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1.
AIDS Behav ; 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38457051

RESUMEN

Pre-exposure prophylaxis (PrEP) reduces sexual risk for HIV transmission by 99% when used appropriately, but remains underutilized among gay, bisexual, and other men who have sex with men (MSM). In this mixed-method study, we describe reasons for PrEP refusal associated with low self-perceived need for PrEP among MSM who recently declined daily oral PrEP when offered by a provider. Data are from a quantitative behavioral survey of MSM (N = 93) living in Atlanta, Chicago, and Raleigh-Durham, who also either responded to an in-depth interview (n = 51) or participated in one of 12 focus groups (n = 42). Themes of low self-perceived need for PrEP were: low self-perceived risk for HIV acquisition (33% of respondents); confidence in remaining HIV-negative (35%); using condoms (81%); limiting number of partners and choosing partners carefully (48%); asking partners about their HIV status before having sex (45%); engaging in safer sexual positions or oral sex (28%); being in a monogamous relationship or exclusivity with one partner (26%); and regular HIV testing (18%). Low self-perceived risk for HIV acquisition and high confidence in other prevention strategies were important factors related to low self-perceived need in MSM refusing daily oral PrEP when offered. Providers should continue to discuss the benefits of PrEP as a safe and highly effective option for HIV prevention.


RESUMEN: La profilaxis pre-exposición (PrEP) reduce el riesgo de transmisión sexual por el VIH en un 99% cuando se utiliza apropiadamente, pero sigue siendo subutilizada entre hombres gais, bisexuales y otros hombres que tienen sexo con hombres (HSH). En este estudio de método mixto, describimos los motivos del rechazo de la PrEP asociados a la baja necesidad autopercibida de la PrEP entre los HSH que recientemente rechazaron la PrEP oral diaria, cuando fue ofrecida por un proveedor de salud. Los datos provienen de una encuesta cuantitativa de comportamiento de los HSH (N = 93) que viven en Atlanta, Chicago y Raleigh-Durham, quienes también respondieron a una entrevista en profundidad (n = 51) o participaron en uno de los 12 grupos focales (n = 42). Los temas de baja necesidad autopercibida del uso de la PrEP fueron: el bajo riesgo auto percibido de contraer el VIH (33% de los encuestados); la confianza en seguir siendo VIH negativo (35%); utilizar condones (81%); limitar el número de parejas sexuales y elegir las parejas cuidadosamente (48%); preguntar a sus parejas sobre su estado de VIH antes de tener relaciones sexuales (45%); participar en posiciones sexuales más seguras o sexo oral (28%); estar en relación monógama o de exclusividad con una sola pareja (26%); y hacerse pruebas del VIH regularmente (18%). El bajo riesgo autopercibido de contraer el VIH y la alta confianza en otras estrategias de prevención fueron factores importantes relacionados con la baja necesidad autopercibida en los HSH que rechazaron la PrEP oral diaria cuando se les ofreció. Los proveedores de salud deben continuar el diálogo sobre los beneficios de la PrEP como una opción segura y altamente eficaz para la prevención del VIH.

2.
Microbiol Spectr ; 12(4): e0358623, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38391232

RESUMEN

Although smallpox has been eradicated, other orthopoxviruses continue to be a public health concern as exemplified by the ongoing Mpox (formerly monkeypox) global outbreak. While medical countermeasures (MCMs) previously approved by the Food and Drug Administration for the treatment of smallpox have been adopted for Mpox, previously described vulnerabilities coupled with the questionable benefit of at least one of the therapeutics during the 2022 Mpox outbreak reinforce the need for identifying and developing other MCMs against orthopoxviruses. Here, we screened a panel of Merck proprietary small molecules and identified a novel nucleoside inhibitor with potent broad-spectrum antiviral activity against multiple orthopoxviruses. Efficacy testing of a 7-day dosing regimen of the orally administered nucleoside in a murine model of severe orthopoxvirus infection yielded a dose-dependent increase in survival. Treated animals had greatly reduced lesions in the lung and nasal cavity, particularly in the 10 µg/mL dosing group. Viral levels were also markedly lower in the UMM-766-treated animals. This work demonstrates that this nucleoside analog has anti-orthopoxvirus efficacy and can protect against severe disease in a murine orthopox model.IMPORTANCEThe recent monkeypox virus pandemic demonstrates that members of the orthopoxvirus, which also includes variola virus, which causes smallpox, remain a public health issue. While currently FDA-approved treatment options exist, risks that resistant strains of orthopoxviruses may arise are a great concern. Thus, continued exploration of anti-poxvirus treatments is warranted. Here, we developed a template for a high-throughput screening assay to identify anti-poxvirus small-molecule drugs. By screening available drug libraries, we identified a compound that inhibited orthopoxvirus replication in cell culture. We then showed that this drug can protect animals against severe disease. Our findings here support the use of existing drug libraries to identify orthopoxvirus-targeting drugs that may serve as human-safe products to thwart future outbreaks.


