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1.
Magn Reson Imaging ; 95: 27-38, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36265696

RESUMEN

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head "receive" and a quadrature body "transmit" coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.


Asunto(s)
Infecciones por VIH , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/tratamiento farmacológico
2.
J Surg Res ; 281: 338-344, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35945037

RESUMEN

INTRODUCTION: Examining burden of diseases could shed light on priorities of public health interventions and research funding. This study examined trends of the U.S. top leading causes of death from 1981 to 2019 using the total number of deaths, age-adjusted death rate, and years of potential life lost (YPLLs). METHODS: Data were from the Web-based Injury Statistics Query and Reporting System. This study gathered total number of deaths, age-adjusted death rates per 100,000 people, and YPLLs under 70 y of age (YPLL-70) from 1981 to 2019 for the top 10 leading causes of death and human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) for each year. The 39 y from 1981 to 2019 were evenly divided into three study periods: 1981-1993, 1994-2006, and 2007-2019. The percent change of YPLL-70 over three time periods for the top ten leading causes of death and AIDS was calculated. Trends of age-adjusted death rates and YPLL-70 of the top five leading causes of death based on the 2018-2019 death data were also reported by graphing them against time from 1981 to 2019 to highlight major mortality causes. Age-adjusted death rates for the top five leading causes of deaths and the National Institutes of Health (NIH) annual funding level in 2019 were graphed together to illustrate funding discrepancy in injury research and prevention. RESULTS: The total number of deaths caused by malignant neoplasms in 2019 was 244,994, followed by 183,442 deaths of heart diseases, 121,476 deaths of unintentional injuries, and 41,051 suicide deaths. Despite an initial -22.20% drop of YPPL-70 during 1981-1993, unintentional injuries experienced significant increases of 19.38% and 18.59% of YPLL-70 in 1994-2006 and 2007-2019, respectively. The age-adjusted death rate for unintentional injuries was 1182 per 100,000 people in 2019, and the NIH funding in the same year was $897 million. In comparison, the age-adjusted death rate for cancer, heart disease, and human immunodeficiency virus/AIDS was 786, 649, and 30 per 100,000 people while the NIH funding was $2,560, $2,394, and $3037 million, respectively. CONCLUSIONS: Unintentional injuries, suicide, and homicide were consistently among the top leading causes of death and YPLL-70, so they should be prioritized in public health planning, research, and federal funding allocation. Injury and trauma research is severely underfunded by the U.S. premier funding agency.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Cardiopatías , Heridas y Lesiones , Estados Unidos/epidemiología , Humanos , Causas de Muerte , Homicidio , Causalidad , Infecciones por VIH/epidemiología , Esperanza de Vida
3.
Neuroimaging Clin N Am ; 33(1): 147-165, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36404041

RESUMEN

Human immunodeficiency virus (HIV) infection causes substantial morbidity and mortality worldwide. Although antiretroviral therapy (ART) has changed the epidemiology of HIV in the last 20 years with increased survival and decreasing incidence of opportunistic infections (OI), CNS OI remain a major cause of morbidity. Improved survival has also increased neurological presentations due to co morbid conditions, treatment related side effects and inflammatory syndromes. Being familiar with the imaging findings, the impact of ART and interpretation of imaging in the context of clinical and laboratory findings is important for radiologists as well as clinicians in the management of HIV-infected patients.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA , Infecciones por VIH , Humanos , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico por imagen , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/tratamiento farmacológico , VIH
4.
Int J Cancer ; 152(2): 183-194, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36054877

RESUMEN

South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995-2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case-control associations between specific cancers and HIV, using participants with non-infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (ORadj ; 95%CI): (99.1;72.6-135.1), non-Hodgkin lymphoma (11.3;9.3-13.6), cervical cancer (2.7;2.4-3.0), Hodgkin lymphoma (3.1;2.4-4.2), cancer of the eye/conjunctiva (18.7;10.1-34.7), anogenital cancers (anus [2.1;1.4-3.2], penis [5.4;2.7-10.5], vulva [4.8;3.5-6.4], vagina [5.5;3.0-10.2]), oropharyngeal cancer (1.6;1.3-1.9), squamous cell carcinoma of the skin (3.5;2.4-4.9), melanoma (2.0;1.2-3.5) and cancer of the larynx (1.7;1.3-2.4). Kaposi's sarcoma odds ratios increased from the pre-ART (1995-2004) to the early ART (2005-2009) period but declined in the late ART (2010-2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV-associated cancers found in other African settings. The odds ratios of conjunctival and HPV-related cancers continue to rise in the ART era as the HIV positive population ages.


