Nearly 1 million people become infected every day with any of the four major curable sexually transmitted infections (STIs), namely trichomoniasis, chlamydia, gonorrhea, and syphilis. Despite huge ...global incidence, STIs remain as neglected diseases. The success of antiretrovirals for halting progression to AIDS in HIV-infected individuals and for stopping HIV transmission to uninfected contacts, either as pre- or post-exposure -prophylaxis, has to lead to increased risky sexual behaviors through risk compensation. Recent epidemics and outbreaks of STIs among men having sex with men reflect the global loss of fear to HIV/AIDS. The -alarming rising rates of STIs worldwide have been fueled by: (1) rapid spread of drug resistance, that is, for Neisseria gonorrhoeae and Mycoplasma genitalium; (2) unprecedented impact of recreational drugs (chemsex) and internet (apps, websites) for facilitating exposure to multiple sex partners; and (3) growing rates of sexual violence and commercial sex, associated with wars, refugees, migrations, traveling, and sexual tourism. Moreover, there is an increasing appreciation of sexual transmission for other agents, -including human T-lymphotropic virus type 1, hepatitis A and C viruses, Zika, and Ebola. For addressing this new scenario for STIs, an expert panel workshop was arranged in Madrid, Spain in May 2018. This review summarizes the discussions at the meeting.
Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are ...not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/10
CD4
T-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure.
To estimate life expectancy of people with HIV (PWH) and describe causes of death.
Antiretroviral therapy (ART)-naive adults from the CoRIS cohort starting ART in 2004-2019.
We calculated life ...expectancy at age 40 for men and women according to their ART initiation period, and stratified by transmission category, CD4 + cell count and AIDS diagnosis. We estimated life expectancy in 10-year age bands using life tables constructed from mortality rates, estimated through Poisson models.
Life expectancy increased from 65.8 95% confidence interval (CI) 65.0-66.6 in 2004-2008 to 72.9 (72.2-73.7) in 2014-2019 in men general population comparators (GPC): 79.1 and 81.2 years, respectively and from 65.8 (65.0-66.6) to 72.5 (71.8-73.3) in women (GPC: 84.9 and 86.4, respectively). Non-AIDS-related deaths accounted for 68% of deaths among men and 78% among women. Life expectancy was longer when starting ART with higher CD4 + cell counts and without AIDS. For men acquiring HIV through sex with men, starting ART in 2014-2019 without AIDS, life expectancy was 75.0 (74.2-75.7) with CD4 + cell count less than 200 cells/μl, rising to 78.1 (77.5-78.8) with CD4 + cell count at least 350 cells/μl. Corresponding figures were 70.1 (69.4-70.9) and 76.0 (75.3-76.7) for men acquiring HIV heterosexually (HTX) and 61.5 (60.7-62.3) and 69.0 (68.2-69.8) for those acquiring HIV through injection drug use (IDU). For women starting ART from 2014 without AIDS, life expectancy increased from 71.7 (71.0-72.4) to 77.3 (76.7-77.9) among HTX and from 63.7 (62.9-64.5) to 70.7 (70.0-71.5) among IDU.
Our findings confirm the progressive improvement of life expectancy in PWH in Spain over the last decades, supporting the insurability of PWH on suppressive ART in our current setting and time.
Marine reserves are widely used to protect species important for conservation and fisheries and to help maintain ecological processes that sustain their populations, including recruitment and ...dispersal. Achieving these goals requires well‐connected networks of marine reserves that maximize larval connectivity, thus allowing exchanges between populations and recolonization after local disturbances. However, global warming can disrupt connectivity by shortening potential dispersal pathways through changes in larval physiology. These changes can compromise the performance of marine reserve networks, thus requiring adjusting their design to account for ocean warming. To date, empirical approaches to marine prioritization have not considered larval connectivity as affected by global warming. Here, we develop a framework for designing marine reserve networks that integrates graph theory and changes in larval connectivity due to potential reductions in planktonic larval duration (PLD) associated with ocean warming, given current socioeconomic constraints. Using the Gulf of California as case study, we assess the benefits and costs of adjusting networks to account for connectivity, with and without ocean warming. We compare reserve networks designed to achieve representation of species and ecosystems with networks designed to also maximize connectivity under current and future ocean‐warming scenarios. Our results indicate that current larval connectivity could be reduced significantly under ocean warming because of shortened PLDs. Given the potential changes in connectivity, we show that our graph‐theoretical approach based on centrality (eigenvector and distance‐weighted fragmentation) of habitat patches can help design better‐connected marine reserve networks for the future with equivalent costs. We found that maintaining dispersal connectivity incidentally through representation‐only reserve design is unlikely, particularly in regions with strong asymmetric patterns of dispersal connectivity. Our results support previous studies suggesting that, given potential reductions in PLD due to ocean warming, future marine reserve networks would require more and/or larger reserves in closer proximity to maintain larval connectivity.
