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1.
Clin Infect Dis ; 78(3): 651-654, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-37590957

RESUMO

Human immunodeficiency virus (HIV)-associated immunosuppression may increase the risk of hospitalization with mpox. Among persons diagnosed with mpox in the state of Georgia, we characterized the association between hospitalization with mpox and HIV status. People with HIV and a CD4 count <350 cells/mm3 or who were not engaged in HIV care had an increased risk of hospitalization.


Assuntos
Infecções por HIV , Mpox , Humanos , Contagem de Linfócito CD4 , Georgia/epidemiologia , Hospitalização , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia
2.
J Med Primatol ; 53(4): e12723, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38978165

RESUMO

BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.


Assuntos
Algoritmos , Macaca nemestrina , Animais , Feminino , Valores de Referência , Testes Hematológicos/veterinária
3.
AIDS Behav ; 26(Suppl 1): 39-50, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34374919

RESUMO

HIV stigma is a barrier to achieving the goals of the US Ending the HIV Epidemic initiative. We analyzed data from the Medical Monitoring Project (MMP) collected during 6/2018-5/2019 from 4050 US adults with diagnosed HIV. We reported national estimates of HIV stigma and assessed their associations with sociodemographic and clinical characteristics. Disclosure concerns and stigma related to negative public attitudes were common. Stigma was higher among younger age groups, women and transgender people, Black and Hispanic/Latino men and women, and Black and Hispanic/Latino men who have sex with men. Stigma was associated with lower antiretroviral therapy use and adherence, missed HIV care visits, and symptoms of depression or anxiety. The estimates presented provide a benchmark from which the nation can monitor its progress. The findings suggest the need for enhanced stigma-reduction efforts among specific groups and the importance of addressing stigma around disclosure and community attitudes.


Assuntos
Infecções por HIV , Pessoas Transgênero , Adulto , Revelação , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Estudos de Amostragem , Estigma Social , Estados Unidos/epidemiologia
4.
Emerg Infect Dis ; 27(8): 2081-2089, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286681

RESUMO

We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso de 80 Anos ou mais , Teste para COVID-19 , Georgia , Humanos , Masculino , Nasofaringe , Saliva , Manejo de Espécimes
5.
J Infect Dis ; 222(3): 391-395, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32128569

RESUMO

We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%-99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%-99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.


Assuntos
Inibidores de Integrase de HIV/administração & dosagem , Piridonas/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Animais , Quimioprevenção/métodos , Modelos Animais de Doenças , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Inibidores de Integrase de HIV/farmacocinética , Macaca mulatta , Masculino , Pênis/virologia , Profilaxia Pré-Exposição , Piridonas/farmacocinética , Vírus da Imunodeficiência Símia/metabolismo
6.
J Infect Dis ; 220(11): 1826-1833, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31362305

RESUMO

BACKGROUND: Tenofovir alafenamide (TAF)-based regimens are being evaluated for pre-exposure prophylaxis (PrEP). We used a macaque model of repeated exposures to simian human immunodeficiency virus (SHIV) to investigate whether TAF alone or the combination of TAF and emtricitabine (FTC) can prevent vaginal infection. METHODS: Pigtail macaques were exposed vaginally to SHIV162p3 once a week for up to 15 weeks. Animals received clinical doses of FTC/TAF (n = 6) or TAF (n = 9) orally 24 hours before and 2 hours after each weekly virus exposure. Infection was compared with 21 untreated controls. RESULTS: Five of the 6 animals in the FTC/TAF and 4 of the 9 animals in the TAF alone group were protected against infection (P = .001 and P = .049, respectively). The calculated efficacy of FTC/TAF and TAF was 91% (95% confidence interval [CI], 34.9%-98.8%) and 57.8% (95% CI, -8.7% to 83.6%), respectively. Infection in FTC/TAF but not TAF-treated macaques was delayed relative to controls (P = .005 and P = .114). Median tenofovir diphosphate (TFV-DP) levels in peripheral blood mononuclear cells (PBMCs) were similar among infected and uninfected macaques receiving TAF PrEP (351 and 143 fmols/106 cells, respectively; P = .921). CONCLUSIONS: Emtricitabine/TAF provided a level of protection against vaginal challenge similar to FTC/TFV disoproxil fumarate combination in the macaque model. Our results support the clinical evaluation of FTC/TAF for PrEP in women.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Transmissão de Doença Infecciosa/prevenção & controle , Emtricitabina/administração & dosagem , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Vagina/virologia , Adenina/administração & dosagem , Alanina , Animais , Quimioprevenção/métodos , Modelos Animais de Doenças , Feminino , HIV/genética , HIV/isolamento & purificação , Macaca , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/isolamento & purificação , Tenofovir/análogos & derivados , Resultado do Tratamento
7.
J Infect Dis ; 218(8): 1284-1290, 2018 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-29788316

