RESUMEN
Collaborative supervision is not new to occupational therapy; however, its use remains limited. To identify factors affecting the perceived value and use of collaborative supervision, a survey was developed and disseminated to fieldwork educators seeking their opinions and experiences. The survey had 382 respondents. Familiarity with constructs and prior experience using this collaborative supervision seem to be the highest predictor of use. Understanding the impact of practitioner attributes on the perceived value of collaborative fieldwork can help expand the use of collaborative fieldwork supervision.
Asunto(s)
Terapia Ocupacional , Humanos , Encuestas y Cuestionarios , ActitudRESUMEN
BACKGROUND: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies. METHODS: Plasma samples (n = 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. In addition, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak. RESULTS: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, and 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, and 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015. CONCLUSIONS: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions.
Asunto(s)
Anticuerpos Anti-VIH/inmunología , Antígenos VIH/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , Proteínas gp160 de Envoltorio del VIH/inmunología , Infecciones por VIH/epidemiología , Algoritmos , Proteína gp41 de Envoltorio del VIH/inmunología , Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Seropositividad para VIH/epidemiología , VIH-1/inmunología , Humanos , Indiana/epidemiología , Sensibilidad y Especificidad , Seroconversión/fisiologíaRESUMEN
In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID) was recognized in rural Indiana. By September 2016, 205 persons in this community of approximately 4400 had received a diagnosis of HIV infection. We report results of new approaches to analyzing epidemiologic and laboratory data to understand transmission during this outbreak. HIV genetic distances were calculated using the polymerase region. Networks were generated using data about reported high-risk contacts, viral genetic similarity, and their most parsimonious combinations. Sample collection dates and recency assay results were used to infer dates of infection. Epidemiologic and laboratory data each generated large and dense networks. Integration of these data revealed subgroups with epidemiologic and genetic commonalities, one of which appeared to contain the earliest infections. Predicted infection dates suggest that transmission began in 2011, underwent explosive growth in mid-2014, and slowed after the declaration of a public health emergency. Results from this phylodynamic analysis suggest that the majority of infections had likely already occurred when the investigation began and that early transmission may have been associated with sexual activity and injection drug use. Early and sustained efforts are needed to detect infections and prevent or interrupt rapid transmission within networks of uninfected PWID.
Asunto(s)
Brotes de Enfermedades , Infecciones por VIH/genética , Infecciones por VIH/transmisión , VIH-1/genética , Alcaloides Opiáceos/efectos adversos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Trazado de Contacto , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Conducta Sexual , Estados Unidos/epidemiologíaRESUMEN
The availability of reliable laboratory methods for determining recent HIV infection is vital for accurate estimation of population-based incidence. The mean duration of recent infection (MDRI) and false recent rate (FRR) are critical parameters for HIV incidence assays, as they impact HIV incidence estimates and provide a measure of assay performance. The HIV-1 Multiplex assay is an in-house developed, magnetic bead-based assay that measures virus-specific antibody levels and avidity to multiple analytes. To ensure quality control and to facilitate transfer of the assay to external laboratories or testing facilities, the in-house assay has been adapted and produced in kit form. Here, we describe the performance characteristics of the multiplex kit and demonstrate the stability of the kit components over a one-year period. Two statistical methods were employed to estimate the MDRI of the individual analytes and five different algorithms, combining multiple analyte values. The MDRI estimates for the individual analytes and five algorithms were all between 200 and 300 days post-seroconversion, with no notable difference between the two statistical approaches. All five algorithms exhibited a 0% FRR with specimens from long-term, subtype B HIV-1-infected individuals. The assay parameters described in this study provide the necessary tools to implement the HIV-1 multiplex assay and improves the utility of the assay for field use.
Asunto(s)
Serodiagnóstico del SIDA/instrumentación , Anticuerpos Anti-VIH/análisis , Infecciones por VIH/diagnóstico , VIH-1/inmunología , Algoritmos , HumanosRESUMEN
The purpose of this national survey was to explore perceptions of professional reward among occupational therapist (OT) and occupational therapy assistant (OTA) academic fieldwork coordinators (AFWCs). Agreement was found in ranking the value of six role factors: (1) fieldwork data management, (2) fieldwork site management, (3) fieldwork teaching and consultation, (4) departmental and institutional compliance, (5) scholarship and accreditation, and (6) laying groundwork for students in fieldwork. Both levels of AFWC indicated teaching and consultation had the highest value and data management the least. OT AFWCs placed significantly higher value on publishing articles and lower value on educating fieldwork educators about role delineation than OTA AFWCs. Five themes emerged regarding professional reward: (1) intrinsic reward, (2) collaboration, (3) development of the profession, (4) feeling appreciated, and (5) student success. AFWCs value activities involving personal interaction, promoting professional development, and facilitating student success. Results have implications for AFWC collaboration, workload distribution, and scholarship.
