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PURPOSE: Whilst significant progress has been made to defeat HIV infection, the efficacy of antiretroviral (ARV) therapy in the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectable nanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user. To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA and CAB LA via self-disabling dissolving microarray patches (MAPs). METHODS: Dissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, with various nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robust and were capable of penetrating ex vivo skin with intradermal ARV deposition. RESULTS: In a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profiles, with therapeutically relevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study, repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout the duration of the study. CONCLUSIONS: These results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPV and CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one that is capable of being painlessly administered in the comfort of the patient's own home on a biweekly or less frequent basis.
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Fármacos Anti-HIV , Infecções por HIV , Ratos , Animais , Rilpivirina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Antirretrovirais , PiridonasRESUMO
Shanghai is one of the largest cities in China and has the highest proportion of inbound travelers in the world. The HIV (human immunodeficiency virus) infection status of this population can reflect the global HIV epidemic trend to a certain extent. Therefore, we conducted a retrospective epidemic survey to clarify the prevalence and characteristics of HIV-1 infection among inbound travelers applying for Shanghai residency. The retrospective cohort analysis included a total of 50,830 inbound tourists/travelers who applied for Shanghai residency from 2005 to 2016. HIV-1 infection rates were determined based on HIV-1 antibody testing. Among all the recruited inbound travelers, 245 were HIV-1 positive, with an infection rate of 0.48%. The detection rate of HIV in males was significantly higher than in females (χ2 = 62.584, P < 0.0001). Those aged 18-30 years, 31-40 years, and >40 years accounted for 34.3%, 39.6%, and 26.1% of the infected population, respectively. Although the annual detection rates were different, the trend analysis results showed no increase in HIV-1 prevalence rates among the sampling years (Cochran-Armitage Z = 2.543, P = 0.111). Proportions of individuals infected through homosexual transmission increased over the study period (Cochran-Armitage Z = 5.41, P < 0.001), while the proportion infected through heterosexual declined over time (Cochran-Armitage Z = 3.38, P = 0.001). The rate and characteristics of HIV-1 infection among foreign applicants for residency in Shanghai were identified in the study. The results provide the necessary epidemiological data for monitoring the HIV-1 epidemic among international entry travelers and contribute to establishing relevant policies and regulations for HIV control and prevention.
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Globally more than a million sexually transmitted infections occur daily, and over 53 000 [47,000-60,000] women aged 15 and over were living with human immunodeficiency virus / acquired immunodeficiency syndrome in Pakistan by the year 2020. This situation becomes graver when the sexually transmitted infections exist as co-infections while remaining undiagnosed or under-diagnosed. Additionally, herpetic or papillomavirus lesions are more recurrent, more extensive and have more serious consequences in human immunodeficiency virus-positive patients. Literature shows a dramatic increase in morbidity and mortality due to the occurrence of malignancies in genital co-infections. There is a key concern that every single adolescent female living in Pakistan is at a high risk of acquiring viral sexually transmitted infections along with malignancy of the cervix. As such, the health and future of this age group is already imperilled. Needless to mention that the practice of routine cervical screening and diagnostic laboratory services offered to a common woman in Pakistan have been less than satisfactory for decades. Therefore, to meet the minimum expectations regarding the Millennium Development Goals for sexual and reproductive health and rights 2030, it has now become imperative for the health sector to develop and implement scientific and community-based policies for comprehensive and multidisciplinary diagnostic strategies leading to early and effective management of viral sexually transmitted infections and subsequent neoplasia.