RESUMO

Vaginal microbicides containing antiretrovirals (ARVs) have shown to prevent vaginally acquired human immunodeficiency virus (HIV), but these products may not protect women who engage in anal sex. Intravaginal dosing with ARVs has shown to result in drug exposures in rectal tissues, thus raising the possibility of dual compartment protection. To test this concept, we investigated whether intravaginal dosing with emtricitabine (FTC)/tenofovir (TFV) gel, which fully protected macaques against repeated vaginal exposures to simian human immunodeficiency virus (SHIV), protects against rectal SHIV exposures. Pharmacokinetic studies revealed rapid distribution of FTC and TFV to rectal tissues and luminal fluids, albeit at concentrations 1-2 log10 lower than those in the vaginal compartment. Efficacy measurements against repeated rectal SHIV challenges demonstrated a 4.5-fold reduction in risk of infection in macaques that received intravaginal FTC/TFV compared to placebo gel (P = .047; log-rank test). These data support the concept of dual compartment protection by vaginal dosing and warrants developing ARV-based vaginal products with improved bidirectional dosing.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Reto/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Tenofovir/uso terapêutico , Administração Intravaginal , Administração Tópica , Animais , Fármacos Anti-HIV/administração & dosagem , Quimioterapia Combinada , Emtricitabina/administração & dosagem , Feminino , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Tenofovir/administração & dosagem , Cremes, Espumas e Géis Vaginais
8.
Sex Transm Dis ; 44(9): 551-556, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28809773

RESUMO

BACKGROUND: Sustained genital tract inflammation caused by sexually transmitted infections (STIs) is known to increase risk of vaginal human immunodeficiency virus (HIV) infections but, to our knowledge, there are no nonhuman primate studies that have evaluated its link to rectal HIV acquisition. METHODS: Rhesus macaques inoculated with Chlamydia trachomatis (CT) (serovars LGV-L2 and CT-E; n = 7) or saline (n = 7) received up to 20 rectal challenges twice a week of simian/HIV immunodeficiency virus (SHIVSF162p3). SHIV viremia was determined by real-time PCR and Chlamydia infection by APTIMA Combo 2 testing. The rectal cytokine-chemokine levels were evaluated by multiplex bead assays. RESULTS: Rectal Chlamydia infection was maintained throughout the study. We did not observe significant differences (P = 1.0) in frequency of SHIV acquisition between the STI and control arms. It took fewer SHIV challenges to infect the STI animals although the difference was not significant (P = 0.59). There were no significant differences in peak plasma viremia between STI and control arms (P = 0.63). The association of plasma viremia with rectal shedding was significantly different by arm (P = 0.038). CONCLUSIONS: In the first such study in a macaque model, we did not observe an increased risk of SHIV acquisition due to rectal Chlamydia coinfection. This macaque model can be further developed and expanded to better investigate the impact of different rectal STIs on HIV acquisition.