Asunto(s)
Actitud del Personal de Salud , Docentes , Terapeutas Ocupacionales , Terapia Ocupacional/educación , Recompensa , Acreditación , Conducta Cooperativa , Humanos , Estudiantes del Área de la Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. METHODS: Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30âmin or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30âmin or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (nâ=â4) and uninfected (nâ=â4) macaques. RESULTS: Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30âmin before SHIV challenge (Pâ<â0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (Pâ=â0.07). Plasma TFV and TFV diphosphate concentrations in tissues and vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. CONCLUSION: Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por Chlamydia/complicaciones , Coinfección/complicaciones , Transmisión de Enfermedad Infecciosa/prevención & control , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Tenofovir/administración & dosificación , Vaginitis por Trichomonas/complicaciones , Administración Tópica , Animales , Fármacos Anti-VIH/análisis , Fármacos Anti-VIH/farmacocinética , Femenino , Macaca , Placebos/administración & dosificación , Plasma/química , Tenofovir/análisis , Tenofovir/farmacocinética , Vagina/química , Cremas, Espumas y Geles Vaginales/administración & dosificaciónRESUMEN
HIV-1 and HSV-2 are frequent genital co-infections in women. To determine how self-collected genital swabs compare to provider-collected cervicovaginal lavage, paired self-collected genital swabs and cervicovaginal lavage from women co-infected with HIV-1 and HSV-2 were evaluated. Women were in an acyclovir clinical trial and their samples were tested for HIV-1 RNA (361 samples) and HSV-2 DNA (378 samples). Virus shedding, quantity and acyclovir effect were compared. HIV-1 and HSV-2 were more frequently detected in self-collected genital swabs: 74.5% of self-collected genital swabs and 63.6% of cervicovaginal lavage had detectable HIV-1 (p ≤ 0.001, Fisher's exact test) and 29.7% of self-collected genital swabs and 19.3% of cervicovaginal lavage had detectable HSV-2 (p ≤ 0.001) in the placebo month. Cervicovaginal lavage and self-collected genital swabs virus levels were correlated (Spearman's rho, 0.68 for HIV; 0.61 for HSV-2) and self-collected genital swabs levels were generally higher. In multivariate modeling, self-collected genital swabs and cervicovaginal lavage could equally detect the virus-suppressive effect of acyclovir: for HIV-1, proportional odds ratios were 0.42 and 0.47 and for HSV-2, they were 0.10 and 0.03 for self-collected genital swabs and cervicovaginal lavage, respectively. Self-collected genital swabs should be considered for detection and measurement of HIV-1 and HSV-2 in clinical trials and other studies as they are a sensitive method to detect virus and can be collected in the home with frequent sampling.
Asunto(s)
Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Herpes Genital/tratamiento farmacológico , Herpesvirus Humano 2/efectos de los fármacos , Antirretrovirales , Coinfección , Femenino , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/genética , VIH-1/aislamiento & purificación , VIH-1/fisiología , Herpes Genital/transmisión , Herpes Genital/virología , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/aislamiento & purificación , Herpesvirus Humano 2/fisiología , Humanos , Estudios Retrospectivos , Tailandia/epidemiología , Irrigación Terapéutica , Carga Viral , Esparcimiento de Virus/efectos de los fármacosRESUMEN
BACKGROUND: Understanding the period of time between an exposure resulting in infection with human immunodeficiency virus (HIV) and when a test can reliably detect the presence of that infection, that is, the test window period, may benefit testing programs and clinicians in counseling patients about when the clinician and the patient can be confident a suspected exposure did not result in HIV infection. METHODS: We evaluated the intervals between reactivity of the Aptima HIV-1 RNA test (Aptima) and 20 US Food and Drug Administration-approved HIV immunoassays using 222 longitudinally collected plasma specimens from HIV-1 seroconverters from the United States. Using interval-censored survival and binomial regression approaches a multi-model framework was implemented to estimate the relative emergence of test reactivity, referred to here as an inter-test reactivity interval (ITRI). We then combined ITRI results with simulated data for the eclipse period, the time between exposure and detection of HIV virus by Aptima, to estimate the window period for each test. RESULTS: The estimated ITRIs were shorter with each new class of HIV tests, ranging from 5.9 to 24.8 days. The 99th percentiles of the window period probability distribution ranged from 44 days for laboratory screening tests that detect both antigen and antibody to 65 days for the Western blot test. CONCLUSIONS: Our directly comparable estimates of the emergence of reactivity for 20 immunoassays are valuable to testing providers for interpreting negative HIV test results obtained shortly after exposure, and for counseling individuals on when to retest after an exposure.
