RESUMO
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.
Assuntos
Terapia Ocupacional , Humanos , Inquéritos e Questionários , AtitudeRESUMO
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.
Assuntos
Surtos de Doenças , Infecções por HIV/genética , Infecções por HIV/transmissão , HIV-1/genética , Alcaloides Opiáceos/efeitos adversos , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Busca de Comunicante , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Soropositividade para HIV , HIV-1/genética , Feminino , HIV-1/classificação , HIV-2/classificação , HIV-2/genética , Humanos , Masculino , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , RNA Viral , Sensibilidade e Especificidade , Fatores de TempoRESUMO
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.
Assuntos
Atitude do Pessoal de Saúde , Docentes , Terapeutas Ocupacionais , Terapia Ocupacional/educação , Recompensa , Acreditação , Comportamento Cooperativo , Humanos , Estudantes de Ciências da Saúde , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por Chlamydia/complicações , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vaginite por Trichomonas/complicações , Animais , Chlamydia trachomatis/isolamento & purificação , Coinfecção , Modelos Animais de Doenças , Feminino , Humanos , Macaca mulatta , Profilaxia Pré-Exposição , Vagina/microbiologia , Vagina/virologiaRESUMO
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.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Cicloexanos/administração & dosagem , Transmissão de Doença Infecciosa/prevenção & controle , Géis/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Tenofovir/administração & dosagem , Triazóis/administração & dosagem , Administração Tópica , Animais , Fármacos Anti-HIV/farmacocinética , Estudos Cross-Over , Cicloexanos/farmacocinética , Modelos Animais de Doenças , Macaca , Maraviroc , Placebos/administração & dosagem , Tenofovir/farmacocinética , Resultado do Tratamento , Triazóis/farmacocinéticaRESUMO
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.
Assuntos
Administração Intravaginal , HIV/efeitos dos fármacos , Inibidores da Transcriptase Reversa/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Tenofovir/administração & dosagem , Vagina/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Farmacorresistência Viral , Feminino , Géis , Infecções por HIV/virologia , Humanos , Macaca radiata , Profilaxia Pré-Exposição , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vagina/virologiaRESUMO
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.
Assuntos
Ciclo Menstrual , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/isolamento & purificação , Vagina/patologia , Vagina/virologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epitélio/patologia , Epitélio/virologia , Feminino , Macaca nemestrina , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/patologiaRESUMO
BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood. METHODS: Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy. RESULTS: Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤ .05, by the Wilcoxon test). CONCLUSIONS: C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological associations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.
Assuntos
Infecções por Chlamydia/complicações , Chlamydia trachomatis , Coinfecção/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Vaginite por Trichomonas/complicações , Trichomonas vaginalis , Animais , Colo do Útero/microbiologia , Colo do Útero/parasitologia , Colo do Útero/patologia , Colposcopia , Feminino , Macaca nemestrina , Fatores de Risco , Infecções Sexualmente Transmissíveis/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Síndrome de Imunodeficiência Adquirida dos Símios/virologiaRESUMO
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.
Assuntos
Pessoal Técnico de Saúde/educação , Comportamento Cooperativo , Modelos Educacionais , Terapia Ocupacional/educação , Preceptoria , Aprendizagem Baseada em Problemas , Ensino/métodos , Estágio Clínico , Currículo , Atenção à Saúde , Docentes , Humanos , Estudantes de Ciências da SaúdeRESUMO
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.
