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1.
PLoS Pathog ; 19(5): e1011219, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37253061

RESUMEN

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.


Asunto(s)
Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Masculino , Humanos , Enfermedades de Transmisión Sexual/complicaciones , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/terapia , Homosexualidad Masculina , ARN Ribosómico 16S , Infecciones por Chlamydia/complicaciones , Infecciones por VIH/complicaciones , Gonorrea/epidemiología
2.
J Infect Dis ; 229(Supplement_2): S234-S242, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38001044

RESUMEN

BACKGROUND: In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH). METHODS: We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox. RESULTS: Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200 copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01-6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200 copies/mL had 2.10 (95% CI, 1.00-4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis. CONCLUSIONS: PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment.


Asunto(s)
Infecciones por VIH , Mpox , Estados Unidos , Masculino , Humanos , Benzamidas , Recuento de Linfocito CD4 , Centers for Disease Control and Prevention, U.S.
3.
Clin Infect Dis ; 78(2): 411-413, 2024 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-37596931

RESUMEN

The human immunodeficiency virus (HIV) workforce continues to face a crisis, particularly in the southern United States. Adding to known issues of administrative burden and less competitive compensation, recent anti- lesbian, gay, bisexual, transgender and queer (LGBTQ+) legislation threatens the already strained HIV workforce. HIV care providers advocate for all aspects of their patient's lives, including those needing gender-affirming care. The recent legislative targets against transgender patients, which involves many people with HIV, will clearly add to the burden on individual HIV care providers and therefore the HIV workforce. Recruitment and retention efforts in states impacted by these laws will become increasingly difficult without advocacy for the patients we serve. The HIV workforce must work together with LGBTQ+ populations to address these recent laws and promote the well-being of all our patients and colleagues.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Personas Transgénero , Femenino , Humanos , Estados Unidos , VIH , Conducta Sexual , Recursos Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control
4.
Emerg Infect Dis ; 30(2): 245-254, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38270128

RESUMEN

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 US communities. Survey-weighted estimates of SARS-CoV-2 infection and vaccine willingness among participants at each site were compared within demographic groups by using linear regression models with inverse variance weighting. Among 22,284 persons >2 months of age and older, median prevalence of infection (prior, active, or both) was 12.9% across sites and similar across age groups. Within each site, average prevalence of infection was 3 percentage points higher for Black than White persons and average vaccine willingness was 10 percentage points lower for Black than White persons and 7 percentage points lower for Black persons than for persons in other racial groups. The higher prevalence of SARS-CoV-2 infection among groups with lower vaccine willingness highlights the disparate effect of COVID-19 and its complications.


Asunto(s)
COVID-19 , Vacunas , Adulto , Niño , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Estudios Transversales , Prevalencia , Estudios Seroepidemiológicos
5.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-34379922

RESUMEN

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Asunto(s)
Infecciones por VIH/prevención & control , Inhibidores de Integrasa VIH/administración & dosificación , Profilaxis Pre-Exposición , Piridonas/administración & dosificación , Tenofovir/uso terapéutico , Administración Oral , Adulto , Anciano , Fármacos Anti-VIH/uso terapéutico , Preparaciones de Acción Retardada/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Resistencia a Medicamentos/genética , Femenino , Inhibidores de Integrasa VIH/efectos adversos , Homosexualidad Masculina , Humanos , Inyecciones Intramusculares/efectos adversos , Análisis de Intención de Tratar , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Piridonas/efectos adversos , Personas Transgénero , Adulto Joven
6.
J Infect Dis ; 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38019956

RESUMEN

BACKGROUND: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development. METHODS: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture. RESULTS: Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males. CONCLUSIONS: The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process. CLINICAL TRIALS REGISTRATION: NCT01868464 (ClinicalTrials.gov).