Asunto(s)
Mpox , Orthopoxvirus , Viruela , Virus de la Viruela , Animales , Ratones , Humanos , Nucleósidos/uso terapéutico , Viruela/tratamiento farmacológico , Viruela/prevención & control , Modelos Animales de Enfermedad
3.
Cureus ; 15(7): e41503, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37551248

RESUMEN

Rare developmental anomalies known as urachal remnants are brought on by flaws in the foetal developmental process. However, depending on the location and degree of incomplete obliteration, the urachus can undergo a variety of urachal anomalies. An umbilical fistulogram and a voiding cystourethrogram both supported the existence of the adult urachal cyst in this case. To treat the sepsis, we provided the patient with antibiotics first, then a surgical procedure. The entire vesico-umbilical tract with the urachal cyst was removed using the open approach. The excised specimen's histology revealed a foreign body giant cell reaction without any indication of malignancy. The presentation and diagnosis of vesico-umbilical urinary fistula (VUUF) in adults can occasionally be difficult. They happen very rarely. So we began putting forward this case for the same reason.

4.
Bioorg Med Chem Lett ; 94: 129432, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37591319

RESUMEN

Nucleoside and nucleobase analogs capable of interfering with nucleic acid synthesis have played essential roles in fighting infectious diseases. However, many of these agents are associated with important and potentially lethal off-target intracellular effects that limit their use. Based on the previous discovery of base-modified 2'-deoxyuridines, which showed high anticancer activity while exhibiting lower toxicity toward rapidly dividing normal human cells compared to antimetabolite chemotherapeutics, we hypothesized that a similar modification of the N4-hydroxycytidine (NHC) molecule would provide novel antiviral compounds with diminished side effects. This presumption is due to the substantial structural difference with natural cytidine leading to less recognizability by host cell enzymes. Among the 42 antimetabolite species that have been synthesized and screened against VEEV, one hit compound was identified. The structural features of the modifying moiety were similar to those of the anticancer lead 2'-deoxyuridine derivative reported previously, providing an opportunity to pursue further structure-activity relationship (SAR) studies directed to lead improvement, and obtain insight into the mechanism of action, which can lead to identifying drug candidates against a broad spectrum of RNA viral infections.


Asunto(s)
Virus de la Encefalitis Equina Venezolana , Animales , Humanos , Antimetabolitos , Antivirales/farmacología , Desoxiuridina , Caballos , Inmunosupresores
5.
AIDS ; 37(12): 1912-1914, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37646592

RESUMEN

In 2021, there were an estimated 153 500 persons aged at least 13 years with undiagnosed HIV infection. Estimated rates among Black/African American, Hispanic/Latino, and White persons were used to assess disparity trends from 2017 to 2021. Rates decreased across two absolute and relative disparity measures. Despite these declines, Black and Hispanic persons had rates 8.3 and 4.2 times the rate of White persons in 2021. Increased testing and innovative efforts are needed to address HIV-related disparities.