Assuntos
Docentes , Pessoal de Saúde , Terapia Ocupacional/educação , Papel Profissional , Humanos , Inquéritos e Questionários , Carga de TrabalhoRESUMO
Daily preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a novel strategy for preventing human immunodeficiency virus infection. We investigated in macaques whether FTC/TDF prevents transmission of a tenofovir-resistant simian/human immunodeficiency virus (SHIV) containing the K65R mutation. Six macaques received weekly a dose of FTC/TDF 3 days before rectal SHIV exposures and a second dose 2 hours after. Six untreated animals were controls. Animals were exposed rectally to escalating virus doses weekly for up to 28 weeks. PrEP significantly delayed infection with SHIVK65R (P = .028), although 4 of 6 FTC/TDF-treated macaques were infected at the end of the challenges. These findings highlight the need to closely monitor PrEP efficacy in areas with prevalent K65R.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Desoxicitidina/análogos & derivados , Farmacorresistência Viral , HIV/efeitos dos fármacos , Organofosfonatos/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Adenina/administração & dosagem , Administração Oral , Animais , Desoxicitidina/administração & dosagem , Transmissão de Doença Infecciosa/prevenção & controle , Emtricitabina , HIV/genética , Macaca , Mutação de Sentido Incorreto , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Tenofovir , Resultado do TratamentoRESUMO
A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , Organofosfonatos/administração & dosagem , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vagina/efeitos dos fármacos , Cremes, Espumas e Géis Vaginais/administração & dosagem , Adenina/administração & dosagem , Adenina/química , Animais , Fármacos Anti-HIV/química , Células Cultivadas , Estabilidade de Medicamentos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Meia-Vida , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Organofosfonatos/química , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Tenofovir , Vagina/imunologia , Vagina/virologia , Cremes, Espumas e Géis Vaginais/químicaRESUMO
BACKGROUND: The impact of pre-exposure prophylaxis (PrEP) with antiretrovirals on breakthrough HIV or SHIV infection is not fully documented. We addressed the hypothesis that SHIV(SF162P3) infection despite active PrEP results in altered early immune parameters, compared with untreated infection. METHODS: Eleven rhesus macaques were infected during repeated, rectal, low-dose SHIV(SF162P3) exposures while receiving concurrent oral PrEP (Truvada [n = 2] or GS7340 [n = 4]) or as untreated controls (n = 5). We measured SHIV RNA, inflammatory cytokines, CD4 cells, and SHIV-specific and memory T cells until 20 weeks after peak viremia. RESULTS: SHIV infection during PrEP resulted in 100-fold lower peak viremia and lower IL-15, IL-18, and IL-1Ra levels, compared with controls (P < .05; Wilcoxon rank-sum test). Unlike controls, PrEP-treated macaques showed no significant CD4 cell count reduction during acute infection and developed more SHIV-specific central memory T cells, relative to controls. After in vivo CD8 cell depletion, viral load increased to similar levels, indicating that CD8 cells were critical for viral control in both groups. CONCLUSIONS: PrEP with antiretrovirals has beneficial effects on early SHIV infection even when infection is not prevented. Although long-term immune control could not be examined in this SHIV infection model, our results suggest that PrEP results in improved early disease parameters in breakthrough infections.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/farmacologia , Linfócitos T CD4-Positivos/imunologia , Desoxicitidina/análogos & derivados , Compostos Organofosforados/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Adenina/farmacologia , Alanina , Animais , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/virologia , Citocinas/sangue , Citocinas/imunologia , Desoxicitidina/farmacologia , Combinação de Medicamentos , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila , Estudos Longitudinais , Macaca mulatta , Masculino , RNA Viral/química , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Estatísticas não Paramétricas , Tenofovir/análogos & derivados , Viremia/imunologia , Viremia/virologiaRESUMO
BACKGROUND: Zoonotic transmission of simian retroviruses in Central Africa is ongoing and can result in pandemic human infection. While simian foamy virus (SFV) infection was reported in primate hunters in Cameroon and Gabon, little is known about the distribution of SFV in Africa and whether human-to-human transmission and disease occur. We screened 3,334 plasmas from persons living in rural villages in central Democratic Republic of Congo (DRC) using SFV-specific EIA and Western blot (WB) tests. PCR amplification of SFV polymerase sequences from DNA extracted from buffy coats was used to measure proviral loads. Phylogenetic analysis was used to define the NHP species origin of SFV. Participants completed questionnaires to capture NHP exposure information. RESULTS: Sixteen (0.5%) samples were WB-positive; 12 of 16 were from women (75%, 95% confidence limits 47.6%, 92.7%). Sequence analysis detected SFV in three women originating from Angolan colobus or red-tailed monkeys; both monkeys are hunted frequently in DRC. NHP exposure varied and infected women lived in distant villages suggesting a wide and potentially diverse distribution of SFV infections across DRC. Plasmas from 22 contacts of 8 WB-positive participants were all WB negative suggesting no secondary viral transmission. Proviral loads in the three women ranged from 14 - 1,755 copies/105 cells. CONCLUSIONS: Our study documents SFV infection in rural DRC for the first time and identifies infections with novel SFV variants from Colobus and red-tailed monkeys. Unlike previous studies, women were not at lower risk for SFV infection in our population, providing opportunities for spread of SFV both horizontally and vertically. However, limited testing of close contacts of WB-positive persons did not identify human-to-human transmission. Combined with the broad behavioral risk and distribution of NHPs across DRC, our results suggest that SFV infection may have a wider geographic distribution within DRC. These results also reinforce the potential for an increased SFV prevalence throughout the forested regions of Africa where humans and simians co-exist. Our finding of endemic foci of SFV infection in DRC will facilitate longitudinal studies to determine the potential for person-to-person transmissibility and pathogenicity of these zoonotic retroviral infections.