7.
Thorax ; 78(6): 606-616, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35793833

RESUMEN

OBJECTIVE: COVID-19 severity is correlated with granulocyte macrophage colony-stimulating factor (GM-CSF) and C reactive protein (CRP) levels. In the phase three LIVE-AIR trial, lenzilumab an anti-GM-CSF monoclonal antibody, improved the likelihood of survival without ventilation (SWOV) in COVID-19, with the greatest effect in participants having baseline CRP below a median of 79 mg/L. Herein, the utility of baseline CRP to guide lenzilumab treatment was assessed. DESIGN: A subanalysis of the randomised, blinded, controlled, LIVE-AIR trial in which lenzilumab or placebo was administered on day 0 and participants were followed through Day 28. PARTICIPANTS: Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. INTERVENTIONS: Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. MAIN OUTCOME MEASURES: The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. RESULTS: SWOV was achieved in 152 (90%; 95% CI 85 to 94) lenzilumab and 144 (79%; 72 to 84) placebo-treated participants with baseline CRP <150 mg/L (HR: 2.54; 95% CI 1.46 to 4.41; p=0.0009) but not with CRP ≥150 mg/L (HR: 1.04; 95% CI 0.51 to 2.14; p=0.9058). A statistically significant interaction between CRP and lenzilumab treatment was observed (p=0.044). Grade ≥3 adverse events with lenzilumab were comparable to placebo in both CRP strata. No treatment-emergent serious adverse events were attributed to lenzilumab. CONCLUSION: Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. TRIAL REGISTRATION NUMBER: NCT04351152; ClinicalTrials.gov.


Asunto(s)
COVID-19 , Humanos , Proteína C-Reactiva , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores
8.
J Antimicrob Chemother ; 78(2): 497-503, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36512383

RESUMEN

BACKGROUND: Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM. MATERIALS AND METHODS: Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18-49 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS. RESULTS: Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164-456) ng/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38-13.51) ng/mg] were greater than bictegravir concentrations [0.27 (0.15-0.70) ng/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions. CONCLUSIONS: Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Inhibidores de Integrasa VIH , Minorías Sexuales y de Género , Humanos , Masculino , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Emtricitabina/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Inhibidores de Integrasa VIH/uso terapéutico , Homosexualidad Masculina , Integrasas , Piridonas/uso terapéutico , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad
9.
Curr HIV/AIDS Rep ; 20(4): 261-269, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37178205

RESUMEN

PURPOSE OF REVIEW: We reviewed the available literature on mpox in People with HIV (PWH). We highlight special considerations of mpox infection related to epidemiology, clinical presentation, diagnostic and treatment considerations, prevention, and public health messaging in PWH. RECENT FINDINGS: During the 2022 mpox outbreak, PWH were disproportionally impacted worldwide. Recent reports suggest that the disease presentation, management, and prognosis of these patients, especially those with advanced HIV disease, can widely differ from those without HIV-associated immunodeficiency. Mpox can often be mild and resolve on its own in PWH with controlled viremia and higher CD4 counts. However, it can be severe, with necrotic skin lesions and protracted healing; anogenital, rectal, and other mucosal lesions; and disseminated organ systems involvement. Higher rates of healthcare utilization are seen in PWH. Supportive, symptomatic care and single or combination mpox-directed antiviral drugs are commonly used in PWH with severe mpox disease. Data from randomized clinical control trials on the efficacy of therapeutic and preventive tools against mpox among PWH are needed to better guide clinical decisions.


Asunto(s)
Infecciones por VIH , Mpox , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Antivirales , Recuento de Linfocito CD4 , Brotes de Enfermedades
10.
Epidemiology ; 33(6): 808-816, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35895578