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Coinfecção , Infecções por HIV , Infecções Sexualmente Transmissíveis , Neoplasias do Colo do Útero , Viroses , Adolescente , Detecção Precoce de Câncer , Feminino , Genitália Feminina , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Viroses/epidemiologiaRESUMO
We provide here a general view on the interactions of surfactants with viruses, with a particular emphasis on how such interactions can be controlled and employed for inhibiting the infectivity of enveloped viruses, including coronaviruses. The aim is to provide to interested scientists from different fields, including chemistry, physics, biochemistry, and medicine, an overview of the basic properties of surfactants and (corona)viruses, which are relevant to understanding the interactions between the two. Various types of interactions between surfactant and virus are important, and they act on different components of a virus such as the lipid envelope, membrane (envelope) proteins and nucleocapsid proteins. Accordingly, this cannot be a detailed account of all relevant aspects but instead a summary that bridges between the different disciplines. We describe concepts and cover a selection of the relevant literature as an incentive for diving deeper into the relevant material. Our focus is on more recent developments around the COVID-19 pandemic caused by SARS-CoV-2, applications of surfactants against the virus, and on the potential future use of surfactants for pandemic relief. We also cover the most important aspects of the historical development of using surfactants in combatting virus infections. We conclude that surfactants are already playing very important roles in various directions of defence against viruses, either directly, as in disinfection, or as carrier components of drug delivery systems for prophylaxis or treatment. By designing tailor-made surfactants, and consequently, advanced formulations, one can expect more and more effective use of surfactants, either directly as antiviral compounds or as part of more complex formulations.
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This review reports the recent advances in surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) platforms for the diagnosis of infectious diseases. As observed through the recent infection outbreaks of COVID-19 worldwide, a timely diagnosis of the disease is critical for preventing the spread of a disease and to ensure epidemic preparedness. In this regard, an innovative point-of-care diagnostic method is essential. Recently, SERS-based assay platforms have received increasing attention in medical communities owing to their high sensitivity and multiplex detection capability. In contrast, LFAs provide a user-friendly and easily accessible sensing platform. Thus, the combination of LFAs with a SERS detection system provides a new diagnostic modality for accurate and rapid diagnoses of infectious diseases. In this context, we briefly discuss the recent application of LFA platforms for the POC diagnosis of SARS-CoV-2. Thereafter, we focus on the recent advances in SERS-based LFA platforms for the early diagnosis of infectious diseases and their applicability for the rapid diagnosis of SARS-CoV-2. Finally, the key issues that need to be addressed to accelerate the clinical translation of SERS-based LFA platforms from the research laboratory to the bedside are discussed.
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OBJECTIVE: To estimate the probability of human immunodeficiency virus (HIV)-1 transmission from different key HIV population groups using probabilistic modelling. METHODS: This study was conducted in December 2020. A probabilistic model was used to estimate the probability of HIV-1 transmission from different key HIV population groups in Larkana. Our model was run on three probabilistic assumptions: 1) each replication gave two conceivable results: 'true' or 'false'; 2) the chance of giving a 'true' result is the same for each replication; and 3) the replications are independent - 'true' in one will not impact the likelihood of 'true' in another. RESULTS: The results estimated the probability of HIV transmission in key HIV population groups in Larkana to range between 0.42-0.54 per trial, where the highest probability of transmission was predicted for men who have sex with men (MSM; 0.54 per trial), followed by transgender (TG; 0.46 per trial) and people who inject drugs (PWID; 0.457 per trial). CONCLUSIONS: Our results suggest that there is a high likelihood of HIV transmission by key population groups in Larkana, such as MSM, TG, and PWID. Mathematic models, such as one proposed in our study can aid the HIV and acquired immunodeficiency syndrome (AIDS) control programmes in evaluating and optimising the strategies in controlling transmission of HIV from the key population groups.
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Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Paquistão/epidemiologia , Grupos PopulacionaisRESUMO
PURPOSE: To assess the efficacy and safety of topical application of clotrimazole versus others in the treatment of oropharyngeal candidiasis (OPC). METHOD: Four electronic databases, registries of ongoing trials, and manual search were used to identify randomized controlled trials (RCTs) that compared the efficacy of clotrimazole to other antifungal agents in patients who were clinically diagnosed with oral candidiasis up to November 1st, 2019. Primary outcomes were clinical response and mycological cure rates. Secondary outcomes include relapse rate, incidence of systemic infections, and compliance. Adverse effects were also evaluated. RESULTS: Sixteen RCTs with a total of 1685 patients were included. Half of the eligible studies were considered at high risk of performance bias and more than a third, at high risk of reporting bias. Our analysis showed no significant difference in clinical response between clotrimazole and all other antifungal agents. However, clotrimazole was less effective in terms of mycologic cure and relapse rate. Sensitivity analysis comparing clotrimazole to other topical antifungal agents only showed no differences in clinical response, microbiologic cure or relapse. Further sensitivity analysis showed significant efficacy of fluconazole over clotrimazole. CONCLUSION: This meta-analysis indicated that clotrimazole is less effective than fluconazole but as effective as other topical therapies in treating OPC. Well-designed high-quality RCT is needed to validate these findings.