Assuntos
Doenças dos Macacos/transmissão , Infecções por Retroviridae/transmissão , Vírus Espumoso dos Símios/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Colobus , Congo , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Filogenia , Vírus Espumoso dos Símios/classificação , Vírus Espumoso dos Símios/genética , Carga Viral , Zoonoses/transmissãoRESUMO
Recent-infection testing assays/algorithms (RITAs) have been developed to exploit the titer and avidity of HIV antibody evolution following seroconversion for incidence estimation. The Vitros Anti-HIV 1+2 assay (Ortho-Clinical Diagnostics) was approved by the FDA to detect HIV-1 and HIV-2 infections. We developed a less-sensitive (LS) and an avidity-modified version of this assay to detect recent HIV infection. Seroconversion panels (80 subjects, 416 samples) were tested to calculate the mean duration of recent infection (MDR) for these assays. A panel from known long-term (2+ years) HIV-infected subjects on highly active antiretroviral therapy (HAART) (n = 134) and subjects with low CD4 counts (AIDS patients [n = 140]) was used to measure the false-recent rate (FRR) of the assays. Using a signal-to-cutoff ratio of 20 and the LS-Vitros assay gave a RITA MDR of 215 days (95% confidence interval [95% CI], ± 65 days) and using an avidity index (AI) of 0.6 gave an MDR of 170 days (± 44 days), while a combination of the two assays yielded a MDR of 146 days (± 38.6) and an FRR of 8%. Misclassifying subjects with known long-term infection as recently infected occurred in 14% of AIDS patients and 29% (95% CI, 22, 38) of HAART subjects and 3% (95% CI, 0.8, 7.2) and 42% (95% CI, 33, 51), respectively, for the LS- and avidity-modified Vitros assays, with a misclassification rate of 15% (95% CI, 11, 20) overall using a dual-assay algorithm. Both modified Vitros assays can be used to estimate the length of time since seroconversion and in calculations for HIV incidence. Like other RITAs, they are subject to high FRR in subjects on HAART or with AIDS.
Assuntos
Afinidade de Anticorpos , Anticorpos Anti-HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/imunologia , Humanos , Incidência , Sensibilidade e EspecificidadeRESUMO
Daily preexposure prophylaxis (PrEP) with Truvada (emtricitabine [FTC] and tenofovir disoproxil fumarate [TDF]) is a novel HIV prevention strategy recently found to reduce HIV incidence among men who have sex with men. We used a macaque model of HIV transmission to investigate if Truvada maintains prophylactic efficacy against an FTC-resistant isolate containing the M184V mutation. Five macaques received a dose of Truvada 3 days before exposing them rectally to the simian/human immunodeficiency virus mutant SHIV162p3(M184V), followed by a second dose 2 h after exposure. Five untreated animals were used as controls. Virus exposures were done weekly for up to 14 weeks. Despite the high (>100-fold) level of FTC resistance conferred by M184V, all five treated animals were protected from infection, while the five untreated macaques were infected (P = 0.0008). Our results show that Truvada maintains high prophylactic efficacy against an FTC-resistant isolate. Increased susceptibility to tenofovir due to M184V and other factors, including residual antiviral activity by FTC and/or reduced virus fitness due to M184V, may all have contributed to the observed protection.