RESUMEN

BACKGROUND: Population-level estimates of sexual network mixing for parameterizing prediction models of pre-exposure prophylaxis (PrEP) effectiveness are needed to inform prevention of HIV transmission among men who have sex with men (MSM). Estimates obtained by egocentric sampling are vulnerable to information bias due to incomplete respondent knowledge. METHODS: We estimated patterns of serosorting and PrEP sorting among MSM in the United States using data from a 2017-2019 egocentric sexual network study. Respondents served as proxies to report the HIV status and PrEP use of recent sexual partners. We contrasted results from a complete-case analysis (unknown HIV and PrEP excluded) versus a bias analysis with respondent-reported data stochastically reclassified to simulate unobserved self-reported data from sexual partners. RESULTS: We found strong evidence of preferential partnering across analytical approaches. The bias analysis showed concordance between sexual partners of HIV diagnosis and PrEP use statuses for MSM with diagnosed HIV (39%; 95% simulation interval: 31, 46), MSM who used PrEP (32%; 21, 37), and MSM who did not use PrEP (83%; 79, 87). The fraction of partners with diagnosed HIV was higher among MSM who used PrEP (11%; 9, 14) compared with MSM who did not use PrEP (4%; 3, 5). Comparatively, across all strata of respondents, the complete-case analysis overestimated the fractions of partners with diagnosed HIV or PrEP use. CONCLUSIONS: We found evidence consistent with HIV and PrEP sorting among MSM, which may decrease the population-level effectiveness of PrEP. Bias analyses can improve mixing estimates for parameterization of transmission models.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Seroclasificación por VIH , Homosexualidad Masculina , Humanos , Masculino , Profilaxis Pre-Exposición/métodos , Conducta Sexual , Parejas Sexuales , Estados Unidos/epidemiología
11.
AIDS Care ; 34(3): 284-293, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34369230

RESUMEN

Young Black men who have sex with men (YBMSM) bear a disproportionate burden of HIV, and HIV pre-exposure prophylaxis (PrEP) uptake has been slow. Decisions regarding PrEP initiation change in different life contexts over time. Our YBMSM cohort study found about 1/3 of those who initially declined PrEP subsequently changed and initiated PrEP care. This study explores the process of their PrEP decision changes. The study interviewed participants who initially voiced strong and clear reservations about PrEP, but subsequently started PrEP 1-14 months later. In "review/renew" follow-up interviews, participants reviewed their past statements from a time they declined PrEP, and renew their understanding regarding perspective and behavioral change. Analyzing the data with a positive deviance framework, we found that shifting the decisional balance in favor of PrEP initiation only required change in some areas. There were not consistent factors that prevented or facilitated PrEP uptake. Instead, YBMSM initiated PrEP while maintaining an array of substantial reservations. PrEP initiation discussions should be viewed by health practitioners as a longitudinal process, and routine PrEP offers should be made over time. To optimally facilitate PrEP use among YBMSM, the diverse benefits of PrEP should be emphasized rather than focusing on allaying all concerns.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Negro o Afroamericano , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino
12.
Clin Infect Dis ; 73(7): e2261-e2269, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32702116

RESUMEN

BACKGROUND: The US Centers for Disease Control and Prevention (CDC) recommends comprehensive sexually transmitted infection (STI) screening every 3-6 months for men who have sex with men (MSM) using human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). The gaps between these recommendations and clinical practice by region have not been quantified. METHODS: We used survey data collected from the internet-based ARTnet study between 2017 and 2019 on STI screening among MSM across the United States, stratified by current, prior, and never PrEP use. Poisson regression models with robust error variance were used to model factors, including residence in the Southeast, associated with consistent ("always" or "sometimes") exposure site-specific STI screening during PrEP care. RESULTS: Of 3259 HIV-negative MSM, 19% were currently using PrEP, 6% had used PrEP in the past, and 75% had never used PrEP. Among ever PrEP users, 87%, 78%, 57%, and 64% reported consistent screening for STIs by blood sample, urine sample or urethral swab, rectal swab, or pharyngeal swab, respectively, during PrEP care. Compared to PrEP users in all other regions, PrEP users in the Southeast were significantly less likely to be consistently screened for urogenital (adjusted prevalence ratio [aPR], 0.86; 95% confidence interval [CI], .76-.98) and rectal STIs (aPR, 0.76; 95% CI, .62-.93) during PrEP care. CONCLUSIONS: Substantial gaps exist between CDC recommendations for STI screening during PrEP care and current clinical practice, particularly for rectal and pharyngeal exposure sites that can harbor asymptomatic infections and for MSM in Southeast states where the STI burden is substantial.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/prevención & control , Estados Unidos
13.
J Antimicrob Chemother ; 76(9): 2368-2374, 2021 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-34007982