Assuntos
Infecções por Chlamydia/complicações , Coinfecção , Infecções por HIV/complicações , Linfogranuloma Venéreo/complicações , Infecções Sexualmente Transmissíveis/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Animais , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/fisiologia , Modelos Animais de Doenças , Infecções por HIV/virologia , Humanos , Linfogranuloma Venéreo/microbiologia , Macaca mulatta , Reto/microbiologia , Risco , Infecções Sexualmente Transmissíveis/microbiologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia
9.
AIDS ; 38(10): 1560-1569, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38788206

RESUMO

OBJECTIVES: To identify studies promoting the use of artificial intelligence (AI) or automation with HIV preexposure prophylaxis (PrEP) care and explore ways for AI to be used in PrEP interventions. DESIGN: Systematic review. METHODS: We searched in the US Centers for Disease Control and Prevention Research Synthesis database through November 2023; PROSPERO (CRD42023458870). We included studies published in English that reported using AI or automation in PrEP interventions. Two reviewers independently reviewed the full text and extracted data by using standard forms. Risk of bias was assessed using either the revised Cochrane risk-of-bias tool for randomized trials for randomized controlled trials or an adapted Newcastle-Ottawa Quality Assessment Scale for nonrandomized studies. RESULTS: Our search identified 12 intervention studies (i.e., interventions that used AI/automation to improve PrEP care). Currently available intervention studies showed AI/automation interventions were acceptable and feasible in PrEP care while improving PrEP-related outcomes (i.e., knowledge, uptake, adherence, discussion with care providers). These interventions have used AI/automation to reduce workload (e.g., directly observed therapy) and helped non-HIV specialists prescribe PrEP with AI-generated clinical decision-support. Automated tools can also be developed with limited budget and staff experience. CONCLUSIONS: AI and automation have high potential to improve PrEP care. Despite limitations of included studies (e.g., the small sample sizes and lack of rigorous study design), our review suggests that by using aspects of AI and automation appropriately and wisely, these technologies may accelerate PrEP use and reduce HIV infection.


Assuntos
Inteligência Artificial , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Automação , Masculino
10.
Pharmaceutics ; 16(3)2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543278

RESUMO

Pre-exposure prophylaxis (PrEP) with a weekly oral regimen of antiretroviral drugs could be a suitable preventative option for individuals who struggle with daily PrEP or prefer not to use long-acting injectables. We assessed in macaques the efficacy of weekly oral tenofovir alafenamide (TAF) at doses of 13.7 or 27.4 mg/kg. Macaques received weekly oral TAF for six weeks and were exposed twice-weekly to SHIV vaginally or rectally on day 3 and 6 after each dose. Median TFV-DP levels in PBMCs following the 13.7 mg/kg dose were 3110 and 1137 fmols/106 cells on day 3 and 6, respectively. With the 27.4 mg/kg dose, TFV-DP levels were increased (~2-fold) on day 3 and 6 (6095 and 3290 fmols/106 cells, respectively). Both TAF doses (13.7 and 27.4 mg/kg) conferred high efficacy (94.1% and 93.9%, respectively) against vaginal SHIV infection. Efficacy of the 27.4 mg/kg dose against rectal SHIV infection was 80.7%. We estimate that macaque doses of 13.7 and 27.4 mg/kg are equivalent to approximately 230 and 450 mg of TAF in humans, respectively. Our findings demonstrate the effectiveness of a weekly oral PrEP regimen and suggest that a clinically achievable oral TAF dose could be a promising option for non-daily PrEP.

11.
Virus Evol ; 10(1): veae015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510920

RESUMO

We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase (pol) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02_AG (2.5 per cent) and CRF02_AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02_AG/B (24.3 per cent), B/CRF02_AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02_AG-like and CRF02_AG/B, an eighteen-member CRF02_AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02_AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02_AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02_AG, and CRF02_AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02_AG; B and CRF02_AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread.