Assuntos
Antivirais/farmacologia , Desoxicitidina/análogos & derivados , HIV/efeitos dos fármacos , Mutação , Compostos Organofosforados/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Animais , Linhagem Celular , Desoxicitidina/farmacologia , Combinação de Medicamentos , Farmacorresistência Viral , Emtricitabina , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila , HIV/genética , Humanos , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/genéticaRESUMO
Preexposure prophylaxis (PrEP) with antiretroviral drugs is a novel human immunodeficiency virus (HIV) prevention strategy. It is generally thought that high systemic and mucosal drug levels are sufficient for protection. We investigated whether GS7340, a next-generation tenofovir (TFV) prodrug that effectively delivers tenofovir diphosphate (TFV-DP) to lymphoid cells and tissues, could protect macaques against repeated weekly rectal simian-human immunodeficiency virus (SHIV) exposures. Macaques received prophylactic GS7340 treatment 3 days prior to each virus exposure. At 3 days postdosing, TFV-DP concentrations in peripheral blood mononuclear cells (PBMCs) were about 50-fold higher than those seen with TFV disoproxil fumarate (TDF), and they remained above 1,000 fmol/10(6) cells for as long as 7 days. TFV-DP accumulated in lymphoid and rectal tissues, with concentrations at 3 days exceeding 500 fmol/10(6) mononuclear cells. Despite high mucosal and systemic TFV levels, GS7340 was not protective. Since TFV-DP blocks reverse transcription by competing with the natural dATP substrate, we measured dATP contents in peripheral lymphocytes, lymphoid tissue, and rectal mononuclear cells. Compared to those in circulating lymphocytes and lymphoid tissue, rectal lymphocytes had 100-fold higher dATP concentrations and dATP/TFV-DP ratios, likely reflecting the activated status of the cells and suggesting that TFV-DP may be less active at the rectal mucosa. Our results identify dATP/TFV-DP ratios as a possible correlate of protection by TFV and suggest that natural substrate concentrations at the mucosa will likely modulate the prophylactic efficacy of nucleotide reverse transcriptase inhibitors.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Nucleotídeos de Desoxiadenina/metabolismo , Infecções por HIV/prevenção & controle , Organofosfonatos/uso terapêutico , Pró-Fármacos/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Adenina/administração & dosagem , Adenina/farmacocinética , Adenina/uso terapêutico , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Quimioprevenção , Infecções por HIV/virologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Humanos , Linfócitos/metabolismo , Tecido Linfoide/metabolismo , Macaca , Organofosfonatos/administração & dosagem , Organofosfonatos/farmacocinética , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacocinética , Reto/virologia , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/farmacocinética , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Especificidade por Substrato , TenofovirRESUMO
BACKGROUND: Among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) taking combination antiretroviral therapy (cART), the impact of rectal sexually transmitted infections (STIs) on rectal HIV-1 shedding is unknown. METHODS: Human immunodeficiency virus type 1 (HIV-1) RNA was quantified from rectal swabs collected for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) screening of HIV-1-infected MSM. Correlations of STIs with rectal viral load were explored using multinomial regression modeling. HIV-1 coreceptor tropism was predicted from sequencing in a subset of men. RESULTS: Thirty-one (39%) of 80 men (59 prescribed combination antiretroviral therapy [cART]) had HIV detected in 38 (42%) of 91 rectal swabs. Rectal HIV detection was associated with plasma virus loads above 3.15 log10 copies/mL (95% confidence limit [CL] 2.73, 3.55) and paired rectal viral loads and plasma viral loads were correlated (Kendall's tau [τ] 0.68, Spearman rho [P] = .77). Rectal STIs and abnormal anal cytology were not associated with rectal viral load. HIV coreceptor distribution was very similar between the plasma and rectum in 3 of 4 men. CONCLUSIONS: Plasma and rectal viral load were correlated, and rectal STIs did not increase the likelihood of detecting HIV in the rectal secretions in MSM, including those with low or undetectable plasma viral load. Suppressing plasma viral load is likely to reduce risk of HIV transmission to insertive partners.
Assuntos
Infecções por Chlamydia/complicações , Chlamydia trachomatis , Gonorreia/complicações , Infecções por HIV/virologia , HIV-1 , Neisseria gonorrhoeae , RNA Viral/análise , Reto/virologia , Adulto , Antirretrovirais/farmacologia , Doenças do Ânus/patologia , Doenças do Ânus/virologia , Contagem de Linfócito CD4 , Quimioterapia Combinada , Infecções por HIV/complicações , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Receptores CCR5/análise , Receptores CCR5/sangue , Receptores CXCR4/análise , Receptores CXCR4/sangue , Reto/química , Análise de Regressão , Carga Viral/efeitos dos fármacosRESUMO
The Aptima HIV-1 RNA qualitative assay tested with a WHO-approved HIV type 1 RNA standard in 16- and 32-member pools detected 100% of the pools (1,070 and 2,130 HIV-1 RNA copies/ml/pool, respectively), thus exceeding the FDA-required lower limit of detection. The Aptima test can be used to screen for acute-phase HIV infection.