Asunto(s)
Infecciones por VIH , Sarcoma de Kaposi , Neoplasias del Cuello Uterino , Humanos , Femenino , Masculino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Sudáfrica/epidemiología , Sarcoma de Kaposi/epidemiología , Negros , Antirretrovirales
5.
Behav Brain Res ; 437: 114109, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36108778

RESUMEN

Human immunodeficiency virus (HIV) continues to infect millions worldwide, negatively impacting neurobehavioral function. Further understanding of the combined effects of HIV and methamphetamine use is crucial, as methamphetamine use is prevalent in people with HIV. The HIV-associated protein Tat may contribute to cognitive dysfunction, modeled preclinically in mice using doxycycline (DOX)-inducible Tat expression (iTat). Tat may exert its effects on cognitive function via disruption of the dopamine transporter, similar to the action of methamphetamine. Additionally, Tat and methamphetamine both decrease interneuron populations, including those expressing calbindin. It is important to understand the combined effects of Tat and methamphetamine in preclinical models of HIV infection. Here, we used iTat transgenic mice and a chronic binge regimen of methamphetamine exposure to determine their combined impact on reward learning and motivation. We also measured calbindin expression in behavior-relevant brain regions. Before induction with DOX, iTat mice exhibited no differences in behavior. Chronic methamphetamine exposure before Tat induction impaired initial reward learning but did not affect motivation. Furthermore, DOX-induced Tat expression did not alter behavior, but slowed latencies to retrieve rewards. This effect of Tat, however, was not observed in methamphetamine-treated mice, indicative of a potential protective effect. Finally, Tat expression was associated with an increase in calbindin-expressing cells in the VTA, while methamphetamine exposure did not alter calbindin numbers. These findings may indicate a protective role of methamphetamine in HIV neuropathology, which in turn may help in our understanding of why people with HIV use methamphetamine at disproportionately higher rates.


Asunto(s)
Trastornos Relacionados con Anfetaminas , Infecciones por VIH , Metanfetamina , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Animales , Humanos , Ratones , Calbindinas/metabolismo , Modelos Animales de Enfermedad , Infecciones por VIH/complicaciones , Infecciones por VIH/psicología , Metanfetamina/efectos adversos , Metanfetamina/farmacología , Ratones Transgénicos , Recompensa , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Trastornos Relacionados con Anfetaminas/complicaciones , Trastornos Relacionados con Anfetaminas/metabolismo
6.
J Infect Chemother ; 29(1): 109-111, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36116718

RESUMEN

Long-acting therapy of cabotegravir and rilpivirine is expected to free people from the negative emotions of living with HIV associated with taking drugs, but problems such as increased number of hospital visits, lack of anti-HBV activity, and limited convenience in people with concomitant drugs have been noted. In this single-center, prospective, cross-sectional study, we investigated background factors of people living with HIV in Japan who chose cabotegravir plus rilpivirine. Forty-seven percent (36 of 76) of individuals chose this regimen, but many people living with HIV who visited the hospital once every 3 months or needed concomitant medications due to complications chose this regimen and there were no significant differences in background factors that could affect convenience between the groups of those who switched and those who did not.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Rilpivirina/uso terapéutico , Proyectos Piloto , Estudios Transversales , Japón , Estudios Prospectivos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico
7.
J Virol Methods ; 311: 114647, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36343742

RESUMEN

Accurate HIV and CD4 testing are critical in program implementation, with HIV misdiagnosis having serious consequences at both the client and/or community level. We implemented a comprehensive training and Quality Assurance (QA) program to ensure accuracy of point-of-care HIV and CD4 count testing by lay counsellors during the Botswana Combination Prevention Project (BCPP). We compared the performance of field testing by lay counsellors to results from an accredited laboratory to ascertain accuracy of testing. All trained lay counsellors passed competency assessments and performed satisfactorily in proficiency testing panel evaluations in 2013, 2014, and 2015. There was excellent agreement (99.6 %) between field and laboratory-based HIV test results; of the 3002 samples tested, 960 and 2030 were concordantly positive and negative respectively, with 12 misclassifications (kappa score 0.99, p < 0.0001). Of the 149 HIV-positive samples enumerated for CD4 count in the field using PIMA at a threshold of ≤ 350 cells/µl; there was 86 % agreement with laboratory testing, with only 21 misclassified. The mean difference between field and lab CD4 testing was - 16.16 cells/µl (95 % CI -5.4 to 26.9). Overall, there was excellent agreement between field and laboratory results for both HIV rapid test and PIMA CD4 results. A standard training package to train lay counsellors to accurately perform HIV and CD4 point-of-care testing in field settings was feasible, with point-of-care results obtained by lay counsellors comparable to laboratory-based testing.


