The use of preexposure treatments for HIV prophylaxis

Infection with human immunodeficiency virus remains a global concern with a significant number of incident infections still reported worldwide. The use of prophylaxis prior to exposure to the virus to prevent infection has been a growing area of recent research. Results in nonhuman primates and clinical trials in high-risk patient populations using preexposure prophylaxis have shown promising results in terms of efficacy and safety, especially relating to oral preexposure prophylaxis. The potential use of oral antiretroviral agents traditionally used for human immunodeficiency virus treatment as prophylaxis raises interesting considerations, such as the best agents available for such a role, long-term safety in healthy individuals, and the potential development of resistance to these agents should infection occur. From a public health perspective, the cost-effectiveness of implementing this preventive strategy has not been fully defined at this point in time

Clinical use of CCR5 inhibitors in HIV and beyond

Since the discovery of CCR5 as a coreceptor for HIV entry, there has been interest in blockade of the receptor for treatment and prevention of HIV infection. Although several CCR5 antagonists have been evaluated in clinical trials, only maraviroc has been approved for clinical use in the treatment of HIV-infected patients. The efficacy, safety and resistance profile of CCR5 antagonists with a focus on maraviroc are reviewed here along with their usage in special and emerging clinical situations. Despite being approved for use since 2007, the optimal use of maraviroc has yet to be well-defined in HIV and potentially in other diseases. Maraviroc and other CCR5 antagonists have the potential for use in a variety of other clinical situations such as the prevention of HIV transmission, intensification of HIV treatment and prevention of rejection in organ transplantation. The use of CCR5 antagonists may be potentiated by other agents such as rapamycin which downregulate CCR5 receptors thus decreasing CCR5 density. There may even be a role for their use in combination with other entry inhibitors. However, clinical use of CCR5 antagonists may have negative consequences in diseases such as West Nile and Tick-borne encephalitis virus infections. In summary, CCR5 antagonists have great therapeutic potential in the treatment and prevention of HIV as well as future use in novel situations such as organ transplantation. Their optimal use either alone or in combination with other agents will be defined by further investigation

Neutralizing anti-Tat antibodies prolonged HAART interruption in vaccines in a prospective structured interruption study

Anti-Tat therapeutic vaccination has been clinically investigated by different groups [1-4], given that 1) extracellular Tat protein induces T cell apoptosis and cellular immune suppression, 2) epidemiological data showed that LTNP exhibit high level of serum anti-Tat Ab, negatively correlated with p24 antigenemia, 3) in Tat immunized macaques, viremia decreased following SHIV challenge. Anti-Tat therapeutic vaccination using Tat Toxoid adjuvanted either with Seppic [1,2] or with alum or DcChol (Aventis Pasteur) proved to be safe. A prospective structured treatment interruption study (STI) monitored according to EU guidelines was conducted at Hospital St-Pierre, Brussels (Pr. N. Clumeck) on 31 vaccinees who received a DcChol adjuvanted Tat Toxoid (n = 12), a DcChol placebo (n = 8) or non adjuvanted Tat toxoid (n = 11). The 2 year study follow-up showed that vaccinees developing high titer of Abs neutralizing Tat bioactivity prolonged HAART-interruption.info:eu-repo/semantics/publishedOral presentation. From 2006 International Meeting of The Institute of Human VirologyBaltimore, USA. 17–21 November, 200

Suppression of non-adiabatic phases by a non-Markovian environment: easier observation of Berry phases

We consider a two-level system coupled to a highly non-Markovian environment when the coupling axis rotates with time. The environment may be quantum (for example a bosonic bath or a spin bath) or classical (such as classical noise). We show that an Anderson orthogonality catastrophe suppresses transitions, so that the system's instantaneous eigenstates (parallel and anti-parallel to the coupling axis) can adiabatically follow the rotation. These states thereby acquire Berry phases; geometric phases given by the area enclosed by the coupling axis. Unlike in earlier proposals for environment-induced Berry phases, here there is little decoherence, so one does not need a decoherence-free subspace. Indeed we show that this Berry phase should be much easier to observe than a conventional one, because it is not masked by either the dynamic phase or the leading non-adiabatic phase. The effects that we discuss should be observable in any qubit device where one can drive three parameters in the Hamiltonian with strong man-made noise.Comment: 14 pages - v4 Extended and improved presentation (complete change of method and results w.r.t. version 1