12.
J Racial Ethn Health Disparities ; 10(1): 56-63, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35060084

RESUMO

To assess the presence of racial disparity during the COVID-19 pandemic, the New Mexico Department of Health (NMDOH) sought to compare the case rate and risk of hospitalization between persons of American Indian and Alaska Native (AI/AN) race and persons of other races in New Mexico from March 1 through September 30, 2020. Using NMDOH COVID-19 surveillance data, age-standardized COVID-19 case and hospitalization risks were compared between adults (≥ 18 years old) of AI/AN and other races. We compared age, sex, and comorbidities between hospitalized adults of AI/AN and other races. Among AI/AN persons, age-standardized COVID-19 case and hospitalization risks were 3.7 (95% CI 3.6-3.8) and 10.5 (95% CI 9.8-11.2) times as high as persons of other races. Hospitalized AI/AN patients had higher proportions of diabetes mellitus (48% vs. 33%, P < 0.0001) and chronic liver disease (8% vs. 5%, P = 0.0004) compared to hospitalized patients of other races. AI/AN populations have disproportionately higher risk of COVID-19 hospitalization compared to other races in New Mexico. By identifying etiologic factors that contribute to inequity, public health partners can implement culturally appropriate health interventions to mitigate disease severity within AI/AN communities.


Assuntos
Nativos do Alasca , COVID-19 , Indígenas Norte-Americanos , Humanos , Adulto , Adulto Jovem , Adolescente , Indígena Americano ou Nativo do Alasca , New Mexico/epidemiologia , Pandemias , Hospitalização
13.
J Acquir Immune Defic Syndr ; 93(2): 134-142, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36812382

RESUMO

BACKGROUND: A collaborative, data-to-care strategy to identify persons with HIV (PWH) newly out-of-care, combined with an active public health intervention, significantly increases the proportion of PWH re-engaged in HIV care. We assessed this strategy's impact on durable viral suppression (DVS). METHODS: A multisite, prospective randomized controlled trial for out-of-care individuals using a data-to-care strategy and comparing public health field services to locate, contact, and facilitate access to care versus the standard of care. DVS was defined as the last viral load, the viral load at least 3 months before, and any viral load between the 2 were all <200 copies/mL during the 18-month postrandomization. Alternative definitions of DVS were also analyzed. RESULTS: Between August 1, 2016-July 31, 2018, 1893 participants were randomized from Connecticut (n = 654), Massachusetts (n = 630), and Philadelphia (n = 609). Rates of achieving DVS were similar in the intervention and standard-of-care arms in all jurisdictions (all sites: 43.4% vs 42.4%, P = 0.67; Connecticut: 46.7% vs 45.0%, P = 0.67; Massachusetts: 40.7 vs 44.4%, P = 0.35; Philadelphia: 42.4% vs 37.3%, P = 0.20). There was no association between DVS and the intervention (RR: 1.01, CI: 0.91-1.12; P = 0.85) adjusting for site, age categories, race/ethnicity, birth sex, CD4 categories, and exposure categories. CONCLUSION: A collaborative, data-to-care strategy, and active public health intervention did not increase the proportion of PWH achieving DVS, suggesting additional support to promote retention in care and antiretroviral adherence may be needed. Initial linkage and engagement services, through data-to-care or other means, are likely necessary but insufficient for achieving DVS for all PWH.


Assuntos
Infecções por HIV , Gravidez , Feminino , Humanos , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Antirretrovirais/uso terapêutico , Massachusetts , Parto , Carga Viral
14.
Addict Behav ; 141: 107637, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36753933