Asunto(s)
Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , Seropositividad para VIH , VIH-1/genética , Femenino , VIH-1/clasificación , VIH-2/clasificación , VIH-2/genética , Humanos , Masculino , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , ARN Viral , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
The application of biomarkers for 'recent' infection in cross-sectional HIV incidence surveillance requires the estimation of critical biomarker characteristics. Various approaches have been employed for using longitudinal data to estimate the Mean Duration of Recent Infection (MDRI) - the average time in the 'recent' state. In this systematic benchmarking of MDRI estimation approaches, a simulation platform was used to measure accuracy and precision of over twenty approaches, in thirty scenarios capturing various study designs, subject behaviors and test dynamics that may be encountered in practice. Results highlight that assuming a single continuous sojourn in the 'recent' state can produce substantial bias. Simple interpolation provides useful MDRI estimates provided subjects are tested at regular intervals. Regression performs the best - while 'random effects' describe the subject-clustering in the data, regression models without random effects proved easy to implement, stable, and of similar accuracy in scenarios considered; robustness to parametric assumptions was improved by regressing 'recent'/'non-recent' classifications rather than continuous biomarker readings. All approaches were vulnerable to incorrect assumptions about subjects' (unobserved) infection times. Results provided show the relationships between MDRI estimation performance and the number of subjects, inter-visit intervals, missed visits, loss to follow-up, and aspects of biomarker signal and noise.
RESUMEN
INTRODUCTION: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). METHODS: Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. RESULTS: It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). CONCLUSIONS: SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.
Asunto(s)
Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/farmacología , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Vagina/virología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Macaca nemestrina , Síndrome de Inmunodeficiencia Adquirida del Simio/virologíaRESUMEN
HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States.
Asunto(s)
Biomarcadores/análisis , Antígenos VIH/inmunología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , VIH-1/inmunología , Serodiagnóstico del SIDA , Afinidad de Anticuerpos , Ensayos Clínicos como Asunto , Estudios de Seguimiento , Infecciones por VIH/clasificación , Infecciones por VIH/inmunología , Seropositividad para VIH , VIH-1/aislamiento & purificación , Humanos , Técnicas para Inmunoenzimas , Incidencia , Estudios Longitudinales , Pronóstico , Pruebas Serológicas , Factores de Tiempo , Estados Unidos/epidemiología , Carga ViralRESUMEN
Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally. All animals in the placebo group were infected with SHIV, while 4 of 6 PrEP recipients remained uninfected (P= .03). Oral FTC/TDF maintains efficacy in a macaque model of sexually transmitted coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por Chlamydia/complicaciones , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/uso terapéutico , Infecciones por VIH/prevención & control , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Vaginitis por Trichomonas/complicaciones , Animales , Chlamydia trachomatis/aislamiento & purificación , Coinfección , Modelos Animales de Enfermedad , Femenino , Humanos , Macaca mulatta , Profilaxis Pre-Exposición , Vagina/microbiología , Vagina/virologíaRESUMEN
We describe HIV-1 evolutionary dynamics in the 4 participants from the TDF2-PrEP trial who became HIV-1 infected while prescribed emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). At seroconversion, virus diversity in the 2 participants with detectable drug was only 0.05% (95% confidence intervals: 0.04 to 0.06) and 0.07% (0.06 to 0.08) compared with 2.25% (1.95 to 2.6) and 0.42% (0.36 to 0.49) in those with no detectable drug and 0.07%-0.69% in 5 placebo recipients (P > 0.5). At 10 months, diversity in adherent participants was only 0.37% (0.31 to 0.41) and 0.86% (0.82 to 0.90) compared with 0.5%-1.7% among participants who did not take FTC/TDF (P > 0.5). Although limited by the small number of infections that reduced the power to detect differences, we found that sequences from seroconverters with detectable drug were more homogeneous than those from placebo or nonadherent seroconverters.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Profilaxis Pre-Exposición , Tenofovir/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Botswana , Recuento de Linfocito CD4 , Método Doble Ciego , Evolución Molecular , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/genética , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. METHODS: Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. RESULTS: In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P < 0.05, linear regression analysis), but not nucleated layer thinning (Pearson r = 0.6, P = 0.15). CONCLUSIONS: These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.
