Association of Cytomegalovirus DNA and Immunologic Markers of Cardiovascular Disease.

BackgroundPersons living with human immunodeficiency virus (HIV) (PLWH) with high cytomegalovirus (CMV)-specific interferon (IFN) γ response have increased numbers of endothelium homing receptor (CX3CR1)+-expressing cells that are associated with cardiovascular disease. The current study was performed to investigate the effect of cellular levels of CMV DNA on these markers.MethodsEighty paired peripheral blood mononuclear cell samples were collected ≥12 months apart from 40 CMV-seropositive PLWH with suppressed HIV RNA, who started antiretroviral therapy at median of 3-months of infection. The samples were assessed for CMV-specific IFN-γ response by means of enzyme-linked immunospot assay, and participants were classified as low responders (LRs) or high responders (HRs) based on IFN-γ production (≤100 or >100 spot-forming units [SFUs]/105 cells).ResultsOf the 40 participants, 26 (65%) were HRs and 14 (35%) LRs at baseline, which did not change over time or by CMV levels (median at first/second time points, 383/308 SFUs/106 cells for HRs vs 21/41 SFUs/106 for LRs). A decrease in IFN-γ over time was associated with higher CMV DNA levels (P < .01). High CMV response was also associated with increased CD28+CD27-CD4+ T cells expressing CX3CR1 (P < .001). Similarly, increased IFN-γ production was associated with increased CMV-specific CX3CR1+CD28+CD27-CD4+ and CD8+ T cells (P < .001).ConclusionsThese findings demonstrate that levels of CMV-specific IFN-γ response in PLWH are stable over time, and that HRs have increased circulating T cells expressing CX3CR1 that may put them at increased risk of cardiovascular disease and other inflammatory diseases

Willingness to Participate in HIV Research at the End of Life (EOL)

Introduction Animal models have been vital for scientific discovery but have limitations, especially in infectious disease research. It is essential to develop a means to study these diseases in human models. We hypothesized that altruistic people would willingly participate in research near the end-of-life (EOL), for the benefit of science and to provide one last gift to society. Methodology Two surveys were administered to 377 self-reported HIV-negative and 96 HIV-positive individuals. Hypothetical questions assessed their willingness to participate in altruistic research in the last 6 months of life, which might result in a shortened lifespan or physical discomforts. The self-reported HIV-negative group was also asked about willingness to be exposed to infectious pathogens for the sake of research. Results Almost all responders expressed willingness to participate in research at the EOL, regardless of HIV-status. The majority of participants were willing to endure physical discomfort for the sake of research. ‘Blood draws’ was identified as the most tolerable physical discomfort (>70% in both groups). In both groups, >60% were willing to shorten their lifespans for the sake of research. A third of the self-reported HIV-negative group expressed willingness to be exposed to at least one infectious agent to participate in EOL research. Conclusions Our exploratory study demonstrates that people would welcome the opportunity to participate in altruistic research near the EOL. Such research could greatly impact the way infectious disease research is conducted. This study is limited however by its hypothetical nature. Further research is necessary to confirm this interest in those with terminal illness before any further clinical research effort at the EOL can be performed

Using UAVs and Photogrammetry in Bathymetric Surveys in Shallow Waters

Indexado en ScopusThe use of UAV (unmanned aerial vehicle) platforms and photogrammetry in bathymetric surveys has been established as a technological advancement that allows these activities to be conducted safely, more affordably, and at higher accuracy levels. This study evaluates the error levels obtained in photogrammetric UAV flights, with measurements obtained in surveys carried out in a controlled water body (pool) at different depths. We assessed the relationship between turbidity and luminosity factors and how this might affect the calculation of bathymetric survey errors using photogrammetry at different shallow-water depths. The results revealed that the highest luminosity generated the lowest error up to a depth of 0.97 m. Furthermore, after assessing the variations in turbidity, the following two situations were observed: (1) at shallower depths (not exceeding 0.49 m), increased turbidity levels positively contributed error reduction; and (2) at greater depths (exceeding 0.49 m), increased turbidity resulted in increased errors. In conclusion, UAV-based photogrammetry can be applied, within a known margin of error, in bathymetric surveys on underwater surfaces in shallow waters not exceeding a depth of 1 m.Revisión por pare