RESUMO

INTRODUCTION: Novel prevention programs are developed to address the increase in e-cigarette use (vaping) among children. However, it remains paramount to test their feasibility in rural settings. This pilot study implemented and evaluated the feasibility and outcomes of two innovative programs, CATCH My Breath and smokeSCREEN, among youth in rural settings in Florida. METHODS: We conducted four focus groups with youth aged 11-17 recruited from 4-H rural clubs in Florida. In a subsequent randomized trial, we recruited 82 youth participants and assigned them to one of three arms: CATCH My Breath, smokeSCREEN, or control. CATCH My Breath and smokeSCREEN participants attended online group intervention sessions while the control group received educational material. Pre- and post-surveys were administered to all participants to assess knowledge, susceptibility, perceived positive outcomes and risk perceptions related to tobacco and e-cigarette use. Other feasibility parameters were also assessed. RESULTS: Focus group discussions provided insights about feasibility and informed the implementation of both interventions in terms of delivery format, scheduling of sessions and incentives. After the intervention, CATCH My Breath participants significantly improved their general tobacco-related knowledge (post-pre = 16.21-12.92 = 3.3, p <.01) and risk perceptions towards other flavored tobacco products (post-pre = 19.29-17.71 = 1.6, p <.05). smokeSCREEN participants significantly improved their general tobacco knowledge (post-pre = 18.77-13.77 = 5.0, p <.01), knowledge about e-cigarettes (post-pre = 9.08-6.31 = 2.8, p <.01) and risk perception towards e-cigarettes (post-pre = 24.69-21.92 = 2.8, p <.05). CONCLUSIONS: This study demonstrated feasibility of delivering the interventions via participant engagement, participants' willingness to be randomized, assessment of outcome measures, and exploration of different recruitment methods. Despite the potential positive influence of CATCH My Breath and smokeSCREEN on youth participants, further evaluation with larger samples is needed.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabagismo , Vaping , Criança , Humanos , Adolescente , Vaping/prevenção & controle , Florida , Projetos Piloto
15.
AIDS ; 36(2): 169-176, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482355

RESUMO

OBJECTIVE: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STIs) that are known to increase HIV susceptibility in women. DESIGN: Two macaque models of increasing vaginal STI severity were used for efficacy assessment. METHODS: The first study (n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis and Trichomonas vaginalis. Six animals were CAB-LA treated and five were controls. The second study (n = 9) included a triple STI model with repeated exposures to C. trachomatis, T. vaginalis and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared with untreated controls over time. RESULTS: All six CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges, while the untreated animals became SHIV-infected after a median of two challenges (log-rank P < 0.001) or one challenge (log-rank P = 0.002), respectively. Both models recapitulated human STI disease, with vaginal discharge, ulcers, and seroconversion. CONCLUSION: In these high and sustained susceptibility models spanning more than 3 months, CAB-LA maintained complete efficacy, demonstrating robustness of the CAB-LA dose used in clinical trials, and suggesting its insensitivity to multiple STIs and DMPA.


Assuntos
Infecções por HIV , Infecções Sexualmente Transmissíveis , Síndrome de Imunodeficiência Adquirida dos Símios , Animais , Dicetopiperazinas , Feminino , Infecções por HIV/prevenção & controle , Humanos , Macaca , Acetato de Medroxiprogesterona , Piridonas , Infecções Sexualmente Transmissíveis/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle
16.
EBioMedicine ; 86: 104361, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36423375

RESUMO

BACKGROUND: Vaginal products for HIV prevention that can be used on-demand before or after sex may be a preferable option for women with low frequency or unplanned sexual activity or who prefer not to use daily or long-acting pre-exposure prophylaxis (PrEP). We performed dose ranging pharmacokinetics (PK) and efficacy studies of a vaginally applied insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) in macaques under PrEP or post-exposure prophylaxis (PEP) modalities. METHODS: PK studies were performed in 3 groups of pigtailed macaques receiving inserts with different fixed-dose combinations of TAF and EVG (10/8, 20/16 and 40/24 mg). PrEP and PEP efficacy of a selected insert was investigated in a repeat exposure vaginal SHIV transmission model. Inserts were administered 4 h before (n = 6) or after (n = 6) repeated weekly SHIV exposures. Infection outcome was compared with macaques receiving placebo inserts (n = 12). FINDINGS: Dose ranging studies showed rapid and sustained high drug concentrations in vaginal fluids and tissues across insert formulations with minimal dose proportionality. TAF/EVG (20/16 mg) inserts were selected for efficacy evaluation. Five of the 6 animals receiving these inserts 4 h before and 6/6 animals receiving inserts 4 h after SHIV exposure were protected after 13 challenges (p = 0.0088 and 0.0077 compared to placebo, respectively). The calculated PrEP and PEP efficacy was 91.0% (95% CI = 32.2%-98.8%) and 100% (95% CI = undefined), respectively. INTERPRETATION: Inserts containing TAF/EVG provided high protection against vaginal SHIV infection when administered within a 4 h window before or after SHIV exposure. Our results support the clinical development of TAF/EVG inserts for on-demand PrEP and PEP in women. FUNDING: Funded by CDC intramural funds, an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002), and by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID) under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Animais , Feminino , Adenina , Fármacos Anti-HIV/uso terapêutico , Fumaratos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Macaca , Tenofovir/uso terapêutico
17.
PLoS One ; 17(3): e0264085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35263342