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BACKGROUND: There are approximately 72,000 people living with HIV/AIDS (PLHIV) in Peru. Non-adherence to antiretroviral therapy (ART) is the most important factor for therapeutic failure and the development of resistance. Peru has achieved moderate progress in meeting the 90-90-90 targets, but only 60% of PLHIV receiving ART are virally suppressed. The purpose of this study was to understand ART adherence in the Peruvian context, including developing sociodemographic and clinical profiles, evaluating the clinical management strategies, and analyzing the relationships between the variables and adherence of PLHIV managed at a regional HIV clinic in Lambayeque Province (Northern Peru). METHODS: This was a cross-sectional study with 180 PLHIV adults, non-randomly but consecutively selected with self-reported ART compliance (78.2% of the eligible population). The PLHIV profile (PLHIV-Pro) and the Simplified Medication Adherence Questionnaire (SMAQ) were used to collect sociodemographic information, clinical variables, and data specific to ART adherence. Descriptive analysis of sociodemographic and clinical characteristics was performed. Bivariate analysis was performed with the Mann-Whitney test, Chi square test, and Yates correction. RESULTS: The 180 PLHIV sample included 78.9% men, 49.4% heterosexual, 45% with a detectable HIV-1 viral load less than 40 copies/ml, 58.3% not consistently adherent, and only 26.1% receiving Tenofovir + Lamivudine + Efavirenz. Risk factors significant for non-adherence included concurrent tuberculosis, discomfort with the ART regime, and previous pauses in ART. Multivariate analysis of nested models indicated having children is a protector factor for adherence. CONCLUSIONS: Self-reported adherence appeared to be low and the use of first-line therapy is not being prescribed homogeneously. Factors associated with nonadherence are both medical and behavioral, such as having tuberculosis, pausing ART, or experiencing discomfort with ART. The Peruvian government needs to update national technical standards, monitor medication availability, and provide education to health care professionals in alignment with evidence-based guidelines and international recommendations. Instruments to measure adherence need to be developed and evaluated for use in Latin America.
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Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , HIV/efeitos dos fármacos , Humanos , Masculino , Peru , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
In the last 30â¯years, since the discovery that vanadium is a cofactor found in certain enzymes of tunicates and possibly in mammals, different vanadium-based drugs have been developed targeting to treat different pathologies. So far, the in vitro studies of the insulin mimetic, antitumor and antiparasitic activity of certain compounds of vanadium have resulted in a great boom of its inorganic and bioinorganic chemistry. Chemical speciation studies of vanadium with amino acids under controlled conditions or, even in blood plasma, are essential for the understanding of the biotransformation of e.g. vanadium antidiabetic complexes at the physiological level, providing clues of their mechanism of action. The present article carries out a bibliographical research emphaticizing the chemical speciation of the vanadium with different amino acids and reviewing also some other important aspects such as its chemistry and therapeutical applications of several vanadium complexes.