Asunto(s)
Infecciones por VIH , Adolescente , Adulto , Humanos , Negro o Afroamericano , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Grupos Raciales , Estados Unidos/epidemiología , Blanco , Hispánicos o Latinos
6.
MMWR Morb Mortal Wkly Rep ; 72(23): 627-632, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37289660

RESUMEN

More than 30,000 monkeypox (mpox) cases were reported in the United States during the 2022 multinational outbreak; cases disproportionately affected gay, bisexual, and other men who have sex with men (MSM). Substantial racial and ethnic disparities in incidence were also reported (1). The national mpox vaccination strategy* emphasizes that efforts to administer the JYNNEOS mpox vaccine should be focused among the populations at elevated risk for exposure to mpox (2). During May 2022-April 2023, a total of 748,329 first JYNNEOS vaccine doses (of the two recommended) were administered in the United States.† During the initial months of the outbreak, lower vaccination coverage rates among racial and ethnic minority groups were reported (1,3); however, after implementation of initiatives developed to expand access to mpox vaccination,§ coverage among racial and ethnic minority groups increased (1,4). A shortfall analysis was conducted to examine whether the increase in mpox vaccination coverage was equitable across all racial and ethnic groups (5). Shortfall was defined as the percentage of the vaccine-eligible population that did not receive the vaccine (i.e., 100% minus the percentage of the eligible population that did receive a first dose). Monthly mpox vaccination shortfalls were calculated and were stratified by race and ethnicity; monthly percent reductions in shortfall were also calculated compared with the preceding month's shortfall (6). The mpox vaccination shortfall decreased among all racial and ethnic groups during May 2022-April 2023; however, based on analysis of vaccine administration data with race and ethnicity reported, 66.0% of vaccine-eligible persons remained unvaccinated at the end of this period. The shortfall was largest among non-Hispanic Black or African American (Black) (77.9%) and non-Hispanic American Indian or Alaska Native (AI/AN) (74.5%) persons, followed by non-Hispanic White (White) (66.6%) and Hispanic or Latino (Hispanic) (63.0%) persons, and was lowest among non-Hispanic Asian (Asian) (38.5%) and non-Hispanic Native Hawaiian and other Pacific Islander (NH/OPI) (43.7%) persons. The largest percentage decreases in the shortfall were achieved during August (17.7%) and September (8.5%). However, during these months, smaller percentage decreases were achieved among Black persons (12.2% and 4.9%, respectively), highlighting the need for a focus on equity for the entirety of a public health response. Achieving equitable progress in JYNNEOS vaccination coverage will require substantial decreases in shortfalls among Black and AI/AN persons.


Asunto(s)
Mpox , Minorías Sexuales y de Género , Vacuna contra Viruela , Masculino , Humanos , Estados Unidos/epidemiología , Etnicidad , Homosexualidad Masculina , Cobertura de Vacunación , Grupos Minoritarios , Vacunación
7.
AIDS Behav ; 27(11): 3623-3631, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37166687

RESUMEN

Experiences with stigma and discrimination in healthcare settings are associated with negative health outcome for persons with HIV (PWH). PWH may experience discrimination due to the intersection of multiple marginalized social identities. Describing these experiences is important for informing interventions and strategies to reduce stigma and discrimination. We report experiences with discrimination in HIV healthcare settings attributed to multiple characteristics, e.g., sexual orientation, race/ethnicity, income, or social class, and/or injection drug use, among a nationally representative sample of persons with diagnosed HIV in the United States using data from the Medical Monitoring Project (MMP). We calculated weighted prevalences and associated 95% confidence intervals for any discrimination and discrimination attributed to multiple characteristics (intersectional discrimination). Among those experiencing discrimination, nearly 1 in 4 persons reported intersectional discrimination, with a higher burden among key populations of focus for HIV prevention and treatment. Discrimination was attributed to HIV status (62.5%), sexual orientation (60.4%), and race/ethnicity (54.3%). Persons who experienced intersectional discrimination were less likely to have a regular HIV care provider, have trust in HIV care or treatment information from healthcare providers, and be antiretroviral treatment or HIV care visit adherent. Future studies should explore methods to operationalize and assess experiences with intersectional stigma and discrimination and use the outcomes to inform qualitative research that provides more context and a deeper understanding of experiences with intersectional discrimination among PWH.