Asunto(s)
Infecciones por VIH , Sistemas de Atención de Punto , Humanos , Botswana , Yoduro de Potasio , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Recuento de Linfocito CD4 , Personal de Salud
8.
J Interpers Violence ; 38(1-2): NP1920-NP1949, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35510547

RESUMEN

Economic hardship is a driver of entry into sex work, which is associated with high HIV risk. Yet, little is known about economic abuse in women employed by sex work (WESW) and its relationship to uptake of HIV prevention and financial support services. This study used cross-sectional baseline data from a multisite, longitudinal clinical trial that tests the efficacy of adding economic empowerment to traditional HIV risk reduction education on HIV incidence in 542 WESW. Mixed effects logistic and linear regressions were used to examine associations in reported economic abuse by demographic characteristics, sexual behaviors, HIV care-seeking, and financial care-seeking. Mean age was 31.4 years. Most WESW were unmarried (74%) and had less than primary school education (64%). 48% had savings, and 72% had debt. 93% reported at least one economic abuse incident. Common incidents included being forced to ask for money (80%), having financial information kept from them (61%), and being forced to disclose how money was spent (56%). WESW also reported partners/relatives spending money needed for bills (45%), not paying bills (38%), threatening them to quit their job(s) (38%), and using physical violence when earning income (24%). Married/partnered WESW (OR = 2.68, 95% CI:1.60-4.48), those with debt (OR = 1.70, 95% CI:1.04-2.77), and those with sex-work bosses (OR = 1.90, 95% CI:1.07-3.38) had higher economic abuse. Condomless sex (ß = +4.43, p < .05) was higher among WESW experiencing economic abuse, who also had lower odds of initiating PrEP (OR = .39, 95% CI:.17-.89). WESW experiencing economic abuse were also more likely to ask for cash among relatives (OR = 2.36, 95% CI:1.13-4.94) or banks (OR = 2.12, 95% CI:1.11-4.03). The high prevalence of HIV and economic abuse in WESW underscores the importance of integrating financial empowerment in HIV risk reduction interventions for WESW, including education about economic abuse and strategies to address it. Programs focusing on violence against women should also consider economic barriers to accessing HIV prevention services.


Asunto(s)
Infecciones por VIH , Trabajo Sexual , Femenino , Humanos , Adulto , Estudios Transversales , Uganda , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Apoyo Financiero
9.
J Interpers Violence ; 38(1-2): NP443-NP465, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35343294

RESUMEN

Intimate partner violence (IPV) is associated with a higher risk of contracting HIV and developing worse HIV outcomes. This cross-sectional, mixed methods study presents data on IPV using the Conflicts Tactics Scale (CTS2-S) among 180 persons with HIV in Lima, Peru, as well as qualitative interviews with 7 of them and 18 of their community caregivers. This study used data collected for a randomized controlled trial (RCT), CASAommunity Based Accompaniment with Supervised Antiretrovirals (CASA) Community-based Accompaniment with Supervised Antiretrovirals (CASA). Physical or sexual IPV was self-reported in 82 (45.6%) of participants reporting having been in a relationship in the last year and 59,8% of those were involved in bidirectional violence. Coping subscales, social support, and stigma were associated with IPV. Intimate partner violence negatively impacted patient adherence to medication and care, particularly during times of severe conflict. In conclusion, profound psychosocial vulnerability-including low social support, substance use as coping, and HIV stigma-contextualize IPV among people with HIV. Bidirectional violence often evolved over time as victims negotiated inter-personal strategies for survival, including retaliation. Interventions should focus on a deeper understanding IPV and facilitating of coping mechanisms to help people with HIV stay in care.