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To investigate the epidemiological features and risk factors of HBV, HCV, and syphilis infection among HIV-infected patients in West China Hospital. A retrospective study was conducted with HIV-infected patients from 2014 to 2016 in West China hospital, SCU. Serum makers for HBV, HCV, and syphilis were detected. Among 894 HIV-infected patients, the prevalence of HIV/HBV, HIV/HCV, HIV/syphilis co-infections was 14.4%, 5.7%, and 18.9% respectively. HIV/HBV/HCV, HIV/HCV/syphilis, and HIV/HBV/syphilis triple co-infection was 7 (0.7%), 12(1.3%), 29(3.2%) respectively. The rate of effective vaccination against HBV was only 7.7% in HIV-infected patients. Age (OR = 0.243 95% CI: 0.114 -0.518), ethnicity (OR = 3.654 95% CI: 1.849-7.218) and education level (OR = 0.140 95% CI: 0.033-0.606) are risk factors affecting HIV/HCV co-infection. A high prevalence of HIV/syphilis, HIV/HBV, and HIV/ HCV co-infection can be observed in west China. The rate for HIV-infected patients who were effectively vaccinated against HBV was fewer than 10%.
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Coinfecção , Infecções por HIV/complicações , Vacinas contra Hepatite B/imunologia , Hepatite B/complicações , Hepatite C/complicações , Sífilis/complicações , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , China/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite C/sangue , Hepatite C/epidemiologia , Hepatite C/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Sífilis/sangue , Sífilis/epidemiologia , Sífilis/imunologia , Vacinação , Adulto JovemRESUMO
STUDY QUESTION: How do semen parameters of HIV-infected men under antiretroviral treatment compare with WHO parameters of normal semen, and what factors are associated with any differences? SUMMARY ANSWER: Semen quality in most HIV-infected patients under antiretroviral treatment exceeds WHO limits, but the number falling below them is higher than would be expected in a healthy population. Exposure to efavirenz has a significant association with dysmotility. WHAT IS KNOWN ALREADY: Dysmotility is the most frequently described sperm alteration related to HIV infection, and it has recently been linked to treatment with non-nucleoside reverse transcriptase inhibitors, particularly to efavirenz. STUDY DESIGN, SIZE, DURATION: Prospective cohort study. Between March 2002 and December 2013, 139 HIV-infected men undergoing antiretroviral therapy were enrolled. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were male members of serodiscordant couples who attended a clinic for sexually transmitted infections (STIs) in Madrid and requested reproductive counselling. Sociodemographic, behavioural and clinical data were collected. CD4+ lymphocyte count, HIV viral load, serology/viral load of hepatitis B and C viruses, syphilis serology and other STIs diagnosis were performed. Semen parameters were assessed through standard sperm analysis and were compared with WHO 2010 reference values. Factors associated with impaired semen parameters were evaluated by bivariate and multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The median values of all assessed semen parameters were within a normal range, but in up to 19% of HIV-positive males, at least one parameter of semen quality was below the normal range. A significant association between treatment with efavirenz and the presence of dysmotility was detected in the multivariate analysis. LIMITATIONS, REASONS FOR CAUTION: Our results cannot demonstrate a causal relationship between exposure to efavirenz and impaired motility. We do not have a real comparison group as the WHO cohort is international and may not reflect local variations in semen characteristics. Subjects who requested reproductive counselling might not be representative of HIV-positive men in general. WIDER IMPLICATIONS OF THE FINDINGS: Since efavirenz is still widely used in current therapeutic regimens may be affecting fertility in seropositive men who desire procreation. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. The authors have no conflict of interest to declare.
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Antirretrovirais/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Adulto , Alcinos , Antirretrovirais/farmacologia , Benzoxazinas/farmacologia , Ciclopropanos , Humanos , Masculino , Estudos Prospectivos , Análise do Sêmen , Contagem de Espermatozoides , Carga ViralRESUMO
Peptide based-vaccines are becoming one of the most widely investigated prophylactic and therapeutic health care interventions against a variety of diseases, including cancer. However, the lack of a safe and highly efficient adjuvant (immune stimulant) is regarded as the biggest obstacle to vaccine development. The incorporation of a peptide antigen in a nanostructure-based delivery system was recently shown to overcome this obstacle. Nanostructures are often formed from antigens conjugated to molecules such as polymers, lipids, and peptide, with the help of self-assembly phenomenon. This review describes the application of self-assembly process for the production of peptide-based vaccine candidates and the ability of these nanostructures to stimulate humoral and cellular immune responses.