8.
MMWR Morb Mortal Wkly Rep ; 72(15): 398-403, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37053122

RESUMEN

As of December 31, 2022, a total of 29,939 monkeypox (mpox) cases* had been reported in the United States, 93.3% of which occurred in adult males. During May 10-December 31, 2022, 723,112 persons in the United States received the first dose in a 2-dose mpox (JYNNEOS)† vaccination series; 89.7% of these doses were administered to males (1). The current mpox outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and racial and ethnic minority groups (1,2). To examine racial and ethnic disparities in mpox incidence and vaccination rates, rate ratios (RRs) for incidence and vaccination rates and vaccination-to-case ratios were calculated, and trends in these measures were assessed among males aged ≥18 years (males) (3). Incidence in males in all racial and ethnic minority groups except non-Hispanic Asian (Asian) males was higher than that among non-Hispanic White (White) males. At the peak of the outbreak in August 2022, incidences among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) males were higher than incidence among White males (RR = 6.9 and 4.1, respectively). Overall, vaccination rates were higher among males in racial and ethnic minority groups than among White males. However, the vaccination-to-case ratio was lower among Black (8.8) and Hispanic (16.2) males than among White males (42.5) during the full analytic period, indicating that vaccination rates among Black and Hispanic males were not proportionate to the elevated incidence rates (i.e., these groups had a higher unmet vaccination need). Efforts to increase vaccination among Black and Hispanic males might have resulted in the observed relative increased rates of vaccination; however, these increases were only partially successful in reducing overall incidence disparities. Continued implementation of equity-based vaccination strategies is needed to further increase vaccination rates and reduce the incidence of mpox among all racial and ethnic groups. Recent modeling data (4) showing that, based on current vaccination coverage levels, many U.S. jurisdictions are vulnerable to resurgent mpox outbreaks, underscore the need for continued vaccination efforts, particularly among racial and ethnic minority groups.


Asunto(s)
Mpox , Minorías Sexuales y de Género , Masculino , Adulto , Humanos , Estados Unidos/epidemiología , Adolescente , Etnicidad , Homosexualidad Masculina , Grupos Minoritarios , Vacunación , Blanco
9.
Child Adolesc Psychiatry Ment Health ; 17(1): 40, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922846

RESUMEN

BACKGROUND: Development of emotional distress (ED) among adolescents living with perinatally acquired HIV (ALPHIV) affects their adherence behaviour and social and psychological functioning. Data on stressors among ALPHIV demonstrates the gap on the predictors of ED experienced by 'perinatally infected ALHIV' in the Indian socio-cultural milieu. This study aimed to identify the predictors of ED and examine their mediating and moderating role in the development of ED among Indian ALPHIV. METHODS: Utilizing the sequential exploratory mixed-methods design, 43 qualitative interviews were conducted with ALPHIV, parents/guardians, and health care providers, followed by the cross-sectional survey among 100 ALPHIV (10-19 years). The distress subscale of the Weinberger Adjustment Inventory was used to measure ED. Qualitative data, analyzed using grounded theory were utilized to develop a survey tool. Bivariate and regression analyses were conducted to identify predictors of ED. Mediation and moderation models were tested to examine underlying mechanisms associated with ED. The study was approved by the institutional ethics committee. RESULTS: Strong parental control, compulsive asexuality, perceived negatively different from peers, and anger toward parents were the major themes emerging from the qualitative component which eventually led to survey tool domains viz., HIV awareness, parental control, hypervigilance, adolescent-parent relationship, adolescent-parent communication, body image and perceived negatively different from peers (PNDP). Quantitative analysis indicated high ED among ALPHIV and ED was significantly associated with PNDP, anger, body image, and hypervigilance. The relationship between PNDP and ED was significantly mediated by anger, and moderated by body image and hypervigilance. CONCLUSIONS: The study stresses the need for early mental health interventions for Indian ALPHIV before an ALPHIV develops ED. Focused counseling on anger assessment, body image issues, and self-perception is critical for leading a 'normal' life by ALPHIV. Besides, skill building of primary caregivers is recommended to draw a line between protection and overprotection.