Global warming can disrupt ecological connectivity among marine reserves by shortening potential dispersal pathways through changes in larval physiology. These changes can compromise the effectiveness of marine reserve networks, thus requiring adjusting their design to account for ocean warming. Using the Gulf of California as case study, we propose a framework for planning marine reserve networks that integrates graph theory and changes in larval connectivity due to ocean warming. Given expected changes in larval connectivity, we show that our graph‐theoretical approach based on centrality of habitat patches can help design better connected marine reserve networks for the future with equivalent costs.
This study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation.
No consensus currently exists on the ...selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure.
After successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events.
Overall, 555 patients (mean age 75 ± 8 years, 63% male; median CHA2DS2-VASc congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category score 4 interquartile range (IQR): 3-6; median HAS-BLED hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol score 3 IQR: 2-4) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002).
After successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.
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OBJECTIVE:The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.
METHODS:HIV-infected, antiretroviral therapy–naive individuals in the ...HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8–9), or high (>9) CPE score. We estimated “intention-to-treat” hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.
RESULTS:A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58).
CONCLUSIONS:We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.
HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion ...that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by
intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of
and
genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (
= -0.8;
= 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.
There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.
The inclusion of nanostructures into cross-linked polymer networks allows obtaining nanocomposite hydrogels with suitable multifuncionalities for drug delivery applications. In this work, polypyrrole ...(PPy) nanoparticles, synthesized by a biocatalytic route, were encapsulated into a hydrogel matrix of poly(vinyl alcohol) (PVA) during its reticulation with glutaraldehyde. The novel composite hydrogels were characterized by infrared spectroscopy, thermogravimetric analysis, swelling kinetic measurements, scanning electron microscopy and cyclic voltammetry. The loading capabilities of PVA/PPy hydrogels were tested for metoprolol, a beta blocker used to treat angina, hypertension and to prevent heart attack. In vitro drug release profiles were obtained without and under electrical stimulations. The kinetics of drug release exhibited a power-law time dependence, typical of hydrogel-based systems. The application of electrical potentials changed the release rate of the drug, increasing or decreasing the delivery rate depending on bias voltage. Composite system of PVA and PPy combines the electrochemical redox properties of the conductive polymer with the swelling capacity and molecular diffusivity associated with PVA network; therefore, it can be considered a potential stimuli-responsive platform for biomedical applications.
Abstract
Background
The preventive effect that tenofovir/emtricitabine (FTC) could have against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human immunodeficiency virus-negative ...people is unknown. The objective of this study was to analyze the seroprevalence and clinical manifestations of COVID-19 among users of pre-exposure prophylaxis (PrEP), disoproxil fumarate/FTC (TDF/FTC), or tenofovir alafenamide (TAF)/FTC and to compare it to that of a control group.
Methods
An observational descriptive study of the seroprevalence of antibodies for SARS-CoV-2 among men who have sex with men and transgender women without use of PrEP (Group 1; n = 250) and PrEP users with TDF/FTC (n = 409) or TAF/FTC (n = 91) (Group 2; n = 500) was conducted from May11, 2020 to June 27, 2020. All participants were provided with a structured questionnaire that collected information on the variables to be analyzed, and testing for immunoglobulin G antibodies to SARS-CoV-2 (chemiluminescent microparticle immunoassay) was then carried out.
Results
The seroprevalence of SARS-CoV-2 was 9.2% (95% confidence interval CI, 5.9–13.5) in the group without PrEP and 15.0% (95% CI, 12.0–18.4) in the group with PrEP (P = .026). Among users of TDF/FTC it was 14.7% (95% CI, 11.4–18.5), and in users of TAF/FTC it was 16.5% (95% CI, 9.5–25.7) (P = .661). In those who tested positive for SARS-CoV-2 and receiving PrEP, 57.4% manifested symptoms, compared with 78.3% in the control group (P = .070). In users of TDF/FTC the figure was 53.3% and in users of TAF/FTC the figure was 73.3% (P = .100). The duration of symptoms was 11.5 days in the control group, 9.0 days in PrEP users (P = .116), 7.0 days in users of TDF/FTC, and 13.0 days in users of TAF/FTC (P = .100).
Conclusions
Users of PrEP, TDF/FTC, or TAF/FTC presented a higher seroprevalence to SARS-CoV-2 than the control group. No statistically significant differences were found in relation to clinical manifestations. The PrEP users should use the same prevention measures as those indicated for the general population.
Users of PrEP, TDF/FTC, or TAF/FTC, presented a higher seroprevalence to SARS-CoV-2 than the control group. No statistically significant differences were found in clinical manifestations. PrEP users should use the same prevention measures as those indicated for the general population.
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