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STUDY QUESTION: Are antiretroviral therapies associated with semen alterations in HIV-infected men? SUMMARY ANSWER: Antiretroviral regimens that included the non-nucleosidic reverse transcriptase inhibitor efavirenz were associated with a significant impairment of sperm motility, whereas regimens without efavirenz were not associated with significant semen changes. WHAT IS KNOWN ALREADY: Semen alterations including decreased ejaculate volume and sperm motility have been reported in HIV-infected men. The hypothesis ascribing reduced sperm motility to damages induced in sperm mitochondria by nucleosidic (or nucleotidic) reverse transcriptase inhibitors (NRTIs) has not been confirmed in HIV-infected patients and the effects of antiretroviral treatments on semen parameters remain unclear. STUDY DESIGN, SIZE, DURATION: This case-control study compared semen characteristics across 378 HIV-1 infected patients receiving different antiretroviral regimens or never treated by antiretroviral drugs, in whom an initial semen analysis was done between 2001 and 2007. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients were partners from serodiscordant couples requesting medical assistance to procreate safely. Their status with regard to antiretroviral therapy at the time of semen analysis was categorized as follows: 1/ never treated patients (n = 66); 2/ patients receiving NRTIs only (n = 49); 3/ patients receiving a NRTIs + protease inhibitor (PI) regimen (n = 144); 4/ patients receiving a NRTIs + non-nucleosidic reverse transcriptase inhibitor (NNRTI) regimen (n = 119). Semen parameters were assessed through standard semen analysis. Additional analyses included measurement of sperm motion parameters using computer-assisted semen analysis, seminal bacteriological analysis, seminal biochemical markers and testosterone plasmatic levels. All analyses were performed in the Cochin academic hospital. The data were analyzed through multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm motility was the only semen parameter which significantly varied according to treatment status. The median percentage of rapid spermatozoa was 5% in the group of patients receiving a regimen including efavirenz versus 20% in the other groups (P < 0.0001). Accordingly, sperm velocity was reduced by about 30% in this group (P < 0.0001). The role of chance was minimized by the strict definition and the size of the study population, which included a large enough group of never treated patients, the controlled conditions of semen collection and analysis, the multivariate analysis, the specificity and the high significance level of the observed differences. LIMITATIONS, REASONS FOR CAUTION: The design of the study did not allow demonstrating a causal link between exposure to efavirenz and sperm motility. WIDER IMPLICATIONS OF THE FINDINGS: As efavirenz is widely used in current antiretroviral therapy, these findings may concern many HIV-infected men wishing to have children. This justifies further assessment of the consequences on fertility of the exposure to efavirenz. Moreover, the possibility of common cellular impacts underlying adverse effects of efavirenz in sperm cells and neurons deserved investigation. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. None of the authors has any conflict of interest to declare.
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Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infertilidade Masculina/induzido quimicamente , Inibidores da Transcriptase Reversa/efeitos adversos , Motilidade dos Espermatozoides/efeitos dos fármacos , Adulto , Alcinos , Benzoxazinas/farmacologia , Benzoxazinas/uso terapêutico , Estudos de Casos e Controles , Ciclopropanos , Infecções por HIV/fisiopatologia , Humanos , Infertilidade Masculina/fisiopatologia , Masculino , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Análise do SêmenRESUMO
International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of ART remains poor. Qualitative social research within HIV-positive communities is urgently needed to capture people's lived experiences and may address some of this deficit in understanding.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Adesão à Medicação/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Atitude do Pessoal de Saúde , Austrália , Canadá , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Necessidades e Demandas de Serviços de Saúde , Humanos , Programas de Rastreamento/estatística & dados numéricos , Adesão à Medicação/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autoeficácia , Apoio Social , Fatores Socioeconômicos , Reino UnidoRESUMO
