Clinical impact of double protease inhibitor boosting with Lopinavir/Ritonavir and Amprenavir as part of salvage antiretroviral therapy

Purpose: Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone. Method: Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician. Results: Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p = .12) or with time to virologic rebound (adjusted HR = 1.46, p = .34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p = .03). In a subset of 27 patients, the median LPV Ctrough was significantly lower in patients receiving APV (p = .04), and the median APV Ctrough was reduced compared to reported controls. Conclusion: Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings

Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Activation of herpes virus 6 (HHV6) has seen in Hodgkin's and non-Hodgkin's Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients.</p> <p>Methods</p> <p>Presence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBC's and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group.</p> <p>Results</p> <p>In a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBC's or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05).</p> <p>Conclusion</p> <p>The presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patients.</p

Prevalence of Elevated Blood Pressure and Association with Obesity in Egyptian School Adolescents

Aim. To investigate the relationship between high blood pressure (HBP) and obesity in Egyptian adolescents. Methods. A cross-sectional study of 1500 adolescents (11–19 years) in Alexandria, Egypt, was conducted. Resting BP was measured and measurements were categorized using the 2004 fourth report on blood pressure screening recommendations. Additional measures included height, weight, and waist and hip circumferences. Obesity was determined based on BMI, waist circumference (WC) and waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) indicators. Crude and adjusted odds ratios were used as measures of association between BP and obesity. Results. Prevalence rates of prehypertension and hypertension were 5.7% and 4.0%, respectively. Obesity was seen in 34.6%, 16.1%, 4.5%, and 16.7% according to BMI, WHR, WC, and WHtR, respectively. Adjusting for confounders, HBP was significantly associated with overall obesity based on BMI (OR = 2.18, 95%, CI = 1.38-3.44) and central obesity based on WC (OR = 3.14, 95%, CI = 1.67-5.94). Conclusion. Both overall obesity and central obesity were significant predictors of HBP in Egyptian adolescents

Imaging of Flow Patterns with Fluorescent Molecular Rotors

Molecular rotors are a group of fluorescent molecules that form twisted intramolecular charge transfer states (TICT) upon photoexcitation. Some classes of molecular rotors, among them those that are built on the benzylidene malononitrile motif, return to the ground state either by nonradiative intramolecular rotation or by fluorescence emission. In low-viscosity solvents, intramolecular rotation dominates, and the fluorescence quantum yield is low. Higher solvent viscosities reduce the intramolecular rotation rate, thus increasing the quantum yield. We recently described a different mechanism whereby the fluorescence quantum yield of the molecular rotor also depends on the shear stress of the solvent. In this study, we examined a possible application for shear-sensitive molecular rotors for imaging flow patterns in fluidic chambers. Flow chambers with different geometries were constructed from polycarbonate or acrylic. Solutions of molecular rotors in ethylene glycol were injected into the chamber under controlled flow rates. LED-induced fluorescence (LIF) images of the flow chambers were taken with a digital camera, and the intensity difference between flow and no-flow images was visualized and compared to computed fluid dynamics (CFD) simulations. Intensity differences were detectable with average flow rates as low as 0.1 mm/s, and an exponential association between flow rate and intensity increase was found. Furthermore, a good qualitative match to computed fluid dynamics simulations was seen. On the other hand, prolonged exposure to light reduced the emission intensity. With its high sensitivity and high spatial and temporal resolution, imaging of flow patterns with molecular rotors may become a useful tool in microfluidics, flow measurement, and control

Ultrafast electron dynamics and cubic optical nonlinearity of free standing thin film of double walled carbon nanotubes

Ultrafast degenerate pump-probe experiments performed on a free standing film of double walled carbon nanotubes near the first metallic transition energy of outer tube show ultrafast ($97 fs$) photobleaching followed by a photo-induced absorption with a slow relaxation of $1.8 ps$. Femtosecond closed and open aperture z-scan experiments carried out at the same excitation energy show saturation absorption and negative cubic nonlinearity. From these measurements, real and imaginary part of the third order nonlinear susceptibility are estimated to be Re($\chi^{(3)}) \sim -2.2 \times 10 ^{-9} esu$ and Im($\chi^{(3)}) \sim 1.1 \times 10 ^{-11} esu$.Comment: 8 pages, 3 figure

Expert consensus statement on the science of HIV in the context of criminal law

INTRODUCTION: Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.publishersversionpublishe

Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption

<p>Abstract</p> <p>Background</p> <p>The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.</p> <p>Results</p> <p>The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm³{Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.</p> <p>Conclusion</p> <p>The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.</p

Case Series of Fertility Treatment in HIV-Discordant Couples (Male Positive, Female Negative): The Ontario Experience

The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40 years from diagnosis) and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics). Participants identified a lack of information on the procedure (availability, safety). Sources of support (social networks, healthcare providers) were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and fertility service is significantly limited for this population and is accompanied with a number of challenges