Asunto(s)
Infecciones por VIH , Violencia de Pareja , Humanos , Estudios Transversales , Perú/epidemiología , Violencia de Pareja/psicología , Conducta Sexual , Infecciones por VIH/psicología , Parejas Sexuales/psicología , Prevalencia
10.
J Interpers Violence ; 38(1-2): NP37-NP59, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35365046

RESUMEN

National prevalence of physical and sexual violence and its relationship to sexual behaviors are unknown among men who have sex with men (MSM). We estimated 12-month prevalence of physical and sexual violence and assessed relationships between violence and sexual behaviors among MSM. Data were obtained from National HIV Behavioral Surveillance 2017 that used time-space sampling methods to recruit and interview MSM in 22 U.S. cities. Weighted percentages with 95% confidence intervals (CI) were reported. Adjusted prevalence ratios (aPR) and 95% CIs were calculated using logistic regression with predicted marginal means. Overall, 10.2% (95% CI: 9.3%-11.2%) of MSM experienced physical violence only, 3.2% (95% CI: 2.7%-3.7%) experienced sexual violence only, and 2.3% (95% CI: 1.9%-2.7%) experienced both types of violence, in the past 12 months. Compared to MSM who did not experience violence, those who did reported higher percentages of unemployment, poverty, homelessness, same-sex discrimination, non-injection drug use, and binge drinking. Violence was not independently associated with condomless anal sex among MSM. MSM who experienced both types of violence were more likely than those who did not experience violence to have had four or more male sex partners (aPR=1.18, 95% CI: 1.02-1.37). MSM who experienced both types of violence (aPR=2.49, 95% CI: 1.52-4.09), sexual violence (aPR=2.27, 95% CI: 1.47-3.52), or physical violence (aPR=1.76, 95% CI: 1.27-2.44) were more likely than those who did not experience violence to have had exchange sex. Recent physical violence and sexual violence are common among MSM. Findings highlight the importance of violence screening and suggest the need for tailored interventions that improve the safety and economic security of MSM who experience violence, including those who exchange sex.


Asunto(s)
Infecciones por VIH , Delitos Sexuales , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Ciudades/epidemiología , Asunción de Riesgos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Conducta Sexual , Prevalencia
11.
Int J Cancer ; 152(2): 249-258, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35852007

RESUMEN

We are reporting (a) updated incidence of cervical intraepithelial neoplasia (CIN) among women who did not have colposcopic or histopathological disease at baseline and (b) disease outcomes among women treated for CIN and their follow-up HPV status; in a cohort of women living with HIV (WHIV). The median overall follow-up was 3.5 years (IQR 2.8-4.3). The incidence of any CIN and that of CIN 2 or worse disease was 16.7 and 7.0 per 1000 person-years of observation (PYO), respectively. Compared with women who were HPV negative at baseline, women who cleared HPV infection had 23.95 times increased risk of incident CIN 2 or worse lesions (95% CI 2.40-661.07). Women with persistent HPV infection had 138.18 times increased risk of CIN 2 or worse lesions (95% CI 20.30-3300.22). Complete disease regression was observed in 65.6% of the HPV positive women with high-grade CIN and were treated with thermal ablation but HPV persistence was seen in 44.8% of those with high-grade disease. Among those who did not have any disease at baseline and were also HPV negative, about 87% (95% CI 83.79-89.48) women remained HPV negative during consecutive HPV test/s with the median interval of 3.5 years. Long-term surveillance of WHIV treated for any CIN is necessary for the prevention of cervical cancer among them. Our study provides an early indication that the currently recommended screening interval of 3 to 5 years among WHIV may be extended to at least 5 years among HPV negative women. Increasing the screening interval can be cost saving and improve scalability among WHIV to support WHO's cervical cancer elimination initiative.


Asunto(s)
Neoplasia Intraepitelial Cervical , Infecciones por VIH , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Detección Precoz del Cáncer/efectos adversos , Papillomaviridae , Estudios de Cohortes , India/epidemiología , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiología , Neoplasia Intraepitelial Cervical/patología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología
12.
Methods Mol Biol ; 2552: 399-408, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36346605

RESUMEN

Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth" of a given antibody, an essential aspect of antibody design.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Anticuerpos Anti-VIH/genética , Anticuerpos Neutralizantes , Epítopos
13.
Sci Total Environ ; 857(Pt 2): 159410, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36257445