Several proteins and RNAs expressed by mammalian viruses have been reported to interfere with RNA interference (RNAi) activity. We investigated the ability of the HIV-1-encoded RNA elements Trans-Activation Response (TAR) and Rev-Response Element (RRE) to alter RNAi. MicroRNA let7-based assays showed that RRE is a potent suppressor of RNAi activity, while TAR displayed moderate RNAi suppression. We demonstrate that RRE binds to TAR-RNA Binding Protein (TRBP), an essential component of the RNA Induced Silencing Complex (RISC). The binding of TAR and RRE to TRBP displaces small interfering (si)RNAs from binding to TRBP. Several stem-deleted RRE mutants lost their ability to suppress RNAi activity, which correlated with a reduced ability to compete with siRNA-TRBP binding. A lentiviral vector expressing TAR and RRE restricted RNAi, but RNAi was restored when Rev or GagPol were coexpressed. Adenoviruses are restricted by RNAi and encode their own suppressors of RNAi, the Virus-Associated (VA) RNA elements. RRE enhanced the replication of wild-type and VA-deficient adenovirus. Our work describes RRE as a novel suppressor of RNAi that acts by competing with siRNAs rather than by disrupting the RISC. This function is masked in lentiviral vectors co-expressed with viral proteins and thus will not affect their use in gene therapy. The potent RNAi suppressive effects of RRE identified in this study could be used to enhance the expression of RNAi restricted viruses used in oncolysis such as adenoviruses.
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Genes env , Repetição Terminal Longa de HIV , HIV-1/genética , Interferência de RNA , Proteínas de Ligação a RNA/genética , Adenoviridae/genética , Adenoviridae/metabolismo , Ligação Competitiva , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Células HEK293 , HIV-1/metabolismo , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Células Jurkat , Lentivirus/genética , Lentivirus/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Conformação de Ácido Nucleico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Complexo de Inativação Induzido por RNA/genética , Complexo de Inativação Induzido por RNA/metabolismo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/metabolismoRESUMO
BACKGROUND: Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women. STUDY DESIGN: Retrospective cohort analysis. SETTING & PARTICIPANTS: Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years. PREDICTOR: The primary predictor was serum albumin concentration. OUTCOMES: We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR). MEASUREMENTS: Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression. RESULTS: After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001). LIMITATIONS: The cohort is composed of only female participants from urban communities within the United States. CONCLUSIONS: Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria.
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Nefropatia Associada a AIDS , Insuficiência Renal Crônica , Albumina Sérica/análise , Nefropatia Associada a AIDS/sangue , Nefropatia Associada a AIDS/epidemiologia , Nefropatia Associada a AIDS/fisiopatologia , Adulto , Creatinina/sangue , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , HIV , Humanos , Testes de Função Renal , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Selection of an antiretroviral regimen for people living with HIV (PLWH) involves various clinical considerations, such as comorbidities, archived drug resistance mutations, concomitant medications, and potential drug interactions and side effects. Alterations in the surface area and pH of the gastrointestinal tract following bariatric surgery may alter absorption, antiretroviral pharmacokinetics and viral suppression. Data on the efficacy of antiretroviral (ARV) therapy in PLWH who have undergone bariatric surgery are limited or lacking for new antiretrovirals, such as dolutegravir and bictegravir. METHODS: This case series reports virologic outcomes and side effects in eight cases of PLWH receiving ARV therapy who underwent bariatric surgery. A systematic literature review was performed to review the available literature on the efficacy and safety of antiretroviral regimens in PLWH who have undergone bariatric surgery. RESULTS: Virologic suppression was not impacted for obese PLWH who underwent bariatric surgery following failure of life-style modifications and pharmacological therapy. CONCLUSIONS: There were no deleterious effects on HIV progression for PLWH that underwent bariatric surgery. More prospective research is required to validate the effects of bariatric surgery on immunologic and virologic function outcomes. Close involvement of HIV and surgical specialists is recommended to manage ARV therapy in patients undergoing bariatric surgery.