RESUMO

Self-collected specimens can expand access to SARS-CoV-2 testing. At a large inner-city hospital 1,082 participants self-collected saliva and anterior nasal swab (ANS) samples before healthcare workers collected nasopharyngeal swab (NPS) samples on the same day. To characterize patient preferences for self-collection, this investigation explored ability, comfort, and ease of ANS and saliva self-collection for SARS-CoV-2 testing along with associated patient characteristics, including medical history and symptoms of COVID-19. With nearly all participants successfully submitting a specimen, favorable ratings from most participants (at least >79% in ease and comfort), and equivocal preference between saliva and ANS, self-collection is a viable SARS-CoV-2 testing option.


Assuntos
COVID-19/diagnóstico , Manejo de Espécimes/métodos , Adolescente , Adulto , COVID-19/virologia , Teste para COVID-19 , Feminino , Georgia , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , RNA Viral/análise , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Adulto Jovem
18.
Front Public Health ; 10: 809356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425748

RESUMO

We aimed to describe frequency of COVID-19 exposure risk factors among patients presenting for medical care at an urban, public hospital serving mostly uninsured/Medicare/Medicaid clients and risk factors associated with SARS-CoV-2 infection. Consenting, adult patients seeking care at a public hospital from August to November 2020 were enrolled in this cross-sectional investigation. Saliva, anterior nasal and nasopharyngeal swabs were collected and tested for SARS-CoV-2 using RT-PCR. Participant demographics, close contact, and activities ≤14 days prior to enrollment were collected through interview. Logistic regression was used to identify risk factors associated with testing positive for SARS-CoV-2. Among 1,078 participants, 51.8% were male, 57.0% were aged ≥50 years, 81.3% were non-Hispanic Black, and 7.6% had positive SARS-CoV-2 tests. Only 2.7% reported COVID-19 close contact ≤14 days before enrollment; this group had 6.79 adjusted odds of testing positive (95%CI = 2.78-16.62) than those without a reported exposure. Among participants who did not report COVID-19 close contact, working in proximity to ≥10 people (adjusted OR = 2.17; 95%CI = 1.03-4.55), choir practice (adjusted OR = 11.85; 95%CI = 1.44-97.91), traveling on a plane (adjusted OR = 5.78; 95%CI = 1.70-19.68), and not participating in an essential indoor activity (i.e., grocery shopping, public transit use, or visiting a healthcare facility; adjusted OR = 2.15; 95%CI = 1.07-4.30) were associated with increased odds of testing positive. Among this population of mostly Black, non-Hispanic participants seeking care at a public hospital, we found several activities associated with testing positive for SARS-CoV-2 infection in addition to close contact with a case. Understanding high-risk activities for SARS-CoV-2 infection among different communities is important for issuing awareness and prevention strategies.


