, one figure; based on talk at "The multimessenger approach to unidentified gamma-ray sources", Barcelona/Spain, July 2006; accepted for publication in Astrophysics and Space Scienc

Host range, transmissibility and antigenicity of a pangolin coronavirus

The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration approved drugs, and neutralized by COVID-19 patient sera and SARS-CoV-2 therapeutic antibodies in vitro. A pan-Sarbecovirus antibody and SARS-CoV-2 S2P recombinant protein vaccine protected BALB/c mice from PgCoV infection. In K18-hACE2 mice, PgCoV infection caused severe clinical disease, but mice were protected by a SARS-CoV-2 human antibody. Efficient PgCoV replication in primary human cells and hACE2 mice, coupled with a capacity for airborne spread, highlights an emergence potential. However, low competitive fitness, pre-immune humans and the benefit of COVID-19 countermeasures should impede its ability to spread globally in human populations

High Energy Processes in Pulsar Wind Nebulae

Young pulsars produce relativistic winds which interact with matter ejected during the supernova explosion and the surrounding interstellar gas. Particles are accelerated to very high energies somewhere in the pulsar winds or at the shocks produced in collisions of the winds with the surrounding medium. As a result of interactions of relativistic leptons with the magnetic field and low energy radiation (of synchrotron origin, thermal, or microwave background), the non-thermal radiation is produced with the lowest possible energies up to $\sim$100 TeV. The high energy (TeV) gamma-ray emission has been originally observed from the Crab Nebula and recently from several other objects. Recent observations by the HESS Cherenkov telescopes allow to study for the first time morphology of the sources of high energy emission, showing unexpected spectral features. They might be also interpreted as due to acceleration of hadrons. However, theory of particle acceleration in the PWNe and models for production of radiation are still at their early stage of development since it becomes clear that realistic modeling of these objects should include their time evolution and three-dimensional geometry. In this paper we concentrate on the attempts to create a model for the high energy processes inside the PWNe which includes existence not only relativistic leptons but also hadrons inside the nebula. Such model should also take into account evolution of the nebula in time. Possible high energy expectations based on such a model are discussed in the context of new observations.Comment: 9 pages, 1 figure, Proc. Multimessenger approach to high energy gamma-ray source

Virologic outcomes in early antiretroviral treatment: HPTN 052

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results from the HIV Prevention Trials Network 052 Trial

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts

HIV Drug Resistance in Adults Receiving Early vs. Delayed Antiretroviral Therapy: HPTN 052

Introduction: We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm 3 (early ART arm) or 1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure. Results: HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure. Conclusions: In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load