11.
Antiviral Res ; 210: 105513, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36592670

RESUMEN

Antibody-based therapy is emerging as a critical therapeutic countermeasure to treat acute viral infections by offering rapid protection against clinical disease. The advancements in structural biology made it feasible to rationalize monoclonal antibodies (mAbs) by identifying key and, possibly, neutralizing epitopes of viral proteins for therapeutic purposes. A critical component in assessing mAbs during pandemics requires the development of rapid but detailed methods to detect and quantitate the neutralization activity. In this study, we developed and optimized two high-content image (HCI)-based assays: one to detect viral proteins by staining and the second to quantify cytopathic viral effects by a label-free phenotypic assay. These assays were employed to screen for therapeutic antibodies against the monkeypox virus (MPXV) using surrogate poxviruses such as vaccinia virus (VACV). Plaque-based neutralization results confirmed the HCI data. The phenotypic assay found pox virus-induced syncytia formation in various cells, and we were able to quantitate and use this phenotype to screen mAbs. The HCI identified several potent VACV-neutralizing antibodies that showed in vitro efficacy against both clades of MPXV. In addition, a combination study of ST-246/tecovirimat/TPOXX a single neutralizing antibody Ab-40, showed synergistic activity against VACV in an in-vitro neutralization assay. This rapid high-content method utilizing state-of-the-art technologies enabled the evaluation of hundreds of mAbs quickly to identify several potent anti-MPXV neutralizing mAbs for further development.


Asunto(s)
Anticuerpos Antivirales , Monkeypox virus , Anticuerpos Neutralizantes , Virus Vaccinia/genética , Proteínas Virales , Anticuerpos Monoclonales/farmacología , Pruebas de Neutralización
12.
Lancet HIV ; 10(2): e134-e142, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36525980

RESUMEN

Expanding on previous work, we present an HIV Prevention Cycle of Care model to facilitate understanding of the complexity of issues involved in pre-exposure prophylaxis implementation for gay, bisexual, and other men who have sex with men (MSM) in the USA, including individual, client-provider, and overarching issues such as health equity, stigma, and prevention nomenclature. The HIV prevention cycle of care applies to MSM who test negative for HIV. The Prevention Cycle of Care model includes seven steps: prevention knowledge, prevention self-awareness and preferences, prevention motivation, health-care access and cost, provider issues, adherence and persistence, and periodic reassessment and adjustment. HIV prevention is complex in an era of emerging multiple modalities, and more research is needed to successfully implement pre-exposure prophylaxis options over time and across diverse communities of MSM who are sexually active.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Conducta Sexual
13.
J Acquir Immune Defic Syndr ; 92(3): 212-216, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36442153

RESUMEN

BACKGROUND: An important subgroup of gay, bisexual, and other men who have sex with men (MSM) with behavioral indications refuse daily oral pre-exposure prophylaxis (PrEP) when recommended by a provider. Emerging HIV prophylaxis products (eg, injectable, event-driven) offer more options to MSM who refuse daily PrEP. In this article, we assess reasons for refusal and likelihood to use various products among MSM who refused PrEP. METHODS: MSM who reported anal sex without condoms or PrEP and refused daily oral PrEP in the past 6 months were recruited through clinics, community venues, and online in Atlanta, Chicago, and Raleigh-Durham. Men were asked their main reason for recently refusing daily PrEP and likelihood of using various PrEP options in the future. Bivariate and multivariable regression models were used to estimate associations. RESULTS: MSM (n = 93; 70% Black, 48% age 18-29 years) reported their main reason for refusing daily PrEP were potential side effects (35%), a daily pill regimen (22%), and not having enough information (18%). Reported likelihood of using PrEP products was 58% for penile gel, 54% for event-driven oral, 52% for injectable, and 50% for daily PrEP. MSM who reported daily regimen as the main reason for refusing PrEP had greater odds of likelihood to use an injectable [adjusted odds ratio (AOR) = 5.21, 95% confidence interval (CI): 1.32 to 20.52]. Younger men (18-29 vs 30+ years) had greater odds of likelihood to use condoms (AOR = 3.40, 95% CI: 1.15 to 10.04) and daily PrEP (AOR = 2.76, 95% CI: 1.06 to 7.16); there were no product preference differences by race. CONCLUSION: Most men who refused daily PrEP indicated likelihood of using some form of PrEP in the future.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Homosexualidad Masculina , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Conducta Sexual
14.
Public Health Rep ; 138(5): 771-781, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36129230