Asunto(s)
Ciclo Menstrual , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Vagina/patología , Vagina/virología , Animales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Epitelio/patología , Epitelio/virología , Femenino , Macaca nemestrina , Masculino , Síndrome de Inmunodeficiencia Adquirida del Simio/patologíaRESUMEN
BACKGROUND: Topically delivered tenofovir (TFV) from intravaginal rings, tablets, or gels is being evaluated for HIV prevention. We previously demonstrated that TFV delivered vaginally by gel protected macaques from vaginal infection with SHIV. Here we investigated efficacy of the TFV gel against vaginal transmission of a TFV-resistant SHIV containing the K65R mutation (SHIV162P3K65R) and its relationship to drug levels in vaginal tissues. RESULTS: SHIV162P3K65R shows approximately a 5-fold reduction in susceptibility to TFV compared to wild-type SHIV. Efficacy was evaluated in pig-tailed macaques exposed vaginally twice-weekly (up to 10 weeks) to SHIV162P3K65R 30 min after receiving placebo (n = 6) or 1% TFV (n = 6) gel. Four of the six controls were infected after a median of 5 exposures. In contrast, five of six macaques that received TFV gel remained uninfected after 20 vaginal SHIV162P3K65R exposures, resulting in an estimated efficacy of 75%. The mean intracellular TFV-diphosphate (TFV-DP) concentrations in vaginal lymphocytes 4 h after a single gel dose were found to be high (1,631 fmol/10(6) cells, range 492-3,847) and within the in vitro IC75 range (1,206 fmol/10(6) cells) for SHIV162P3K65R. CONCLUSION: Both the modest resistance conferred by K65R and the high TFV-DP exposure in vaginal lymphocytes, likely explain the observed protection. The findings in this model do not predict complete loss of protection by topical TFV against vaginal exposure to HIV-1K65R viruses and provide a tissue drug target for high efficacy. These data will facilitate the development of TFV delivery platforms that have high activity on both wild-type and TFV-resistant viruses.
Asunto(s)
Administración Intravaginal , VIH/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Tenofovir/administración & dosificación , Vagina/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Farmacorresistencia Viral , Femenino , Geles , Infecciones por VIH/virología , Humanos , Macaca radiata , Profilaxis Pre-Exposición , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/genética , Vagina/virologíaRESUMEN
BACKGROUND: Rectal human immunodeficiency virus (HIV) transmission is an important driver of the HIV epidemic. Optimally formulated gels of antiretroviral drugs are under development for preventing rectally acquired HIV. We investigated in a macaque model the pharmacokinetics and efficacy of 3 rectal gel formulations METHODS: Single-dose pharmacokinetics of low-osmolar 1% maraviroc (MVC), 1% tenofovir (TFV), or 1% MVC/1% TFV combination gel were evaluated in blood, rectal fluids, colorectal biopsy specimens, and rectal lymphocytes. Efficacy was evaluated over 10 twice-weekly rectal SHIV162p3 challenges in rhesus macaques that received either placebo (n = 7), MVC (n = 6), TFV (n = 6), or MVC/TFV (n = 6) gel 30 minutes before each challenge. RESULTS: MVC and TFV were detected in plasma 30 minutes after gel application and remained above 95% inhibitory concentrations in rectal fluids at 24 hours. MVC, TFV, and TFV diphosphate (TFV-DP) concentrations in colorectal tissues collected up to 30 cm from the anal margin were all high at 2 hours, demonstrating rapid and extended tissue dosing. TFV-DP concentrations in tissue homogenates and rectal lymphocytes were highly correlated (r(2) = 0.82). All 3 gel formulations were highly protective (82% efficacy; P ≤ .02 by the log-rank test). CONCLUSIONS: Desirable pharmacokinetic profiles and high efficacy in this macaque model support the clinical development of these gel formulations for preventing rectal HIV infection.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Ciclohexanos/administración & dosificación , Transmisión de Enfermedad Infecciosa/prevención & control , Geles/administración & dosificación , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Tenofovir/administración & dosificación , Triazoles/administración & dosificación , Administración Tópica , Animales , Fármacos Anti-VIH/farmacocinética , Estudios Cruzados , Ciclohexanos/farmacocinética , Modelos Animales de Enfermedad , Macaca , Maraviroc , Placebos/administración & dosificación , Tenofovir/farmacocinética , Resultado del Tratamiento , Triazoles/farmacocinéticaRESUMEN