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Fármacos Anti-HIV , Cirurgia Bariátrica , Infecções por HIV , HIV-1 , Humanos , Fármacos Anti-HIV/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , HIV-1/fisiologia , Estudos ProspectivosRESUMO
Human papillomavirus (HPV) is a common sexually transmitted infection with wide-ranging clinical manifestations. High-risk anogenital HPV genotypes have also been reported to cause extragenital disease. We describe the case of a 69-year-old male patient living with HIV who was diagnosed with HPV-16 associated Bowen's Disease (BD) of the right middle finger nailbed, despite good virologic control and immune reconstitution. The lesion was managed surgically with adjunctive post-exposure HPV vaccination. This case adds to the growing body of evidence of extra-genital HPV disease attributable to anogenital genotypes in people living with HIV.
Assuntos
Doença de Bowen , Infecções por HIV , Infecções por Papillomavirus , Humanos , Masculino , Doença de Bowen/virologia , Doença de Bowen/cirurgia , Idoso , Infecções por HIV/complicações , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Neoplasias Cutâneas/virologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 16/genéticaRESUMO
Background: In countries with limited resources, including Ethiopia, HIV is diagnosed using a rapid serological test, which does not detect the infection during the window period. Pregnant women who test negative for HIV on the first test may seroconvert throughout pregnancy. Women who are seroconverted during pregnancy may not have received interventions, as they are considered HIV-negative unless they are retested for HIV at the end of their pregnancy. Due to limited data on HIV seroconversion, this study aimed to measure the extent of HIV seroconversion and to identify associated factors among seronegative pregnant women attending ANC in Ethiopia. Methods: Institution-based cross-sectional study was conducted among HIV-negative pregnant women attending the ANC in Ethiopia between June and July 2020. Socio-demographic, clinical, and behavioral data were collected through face-to-face questionnaires and participants' records review. HIV retesting was performed to determine the current HIV status of pregnant women. The data collected were entered into Epi data version 4.4.1 and were exported and analyzed by SPSS version 25. A p-value < 0.25 in the bivariate analysis was entered into multivariable logistic regression analysis and a p-value of < 0.05 was considered statistically significant. Result: Of the 494 pregnant women who tested negative for HIV on their first ANC test, six (1.2%) tested positive on repeat testing. Upon multivariable logistic regression, pregnant women who have had a reported history of sexually transmitted infections [AOR = 7.98; 95% CI (1.21, 52.82)], participants' partners reported travel history for work frequently [AOR = 6.00; 95% CI (1.09, 32.99)], and sexually abused pregnant women [AOR = 7.82; 95% CI (1.194, 51.24)] were significantly associated with HIV seroconversion. Conclusion: The seroconversion rate in this study indicates that pregnant women who are HIV-negative in early pregnancy are at an ongoing risk of seroconversion throughout their pregnancy. Thus, this study highlights the benefit of a repeat HIV testing strategy in late pregnancy, particularly when the risk of seroconversion or new infection cannot be convincingly excluded. Therefore, repeated testing of HIV-negative pregnant women in late pregnancy provides an opportunity to detect seroconverted pregnant women to enable the timely use of ART to prevent mother-to-child transmission of HIV infection.
RESUMO
BACKGROUND: Adherence to medication and retention in care are key contributors to the efficacy of pre-exposure prophylaxis (PrEP) for prevention of HIV. Therefore, it is important to understand factors that may impact retention in various settings that prescribe PrEP. METHODS: We evaluated factors associated with retention in care 3 and 12 months after PrEP initiation at a primary care HIV clinic in San Diego. Retention was defined as having an office/virtual visit within 1 month from the 3- or 12-months time point or interacting with the clinic leading to medication being refilled. RESULTS: A total of 199 patients were included. Retention rates were 74.4% and 52.8% at 3 and 12 months respectively. In the multivariate analysis, reporting depression or anxiety was associated with being retained in care (p = 0.004) and identifying as cisgender female was associated with lack of retention (p = 0.04) at 3 months. Testing positive for a sexually transmitted infection was associated with 12-months retention (p = 0.004); however, this was likely influenced by difference in the frequency of testing in those retained versus not retained. CONCLUSION: Ongoing efforts to determine the optimal method for provision of PrEP care that supports retention for different populations at risk for HIV, are needed.