RESUMEN

OBJECTIVE: Transgender women with diagnosed HIV experience social and structural factors that could negatively affect their overall health and HIV-related health outcomes. We describe estimates from the Centers for Disease Control and Prevention Medical Monitoring Project (MMP) of sociodemographic characteristics, HIV stigma, discrimination, and mental health outcomes among transgender women with diagnosed HIV. METHODS: We analyzed pooled data of all transgender women with diagnosed HIV (N = 217) from the 2015 through 2018 MMP cycles. We reported unweighted frequencies, weighted percentages, and 95% CIs for all characteristics. We post-stratified data to known population totals by age, race and ethnicity, and sex at birth from the National HIV Surveillance System. RESULTS: Approximately 46% of transgender women with diagnosed HIV identified as Black or African American, 67% lived at or below the federal poverty level, 18% had experienced homelessness in the past year, 26% experienced mild to severe symptoms of depression, 30% experienced mild to severe anxiety symptoms, 32% reported physical violence by an intimate partner, and 30% reported forced sex during their lifetime. Despite 80% being very satisfied with their current HIV care, 94% experienced current HIV stigma and 20% experienced health care-related discrimination since being diagnosed with HIV. Among transgender women with diagnosed HIV who experienced discrimination, 46% and 51% experienced health care discrimination attributed to their gender and sexual orientation or sexual practices, respectively. CONCLUSIONS: Our findings underscore a need to address unmet ancillary services, such as housing, intimate partner violence, and mental health needs, and the need for strategies to reduce experiences with HIV stigma and discrimination in care for transgender women with diagnosed HIV in the United States.

15.
AIDS ; 36(2): 305-315, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34690282

RESUMEN

OBJECTIVES: HIV prevalence is an estimated 14% among transgender women (TW) and 3% among transgender men (TM). HIV care is vital for viral suppression but is hindered by transphobia and HIV stigma. We assessed HIV care outcomes among transgender persons (TG) with HIV in the United States. DESIGN: Systematic review and meta-analysis of peer-reviewed journal articles. METHODS: We searched multiple electronic databases and Centers for Disease Control and Prevention's HIV Prevention Research Synthesis database for 2006-September 2020. Eligible reports were US-based studies that included TG and reported HIV care outcomes. Random-effects models were used to calculate HIV care outcome rates. The protocol is registered with PROSPERO (CRD42018079564). RESULTS: Few studies reported outcomes for TM; therefore, only TW meta-analysis results are reported. Fifty studies were identified having low-to-medium risk-of-bias scores. Among TW with HIV, 82% had ever received HIV care; 72% were receiving care, and 83% of those were retained in HIV care. Sixty-two percent were currently virally suppressed. Among those receiving HIV care or antiretroviral therapy (ART), 67% were virally suppressed at last test. Sixty-five percent were linked to HIV care 3 months or less after diagnosis. Seventy-one percent had ever been prescribed ART. Approximately 66% were taking ART, and 66% were ART-adherent. Only 56% were currently adherent the previous year. CONCLUSIONS: HIV care outcomes for TW were not ideal, and research gaps exists for TM. High heterogeneity was observed; therefore, caution should be taken interpreting the findings. Integrating transgender-specific health needs are needed to improve outcomes of transgender persons across the HIV care continuum.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Personas Transgénero , Continuidad de la Atención al Paciente , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Estados Unidos/epidemiología
16.
Front Pharmacol ; 12: 763950, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34646144

RESUMEN

Botulinum neurotoxins (BoNTs) are known as the most potent bacterial toxins, which can cause potentially deadly disease botulism. BoNT Serotype A (BoNT/A) is the most studied serotype as it is responsible for most human botulism cases, and its formulations are extensively utilized in clinics for therapeutic and cosmetic applications. BoNT/A has the longest-lasting effect in neurons compared to other serotypes, and there has been high interest in understanding how BoNT/A manages to escape protein degradation machinery in neurons for months. Recent work demonstrated that an E3 ligase, HECTD2, leads to efficient ubiquitination of the BoNT/A Light Chain (A/LC); however, the dominant activity of a deubiquitinase (DUB), VCIP135, inhibits the degradation of the enzymatic component. Another DUB, USP9X, was also identified as a potential indirect contributor to A/LC degradation. In this study, we screened a focused ubiquitin-proteasome pathway inhibitor library, including VCIP135 and USP9X inhibitors, and identified ten potential lead compounds affecting BoNT/A mediated SNAP-25 cleavage in neurons in pre-intoxication conditions. We then tested the dose-dependent effects of the compounds and their potential toxic effects in cells. A subset of the lead compounds demonstrated efficacy on the stability and ubiquitination of A/LC in cells. Three of the compounds, WP1130 (degrasyn), PR-619, and Celastrol, further demonstrated efficacy against BoNT/A holotoxin in an in vitro post-intoxication model. Excitingly, PR-619 and WP1130 are known inhibitors of VCIP135 and USP9X, respectively. Modulation of BoNT turnover in cells by small molecules can potentially lead to the development of effective countermeasures against botulism.