Assuntos
COVID-19 , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos Transversais , Feminino , Georgia/epidemiologia , Hospitais Públicos , Humanos , Masculino , Medicare , Fatores de Risco , SARS-CoV-2 , Estados Unidos
19.
J Acquir Immune Defic Syndr ; 86(2): e48-e53, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33136820

RESUMO

BACKGROUND: Black and Hispanic men have the highest rates of HIV diagnoses. To decrease the number of U.S. men who are unaware of their HIV status, they should be tested at least once. Our objective was to estimate the increases needed in HIV testing rates at ambulatory health care visits to achieve universal coverage. METHODS: We analyzed nationally representative medical record abstraction data to estimate the number of visits per person to physician offices, emergency departments, and outpatient clinics among men aged 18-39 years during 2009-2016, and the percentage of visits with an HIV test. We calculated the increase in the percentage of visits with an HIV test needed to achieve universal testing coverage of men by age 39 years. RESULTS: Men had a mean of 75.3 million ambulatory visits per year and 1.67 visits per person. An HIV test was performed at 0.9% of the ambulatory visits made by white men, 2.5% by black men, and 2.4% by Hispanic men. A 3-fold increase in the percentage of visits with an HIV test would result in coverage of 46.2% of white, 100% of black, and 100% of Hispanic men; an 11-fold increase would be needed to result in coverage of 100% of white men. CONCLUSIONS: HIV testing rates of men at ambulatory health care visits were too low to provide HIV testing coverage of all men by aged 39 years. A 3-fold increase in the percentage of visits with an HIV test would result in universal testing coverage of black and Hispanic men by age 39 years.


Assuntos
Instituições de Assistência Ambulatorial , Assistência Ambulatorial , Benchmarking , Atenção à Saúde , Infecções por HIV/diagnóstico , Cobertura Universal do Seguro de Saúde , Adolescente , Adulto , Negro ou Afro-Americano , Serviço Hospitalar de Emergência , Hispânico ou Latino , Humanos , Visita a Consultório Médico , Consultórios Médicos , Estados Unidos , População Branca , Adulto Jovem
20.
Antiviral Res ; 186: 105001, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33385420

RESUMO

Prevention of HIV infection and unintended pregnancies are public health priorities. In sub-Saharan Africa, where HIV prevalence is highest, depot medroxyprogesterone acetate (DMPA) is widely used as contraception. Therefore, understanding potential interactions between DMPA and antiretrovirals is critical. Here, we use a macaque model to investigate the effect of DMPA on the pharmacology of the antiretroviral tenofovir alafenamide (TAF). Female rhesus macaques received 30 mg of DMPA (n = 9) or were untreated (n = 9). Macaques received a human equivalent dose of TAF (1.5 mg/kg) orally by gavage. Tenofovir (TFV) and TFV-diphosphate (TFV-DP) were measured in blood, secretions, and tissues over 72 h. The median area under the curve (AUC0-72h) values for TFV-DP in peripheral blood mononuclear cells were similar in DMPA-treated (6991 fmol*h/106 cells) and untreated controls (5256 fmol*h/106 cells) (P = 0.174). Rectal tissue TFV-DP concentrations from DMPA+ animals [median: 20.23 fmol/mg of tissue (range: 4.94-107.95)] were higher than the DMPA- group [median: below the limit of quantification (BLOQ-11.92)], (P = 0.019). TFV-DP was not detectable in vaginal tissue from either group. A high-dose DMPA treatment in macaques was associated with increased rectal TFV-DP levels, indicating a potential tissue-specific drug-drug interaction. The lack of detectable TFV-DP in the vaginal tissue warrants further investigation of PrEP efficacy with single-agent TAF products. DMPA did not affect systemic TAF metabolism, with similar PBMC TFV-DP in both groups, suggesting that DMPA use should not alter the antiviral activity of TAF.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Anticoncepcionais Femininos/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Tenofovir/administração & dosagem , Animais , Fármacos Anti-HIV/análise , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacologia , Interações Medicamentosas , Feminino , Infecções por HIV/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Macaca mulatta , Acetato de Medroxiprogesterona/análise , Acetato de Medroxiprogesterona/sangue , Acetato de Medroxiprogesterona/farmacologia , Modelos Animais , Tenofovir/análise , Tenofovir/sangue , Tenofovir/farmacologia
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