RESUMEN

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has been a worrisome public health problem in the world. However, evidence for associations between short-term exposure to particulate matter (PM) and mortality among HIV/AIDS patients is scarce. METHODS: We collected daily death records in people with HIV/AIDS from all counties (N = 103) of Hubei province, China from 2018 to 2019. The county-level daily concentrations of PM1, PM2.5 and PM10 in the same period were extracted from ChinaHighAirPollutants dataset. A time-stratified case-crossover design with conditional logistic regression analysis was performed to assess the associations between PM and mortality. RESULTS: Each 1 µg/m3 increased in PM1 corresponded with 0.89 % elevated in all-cause deaths (ACD) at lag 0-4 days. The largest effects of PM1, PM2.5 and PM10 on AIDS-related deaths (ARD) were detected at lag 0-4 days, and PM1 [percent changes in odds ratio: 2.51 % (95 % CIs: 0.82, 4.22)] appeared greater health hazards than PM2.5 [1.24 % (95 % CIs: 0.33, 2.15)] as well as PM10 [0.65 % (95 % CIs: 0.01, 1.30)]. In subgroup analyses, the significant associations of PM1/PM2.5 and ACD were only found in male and the cold season. We also observed the effects of PM1 and PM10 on ARD were significantly stronger (P for interaction <0.05) in males than females. In addition, we caught sight of HIV/AIDS patients aged over 60 years old were more susceptible to ARD caused by PM than younger population. CONCLUSIONS: Our study suggested PM1 was positively linked with the risk of ACD and ARD. Male patients with HIV/AIDS were more significantly susceptible to PM1, PM2.5 and PM10. PM1/PM2.5 appeared stronger associations with ARD in HIV/AIDS patients aged over 60 years old and in the cold season.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Contaminantes Atmosféricos , Infecciones por VIH , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Contaminantes Atmosféricos/análisis , China/epidemiología , Exposición a Riesgos Ambientales/análisis , Infecciones por VIH/epidemiología , Material Particulado/efectos adversos , Material Particulado/análisis , Estudios Cruzados
14.
Methods Mol Biol ; 2587: 427-453, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36401042

RESUMEN

The CRISPR-Cas9 system has quickly become the standard tool for genome editing. To deliver this system to target cells, adeno-associated virus (AAV) vectors are commonly used. In fact, AAV vectors have been utilized to deliver the CRISPR-Cas9 system to induce genomic exon skipping and restore the dystrophin protein in various Duchenne muscular dystrophy model animals. Despite the high transduction efficiency, AAV vector-mediated delivery has several limitations, such as the packaging size, prolonged overexpression of Cas9, immunogenicity against the AAV capsid, and the risk of integrating a part of the AAV genomic sequence into the host cell. To overcome these issues, we have recently engineered a transient delivery system utilizing VSV-G pseudotyped extracellular vesicles (EVs) termed NanoMEDIC (nanomembrane-derived extracellular vesicles for the delivery of macromolecular cargo). NanoMEDIC utilizes an HIV-derived Gag protein to package Cas9 protein and gRNA into EVs. The Cas9 and Gag proteins are fused to a heterodimerizer and conditionally dimerized by the addition of an inducible chemical ligand to recruit Cas9 protein into EVs. sgRNA is packaged into EVs through an HIV-derived RNA packaging signal and is subsequently released by two self-cleaving ribozymes. Utilizing these features, NanoMEDIC can achieve highly efficient packaging of the Cas9 protein and gRNA for genome editing into a variety of target cells and in vivo. Here, we describe a step-by-step protocol, including the gRNA-expressing vector construction and large-scale NanoMEDIC production, for in vivo genome editing.


Asunto(s)
Vesículas Extracelulares , Infecciones por VIH , Animales , ARN Guia/genética , Sistemas CRISPR-Cas/genética , Proteína 9 Asociada a CRISPR/genética , Ribonucleoproteínas/genética , Exones/genética , Genómica , Vesículas Extracelulares/genética , Infecciones por VIH/genética
17.
PLoS One ; 17(11): e0276981, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36327305

RESUMEN

Understanding the structure of human sexual contact networks is vital in a broad range of disciplines, including sociology, biology, public health, and anthropology. However, sexual contact networks are yet to be understood because technical and privacy issues make it difficult to conduct accurate, large-scale surveys. In this study, we surveyed data openly available on one of the largest adult entertainment websites in Japan, where male clients (MCs) can write online customer reviews of female commercial sex workers (FCSWs). In particular, our investigation focused on a type of establishment called "soapland," the only type of sex industry in Japan where sexual intercourse is publicly permitted. Soaplands are scattered throughout Japan, and the study website covers approximately 66% of them. Using such a vast amount of data on a nationwide scale, we clarified the network structure of commercial sex, characterized by small-world, scale-free, and disassortative mating properties. To study geographical characteristics, we compared the resulting network with three different artificially generated networks via the random rewiring of links. Moreover, we considered a simple epidemic model on the resulting network, and investigated whether it would be more effective to provide infection control measures to FCSWs or MCs. We determined that active FCSWs constitute an important pathway of infection propagation in commercial sex networks, but MCs also play an essential role as weak ties.