17.
Prev Med ; 150: 106682, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34119594

RESUMEN

Substance use is strongly associated with suicide completions. However, little is known about the patterns of substances used in suicide deaths. The purpose of this analysis is to determine latent classes of toxicology-reported substances among individuals who completed suicide. The sample consists of suicide victims in the National Violent Death Reporting System (NVDRS) during years 2003-2017 (n = 202,838). Toxicology reports were used to construct latent class analyses of substance use among suicide victims. Correlates for latent class membership included sex, race/ethnicity, previous experiences of child abuse, homelessness, and intimate partner violence (IPV) victimization. The majority of suicide victims were male (77.7%), straight/heterosexual (99.5%) and white (88.3%). The final unconditional model yielded a four-class model, including a "No substance/single substance use" class, an "Alcohol and other substance" class, a "Marijuana and other substance" class, and an "Opiate use" class. Compared to the reference class of "No substance/single substance," females were more likely than males to be classified in the "Alcohol and other substance" class, the "Multi-substance use" class, and the "Opiate use" class. Homelessness was associated with classification in the "Marijuana and other substance" class and the "Opiate use" class compared to the "No substance/single substance" class. IPV was associated with both polysubstance use classes ("Alcohol plus other substance" and "Marijuana plus other substance") along with the "Opiate use" class compared to the "No substance/single substance" class. These classes highlight profiles of suicide descendants and emphasize the importance of polysubstance use prevention among females, homeless individuals, and those who experience IPV.


Asunto(s)
Trastornos Relacionados con Sustancias , Suicidio , Causas de Muerte , Niño , Femenino , Homicidio , Humanos , Análisis de Clases Latentes , Masculino , Vigilancia de la Población , Violencia
18.
AIDS Patient Care STDS ; 35(5): 158-166, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33901403

RESUMEN

HIV pre-exposure prophylaxis (PrEP) is a preventive medication that could reduce new infections among men who have sex with men (MSM). There are limited data on differing reasons for PrEP nonuse by condomless anal sex (CAS). We examined demographic and behavioral variables associated with PrEP use and reasons for PrEP nonuse by CAS. Data are from the M-cubed Study, collected in a 2018 baseline assessment of MSM (n = 798) in Atlanta, Detroit, and New York City. Participants reported current PrEP use (31%), previous use (8%), and never use (61%). MSM reporting CAS [adjusted odds ratio (aOR) = 2.60, confidence interval (95% CI) = 1.73-3.91], age 18-29 (aOR = 2.11, 95% CI = 1.26-3.52), 30-39 (aOR = 2.12, 95% CI = 1.25-3.59), with a college degree (aOR = 1.96, 95% CI = 1.20-3.21), or postgraduate education (aOR = 2.58, 95% CI = 1.51-4.40) had greater odds of current (vs. never) use; uninsured (aOR = 0.30, 95% CI = 0.16-0.57) men had lower odds of current (vs. never) use. For never use, more MSM who reported CAS (vs. did not) endorsed the following reasons (p's < 0.05): Insurance wouldn't cover PrEP (20% vs. 12%), Didn't know where to get it (33% vs. 24%) and fewer reported Didn't need PrEP (23% vs. 39%) and Started a committed relationship (7% vs. 25%). For discontinuation, more MSM who reported CAS (vs. did not) endorsed Worry about the safety of PrEP (19% vs. 3%). Efforts are needed to enhance PrEP as an option among older, less educated, and uninsured MSM. These findings may inform how providers can facilitate PrEP use by messaging on access and safety for MSM who reported CAS.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Adolescente , Adulto , Ciudades , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Ciudad de Nueva York/epidemiología , Conducta Sexual , Adulto Joven
19.
J Int AIDS Soc ; 24(1): e25664, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33481359