RESUMEN

BACKGROUND: HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat. METHODS: Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range. RESULTS: Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab,

Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Preparaciones Farmacéuticas , Fármacos Anti-VIH/uso terapéutico , Cobicistat/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Uretra
14.
Mem Cognit ; 49(6): 1137-1152, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33733434

RESUMEN

People recall and recognize animate words better than inanimate words, perhaps because memory systems were shaped by evolution to prioritize memory for predators, people, and food sources. Attentional paradigms show an animacy advantage that suggests that the animacy advantage in memory stems from a prioritization of animate items when allocating attentional resources during encoding. According to the attentional prioritization hypothesis, the animacy effect should be even larger when attention is divided during encoding. Alternatively, the animacy effect could be due to more controlled processing during encoding, and so should be reduced when attention is divided during encoding. We tested the attentional prioritization hypothesis and the controlled processing hypothesis by manipulating attention during encoding in free recall (Experiment 1) and recognition (Experiment 2) but failed to find interactions between word type and attentional load in either free recall or recognition, contrary to the predictions from both hypotheses. We then tested whether the semantic representations of animate and inanimate items differ in terms of number of semantic features, using existing recall data from an item-level megastudy by Lau, Goh, and Yap (Quarterly Journal of Experimental Psychology, 71 (10), 2207-2222, 2018). Animate items have more semantic features, which partially mediated the relationship between animacy status and recall.


Asunto(s)
Recuerdo Mental , Semántica , Atención , Humanos , Reconocimiento en Psicología , Asignación de Recursos
15.
Clin Infect Dis ; 71(3): 574-582, 2020 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-31499518

RESUMEN

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has great potential to reduce HIV incidence among young black men who have sex with men (YBMSM); however, initiation and persistence for this group remain low. We sought to understand the patterns and predictors of PrEP uptake and discontinuation among YBMSM in Atlanta, Georgia. METHODS: PrEP was offered to all participants in a prospective cohort of YBMSM aged 18-29 years not living with HIV. Time to PrEP uptake, first discontinuation, and final discontinuation were assessed using the Kaplan-Meier method. Cox proportional hazard models were used to identify predictors of uptake and discontinuation. RESULTS: After 440 person-years of follow-up, 44% of YBMSM initiated PrEP through the study after a median of 122 days. Of PrEP initiators, 69% had a first discontinuation and 40% had a final discontinuation during the study period. The median time to first PrEP discontinuation was 159 days. Factors associated with PrEP uptake included higher self-efficacy, sexually transmitted infection (STI), and condomless anal intercourse. Factors associated with discontinuation included younger age, cannabis use, STI, and fewer sex partners. HIV incidence was 5.23/100 person-years (95% confidence interval [CI], 3.40-7.23), with a lower rate among those who started PrEP (incidence rate ratio, 0.39; 95% CI, .16-.92). CONCLUSIONS: Persistent PrEP coverage in this cohort of YBMSM was suboptimal, and discontinuations were common despite additional support services available through the study. Interventions to support PrEP uptake and persistence, especially for younger and substance-using YBMSM, are necessary to achieve full PrEP effectiveness. CLINICAL TRIALS REGISTRATION: NCT02503618.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Adolescente , Adulto , Negro o Afroamericano , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Georgia/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Estudios Prospectivos , Adulto Joven
16.
AIDS Behav ; 24(7): 2054-2061, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31900813

RESUMEN

Many people living with HIV (PLWHIV) state that they would be willing to take significant risks to be "cured" of the virus. However, how they interpret the word "cure" in this context is not clear. We used a randomized survey to examine whether PLWHIV had a different willingness to take a hypothetical HIV medication if it causes flu-like symptoms, but provides: (a) cure, (b) remission that was labeled "cure", or (c) remission. PLWHIV (n = 454) were more willing to take a medication that provided a "cure" versus a "remission" if the side effects lasted less than 1 year. PLWHIV were more willing to take a medication that provided a remission that was labeled "cure" versus a "remission" (p = 0.01) if the side effects lasted 2 weeks. Clinicians and researchers should be aware of the impact of the word "cure" and ensure that PLWHIV fully understand the possible outcomes of their treatment options.