BACKGROUND: Preexposure prophylaxis (PrEP) for HIV prevention is a novel biomedical prevention method. We have previously modeled PrEP during rectal SHIV exposures in macaques and identified that Simian/Human Immunodeficiency Virus chimera (SHIV)-specific T-cell responses were induced in the presence of antiretroviral drugs, an observation previously termed T-cell chemo-vaccination. This report expands those initial findings by examining a larger group of macaques that were given oral or topical PrEP during repeated vaginal virus exposure. METHODS: Thirty-six female pigtail macaques received up to 20 repeat low-dose vaginal inoculations with wild-type (WT) SHIVSF162P3 (n = 24) or a clonal derivative with the tenofovir (TFV) K65R drug-resistant mutation (n = 12). PrEP consisted of oral Truvada (n = 6, WT), TFV vaginal gel (n = 6, K65R), or TFV intravaginal ring (n = 6, WT). The remaining animals were PrEP-inexperienced controls (n = 12, WT; n = 6, K65R). SHIV-specific T cells were identified and characterized using interferon γ Enzyme-Linked ImmunoSpot (ELISPOT) and multiparameter flow cytometry. RESULTS: Of 9 animals that were on PrEP and remained uninfected during WT SHIV vaginal challenges, 8 (88.9%) developed virus-specific T-cell responses. T cells were in CD4 and CD8 compartments, reached up to 4900 interferon γ-producing cells per million peripheral blood mononuclear cells, and primarily pol directed. In contrast, the replication-impaired K65R virus did not induce detectable T-cell responses, likely reflecting the need for adequate replication. CONCLUSIONS: Virus-specific T-cell responses occur frequently in oral or topical PrEP-protected pigtail macaques after vaginal exposure to WT SHIV virus. The contribution of such immune responses to protection from infection during and after PrEP warrants further investigation.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Desoxicitidina/análogos & derivados , Infecciones por VIH/prevención & control , Macaca nemestrina , Compuestos Organofosforados , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Linfocitos T/fisiología , Administración Oral , Administración Tópica , Animales , Combinación de Medicamentos , Farmacorresistencia Viral , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil , Femenino , Profilaxis Pre-Exposición , Virus Reordenados/efectos de los fármacos , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Virus de la Inmunodeficiencia de los Simios/inmunologíaRESUMEN
A nation-wide survey was conducted of occupational therapy and occupational therapy assistant academic fieldwork coordinators (AFWCs) to describe demographic characteristics and tasks of the role. From the data, 10 clusters of role tasks of the AFWC are described. AFWCs view the position as a final career goal although the majority of respondents reported 5 years or less experience. Administrative assistant support and hours dedicated to fieldwork tasks are higher at the professional level than for occupational therapy assistant AFWCs. AFWCs reported difficulty accomplishing tasks in a 40-h work week and limited time for research and scholarship. Recommendations are provided for recruitment and retention through development of a systematic training program and establishment of a national fieldwork education research agenda.
Asunto(s)
Docentes , Personal de Salud , Terapia Ocupacional/educación , Rol Profesional , Humanos , Encuestas y Cuestionarios , Carga de TrabajoRESUMEN
Historically, occupational therapists have used a traditional one-to-one approach to supervision on fieldwork. Due to the impact of managed care on health-care delivery systems, a dramatic increase in the number of students needing fieldwork placement, and the advantages of group learning, the collaborative supervision model has evolved as a strong alternative to an apprenticeship supervision approach. This article builds on the available research to address barriers to model use, applying theoretical foundations of collaborative supervision to practical considerations for academic fieldwork coordinators and fieldwork educators as they prepare for participation in group supervision of occupational therapy and occupational therapy assistant students on level II fieldwork.
Asunto(s)
Técnicos Medios en Salud/educación , Conducta Cooperativa , Modelos Educacionales , Terapia Ocupacional/educación , Preceptoría , Aprendizaje Basado en Problemas , Enseñanza/métodos , Prácticas Clínicas , Curriculum , Atención a la Salud , Docentes , Humanos , Estudiantes del Área de la SaludRESUMEN
α4ß7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4ß7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4ß7 reduces mucosal transmission of SIV in macaques.