RESUMEN

BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) is available and recommended for men who have sex with men (MSM) at risk for HIV infection. Other HIV prevention products are being developed, including long-acting injectable (LAI) and event-based oral and topical formulations. Understanding preferences for potential products by MSM can help direct further development of prevention messaging. METHODS: We present baseline data from HIV-negative participants enrolled in the US Mobile Messaging for Men (M-cubed) Study. Participants were asked their likelihood of and rank order preference for using daily oral PrEP and various potential prevention products (one- to -three-month injections, 2-1-1 sexual event oral dosing, anal or penile gel, or anal suppository), and their sociodemographic characteristics. Bivariate and multivariable logistics regression assessed demographic associations with likelihood of use and rank order preference. RESULTS: Overall, most MSM reported a likelihood of using LAI (74%), sexual event-based pills (67%) and penile gel (64%). Men who reported recent unprotected (condomless and PrEPless) anal sex most preferred a penile gel formulation (74%), followed closely by LAI and event-based pills (73% each). Current PrEP users (vs. non-users) had greater odds of reporting likelihood to use LAI (AOR = 3.29, 95% CI = 2.12 to 5.11), whereas men reporting recent unprotected anal sex had a greater odds of likelihood to use a penile gel (AOR = 1.79, 95% CI = 1.27 to 2.52) and an anal suppository (AOR = 1.48, 95% CI = 1.08 to 2.02). Hispanic/Latino (vs. White) MSM (AOR = 2.29, 95% CI = 1.40 to 3.73) and, marginally, Black MSM (AOR = 1.54, 95% CI = 1.00 to 2.38) had greater odds of reporting likelihood to use penile gel. Similar patterns were found for rank ordering preference of products, including condoms. CONCLUSIONS: Most MSM were interested in using various potential future HIV prevention products, especially LAI. However, two typologies of potential users emerged: men who prefer sexual event-based methods (condoms, event-based pill, sexual gels and suppositories) and men who prefer non-sexual event-based methods (daily pill, LAI). Men who reported recent unprotected anal sex preferred a penile gel product most, followed closely by sexual event-based pills and LAI. Racial/ethnic differences were noted as well. These findings on product preferences can help in formulation development and messaging.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Adulto , Negro o Afroamericano , Condones , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Profilaxis Pre-Exposición/métodos , Conducta Sexual , Adulto Joven
20.
Chemosphere ; 269: 129372, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33383253

RESUMEN

The current technologies to treat hypersaline produced water (PW), such as thermal evaporation, are usually energy-intensive and cost-prohibitive. This study developed a low-cost, robust, solar-driven carbon black and airlaid paper-based evaporator (CAPER) for desalination of PW in the Permian Basin, United States. The study aims to better understand the removal of aromatic organic compounds and heavy metals during solar distillation, water output, and heat transfer. Outdoor experiments using CAPER assisted with polystyrene foam in a single slope, single basin solar still achieved an enhanced average evaporation rate of 2.23 L per m2 per day, 165% higher than that of a conventional solar still. Analysis of heat transfer models demonstrated that CAPER solar evaporation achieved an evaporative heat transfer coefficient of ∼28.9 W m-2·K-1, 27.9% higher than without CAPER. The maximum fractional energy of evaporation and convection heat transfer inside the solar still with and without CAPER was ∼81.4% and ∼78.2%, respectively. For the PW with a total dissolved solids concentration of 134 g L-1, solar distillation removed 99.97% salts and over 98% heavy metals. The high removal efficiency of 99.99% was achieved for Ca, Na, Mg, Mn, Ni, Se, Sr, and V. Organic characterization revealed that solar distillation removed over 83% aromatic compounds. Solar desalination using CAPER provides a low-cost and high-performance process to treat PW with high salinity and complex water chemistry for potential fit-for-purpose beneficial uses.


Asunto(s)
Purificación del Agua , Destilación , Hollín , Agua
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