Asunto(s)
Infecciones por VIH , Trabajo Sexual , Adulto , Masculino , Femenino , Humanos , Conducta Sexual , Coito , Japón , Infecciones por VIH/epidemiología , Parejas Sexuales
18.
Sci Rep ; 12(1): 18575, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36329104

RESUMEN

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position -168 of the promoter region of the protein kinase R (-168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants' heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.


Asunto(s)
Infecciones por VIH , Humanos , Estudios Longitudinales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Estudios Retrospectivos , Biomarcadores , Antivirales/uso terapéutico , eIF-2 Quinasa/metabolismo , Carga Viral
19.
Sci Rep ; 12(1): 18567, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36329160

RESUMEN

Inhibitors of histone deacetylases (HDACis) are major latency reversing agent (LRA) candidates in 'shock and kill' strategies to eradicate the HIV reservoir in infected patients. The poor achievements of initial HDACi-based trials and subsequent studies have highlighted the need for more efficient approaches such as combinatory and immunostimulating therapies. Here we studied combinations of IL-15 with pan-HDACi (Vorinostat, Romidepsin, Panobinostat) or class I selective-HDACi (Entinostat) with or without a PKC agonist (Prostratin) for their impact on in vitro reactivation and NK cell-mediated suppression of latent HIV. Results showed that pan-HDACis but not Entinostat reduced NK cell viability and function; yet, combined IL-15 reverted the negative effects of pan-HDACis except for Panobinostat. All HDACis were ineffective at reactivating HIV in a CD4+ T cell model of latency, with pan-HDACis suppressing spontaneous and IL-15- or Prostratin-induced HIV release, while IL-15 + Prostratin combination showed maximal activity. Moreover, Panobinostat impaired STAT5 and NF-κB activation by IL-15 and Prostratin, respectively. Finally, by using effectors (NK) and targets (latently infected CD4+ T cells) equally exposed to drug combinations, we found that IL-15-mediated suppression of HIV reactivation by NK cells was inhibited by Panobinostat. Our data raise concerns and encouragements for therapeutic application of IL-15/LRA combinations.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Latencia del Virus , VIH-1/fisiología , Panobinostat/farmacología , Panobinostat/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Interleucina-15/farmacología , Linfocitos T CD4-Positivos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Células Asesinas Naturales , Activación Viral
20.
BMC Health Serv Res ; 22(1): 1315, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36329450

RESUMEN

This cost-outcome study estimated, from the perspective of the service provider, the total annual cost per client on antiretroviral therapy (ART) and total annual cost per client virally suppressed (defined as < 1000 copies/ml at the time of the study) in Uganda in five ART differentiated service delivery models (DSDMs). These included both facility- and community-based models and the standard of care (SOC), known as the facility-based individual management (FBIM) model. The Ministry of Health (MOH) adopted guidelines for DSDMs in 2017 and sought to measure their costs and outcomes, in order to effectively plan for their resourcing, implementation, and scale-up. In Uganda, the standard of care (FBIM) is considered as a DSDM option for clients requiring specialized treatment and support, or for those who select not to join an alternative DSDM. Note that clients on second-line regimes and considered as "established on treatment" can join a suitable DSDM.Using retrospective client record review of a cohort of clients over a two-year period, with bottom-up collection of clients' resource utilization data, top-down collection of above-delivery level and delivery-level providers' fixed operational costs, and local unit costs. Forty-seven DSDMs located at facilities or community-based points in the four regions of Uganda were included in the study, with 653 adults on ART (> 18 years old) enrolled in a DSDM. The study found that retention in care was 98% for the sample as a whole [96-100%], and viral suppression, 91% [86-93%]. The mean cost to the provider (MOH or NGO implementers) was $152 per annum per client treated, ranging from $141 to $166. Differences among the models' costs were largely due to clients' ARV regimens and the proportions of clients on second line regimens. Service delivery costs, excluding ARVs, other medicines and laboratory tests, were modest, ranging from $9.66-16.43 per client per year. We conclude that differentiated ART service delivery in Uganda achieved excellent treatment outcomes at a cost similar to the standard of care. While large budgetary savings might not be immediately realized, the reallocation of "saved" staff time could improve health system efficiency and with their equivalent or better outcomes and large benefits to clients, client-centred differentiated models would nevertheless add great societal value.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Humanos , Adolescente , Uganda , Estudios Retrospectivos , Infecciones por VIH/tratamiento farmacológico , Programas de Gobierno , Fármacos Anti-VIH/uso terapéutico
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