Self-Rated Health Predicts Healthcare Utilization in Heart Failure

BACKGROUND: Heart failure (HF) patients experience impaired functional status, diminished quality of life, high utilization of healthcare resources, and poor survival. Yet, the identification of patient-centered factors that influence prognosis is lacking. METHODS AND RESULTS: We determined the association of 2 measures of self-rated health with healthcare utilization and skilled nursing facility (SNF) admission in a community cohort of 417 HF patients prospectively enrolled between October 2007 and December 2010 from Olmsted County, MN. Patients completed a 12-item Short Form Health Survey (SF-12). Low self-reported physical functioning was defined as a score ≤ 25 on the SF-12 physical component. The first question of the SF-12 was used as a measure of self-rated general health. After 2 years, 1033 hospitalizations, 1407 emergency department (ED) visits, and 19,780 outpatient office visits were observed; 87 patients were admitted to a SNF. After adjustment for confounding factors, an increased risk of hospitalizations (1.52 [1.17 to 1.99]) and ED visits (1.48 [1.04 to 2.11]) was observed for those with low versus moderate-high self-reported physical functioning. Patients with poor and fair self-rated general health also experienced an increased risk of hospitalizations (poor: 1.73 [1.29 to 2.32]; fair: 1.46 [1.14 to 1.87]) and ED visits (poor: 1.73 [1.16 to 2.56]; fair: 1.48 [1.13 to 1.93]) compared with good-excellent self-rated general health. No association between self-reported physical functioning or self-rated general health with outpatient visits and SNF admission was observed. CONCLUSION: In community HF patients, self-reported measures of physical functioning predict hospitalizations and ED visits, indicating that these patient-reported measures may be useful in risk stratification and management in HF

Global gene expression of Prochlorococcus ecotypes in response to changes in nitrogen availability

Nitrogen (N) often limits biological productivity in the oceanic gyres where Prochlorococcus is the most abundant photosynthetic organism. The Prochlorococcus community is composed of strains, such as MED4 and MIT9313, that have different N utilization capabilities and that belong to ecotypes with different depth distributions. An interstrain comparison of how Prochlorococcus responds to changes in ambient nitrogen is thus central to understanding its ecology. We quantified changes in MED4 and MIT9313 global mRNA expression, chlorophyll fluorescence, and photosystem II photochemical efficiency (F(v)/F(m)) along a time series of increasing N starvation. In addition, the global expression of both strains growing in ammonium-replete medium was compared to expression during growth on alternative N sources. There were interstrain similarities in N regulation such as the activation of a putative NtcA regulon during N stress. There were also important differences between the strains such as in the expression patterns of carbon metabolism genes, suggesting that the two strains integrate N and C metabolism in fundamentally different ways

Efficient energy transfer in light-harvesting systems, I: optimal temperature, reorganization energy, and spatial-temporal correlations

Understanding the mechanisms of efficient and robust energy transfer in light-harvesting systems provides new insights for the optimal design of artificial systems. In this paper, we use the Fenna-Matthews-Olson (FMO) protein complex and phycocyanin 645 (PC 645) to explore the general dependence on physical parameters that help maximize the efficiency and maintain its stability. With the Haken-Strobl model, the maximal energy transfer efficiency (ETE) is achieved under an intermediate optimal value of dephasing rate. To avoid the infinite temperature assumption in the Haken-Strobl model and the failure of the Redfield equation in predicting the Forster rate behavior, we use the generalized Bloch-Redfield (GBR) equation approach to correctly describe dissipative exciton dynamics and find that maximal ETE can be achieved under various physical conditions, including temperature, reorganization energy, and spatial-temporal correlations in noise. We also identify regimes of reorganization energy where the ETE changes monotonically with temperature or spatial correlation and therefore cannot be optimized with respect to these two variables