Estimating the Timing of Mother-to-Child Transmission of the Human Immunodeficiency Virus Type 1 Using a Viral Molecular Evolution Model

Background: Mother-to-child transmission (MTCT) is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT. Materials and Methods Six-hundred and twenty-two clonal env sequences from the RNA and DNA viral population were longitudinally sampled from nine HIV-1 infected mother-and-child pairs [range: 277–1034 days]. For each transmission pair, timing of MTCT was determined using a coalescent-based model within a Bayesian statistical framework. Results were compared with available estimates of MTCT timing obtained with the classic biomedical approach based on serial HIV DNA detection by PCR assays. Results: Four children were infected during pregnancy, whereas the remaining five children were infected at time of delivery. For eight out of nine pairs, results were consistent with the transmission periods assessed by standard PCR-based assay. The discordance in the remaining case was likely confused by co-infection, with simultaneous introduction of multiple maternal viral variants at the time of delivery. Conclusions: The study provided the opportunity to validate the Bayesian coalescent approach that determines the timing of MTCT of HIV-1. It illustrates the power of population genetics approaches to reliably estimate the timing of transmission events and deepens our knowledge about the dynamics of viral evolution in HIV-infected children, accounting for the complexity of multiple transmission events

Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Diversity and Tropism in 145 Patients With Primary HIV-1 Infection

Viral diversity during primary HIV-1 infection (PHI) relating to transmission mode, HIV-1 subtypes, and viral tropism was revisited. Varying mucosal barriers were not associated with differences in diversities of founder populations. CXCR4-using viruses are present during PHI but remain exceptional case

Outbreaks of Pneumocystis Pneumonia in 2 Renal Transplant Centers Linked to a Single Strain of Pneumocystis: Implications for Transmission and Virulence

By restriction fragment length polymorphism analysis, 2 outbreaks of Pneumocystis pneumonia in renal transplant patients in Europe were shown to be caused by the same strain of Pneumocystis; another outbreak in Japan was caused by a different strai

Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption.

BACKGROUND: Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated. METHODS: The evolution of plasma HIV-RNA (432 measurements) and cell-associated HIV-DNA (325 measurements) after cessation of cART (median exposure 18 months) was described for 33 participants from the Zurich Primary HIV Infection Study using linear regression and compared with 545 measurements from 79 untreated controls with clinically diagnosed primary HIV infection, respectively a known date for seroconversion. RESULTS: On average, early treated individuals were followed for 37 months (median) after cART cessation; controls had 34 months of pre-cART follow-up. HIV-RNA levels one year after cART interruption were −0.8 log(10) copies/mL [95% confidence interval −1.2;−0.4] lower in early treated patients compared with controls, but this difference was no longer statistically significant by year three of follow-up (−0.3 [−0.9; 0.3]). Mean HIV-DNA levels rebounded from 2 log(10) copies [1.8; 2.3] on cART to a stable plateau of 2.7 log(10) copies [2.5; 3.0] attained 1 year after therapy stop, which was not significantly different from cross-sectional measurements of 9 untreated members of the control group (2.8 log(10) copies [2.5; 3.1]). CONCLUSIONS: The rebound dynamics of viral markers after therapy cessation suggest that early cART may indeed limit reservoir size of latently infected cells, but that much of the initial benefits are only transient. Owing to the non-randomized study design the observed treatment effects must be interpreted with caution

A Community-Driven Framework to Prioritize the Use of Donated Human Biological Materials in the Context of HIV Cure-Related Research at the End of Life

Initiated in 2017 after extensive community engagement, the Last Gift program enrolls altruistic volunteers willing to donate their cells and tissues at the end of life to allow studies on HIV reservoir dynamics across anatomical sites. As the Last Gift team received tissue requests outside the scope of HIV cure research, we noticed the absence of guiding frameworks to help prioritize the use of altruistically donated human biological materials. In this commentary, we present a proposed framework for prioritizing the use of donated human biological materials within and outside the end-of-life (EOL) HIV cure research context, using the Last Gift study as an example. First, we discuss regulatory and policy considerations, and highlight key ethical values to guide prioritization decisions. Second, we present our prioritization framework and share some of our experiences prioritizing requests for donated human biological materials within and outside EOL HIV cure research.