Asunto(s)
Toma de Decisiones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Pacientes/psicología , Investigadores/psicología , Quimioterapia/psicología , Femenino , Humanos , Intención , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
17.
Proc Natl Acad Sci U S A ; 114(50): E10755-E10762, 2017 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-29183982

RESUMEN

Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify candidate drug targets to specifically kill tumor cells, but this approach generally suffers from low consistency between screens. We found that many SS/L interactions involve essential genes and are therefore detectable within a limited range of knockdown efficiency. Such interactions are often missed by overly efficient RNAi reagents. We therefore developed an assay that measures viability over a range of knockdown efficiency within a cell population. This method, called Variable Dose Analysis (VDA), is highly sensitive to viability phenotypes and reproducibly detects SS/L interactions. We applied the VDA method to search for SS/L interactions with TSC1 and TSC2, the two tumor suppressors underlying tuberous sclerosis complex (TSC), and generated a SS/L network for TSC. Using this network, we identified four Food and Drug Administration-approved drugs that selectively affect viability of TSC-deficient cells, representing promising candidates for repurposing to treat TSC-related tumors.


Asunto(s)
Drosophila/genética , Ensayos de Selección de Medicamentos Antitumorales/métodos , Epistasis Genética , Genes Letales , Genes Supresores de Tumor , Interferencia de ARN , Animales , Proteínas de Drosophila/genética , Sistemas de Liberación de Medicamentos , Redes Reguladoras de Genes , Genes Esenciales , Humanos , Células Tumorales Cultivadas
18.
Sex Health ; 17(1): 91-95, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31610140

RESUMEN

Condoms are highly effective for HIV prevention, yet are not currently indicated by the US Food and Drug Administration (FDA) for anal sex. We surveyed a national sample of men who have sex with men to assess whether FDA label indication could affect anticipated condom use, and to determine levels of perceived condom failure for anal sex. We found that 69% of respondents anticipated that a label indication change would increase their likelihood of condom use. Median perceived failure was 15%. We anticipate that these results may aid the FDA in developing standards for a label indication for anal sex.


Asunto(s)
Condones/normas , Análisis de Falla de Equipo/estadística & datos numéricos , Guías como Asunto , Etiquetado de Productos/normas , Conducta Sexual , Adulto , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , United States Food and Drug Administration , Adulto Joven
19.
Behav Brain Sci ; 42: e291, 2020 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-31896384

RESUMEN

Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.


Asunto(s)
Enfermedad de Alzheimer , Memoria , Anciano , Cognición , Humanos , Trastornos de la Memoria , Recuerdo Mental
20.
Nurs Educ Perspect ; 41(2): 119-121, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31107394

RESUMEN

Virtual reality (VR) could enable clinical simulation centers to reach the teaching capacity of traditional hospital practica. This study quantitatively tests VR telepresence against two traditional simulation learning methods using a within-subject design and the Presence Questionnaire. Eight nursing students were randomly assigned and rotated through simulation participation, VR observation, and television observation conditions, completing a questionnaire after each condition. Each condition had a significant effect on presence. Simulation participation yielded the highest perceived presence, followed by VR, and lastly by television observation. This pilot study probed for effect and feedback that will inform a larger experiment.


Asunto(s)
Educación en Enfermería/métodos , Entrenamiento Simulado/métodos , Estudiantes de Enfermería/psicología , Realidad Virtual , Humanos , Investigación en Educación de Enfermería , Investigación en Evaluación de Enfermería , Proyectos Piloto
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