RESUMO
T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2-specific T cells can be expanded from convalescent donors and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a good manufacturing practice-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited interferon-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T-cell responses, which may be critical for the development of effective vaccine and T-cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation.
Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Técnicas de Cultura de Células/métodos , Imunoterapia Adotiva/métodos , SARS-CoV-2/imunologia , Adulto , Idoso , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Epitopos Imunodominantes/imunologia , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Proteínas Virais/imunologia , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
OBJECTIVE: To evaluate the uptake of perinatal HIV preventive interventions by the risk of perinatal HIV transmission in mother-infant pairs in a high-HIV prevalence area in the US. STUDY DESIGN: This was a retrospective cohort study of mother-infant pairs with perinatal HIV exposure during 2013-2017 managed at a subspecialty pediatric HIV program in Washington, DC. We collected demographic data, maternal HIV history, delivery mode, maternal and infant antiretroviral drug (ARV) use, and infant HIV test results. We compared the uptake of recommended preventive interventions in low-risk (ie, mothers on antiretroviral therapy [ART] with viral suppression) and high-risk (mothers without ART or viral suppression) mother-infant pairs using the Pearson chi-square, Fisher exact, and Wilcoxon rank-sum tests and logistic regression. RESULTS: We analyzed 551 HIV-exposed infants (HEIs) and 542 mothers living with HIV. The majority of mothers received ARVs (95.5%), had HIV RNA ≤1000 copies/mL before delivery (81.9%), and received intrapartum zidovudine (ZDV; 65.5%). The majority of all HEIs were low risk (82.6%) and received postpartum ARVs (98.9%). Among the low-risk infants, 53.2% were delivered via cesarean delivery (CD), and 62.9% and 96.5% were administered intrapartum and postpartum ZDV, respectively. Among high-risk infants, 84.4% were delivered via CD, 78.1% received intrapartum ZDV, and 62.5% received combination ART. Nine high-risk infants acquired HIV perinatally. CONCLUSION: In an area of high HIV prevalence in the US, a large proportion of low-risk HEIs received intrapartum ZDV and were delivered via CD. We also observed missed opportunities for the prevention of perinatal HIV transmission.
Assuntos
DNA Viral/análise , Infecções por HIV/prevenção & controle , HIV/genética , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Período Pós-Parto , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Feminino , Infecções por HIV/epidemiologia , Humanos , Recém-Nascido , Masculino , Gravidez , Prevalência , Prognóstico , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
AIM AND OBJECTIVES: To describe the lived experience of young adults with perinatally acquired HIV (PaHIV). BACKGROUND: With the advancement of the highly active antiretroviral treatment, PaHIV infection has transformed into a chronic lifelong illness that is faced by young adults who grew up with HIV. The known challenges that are associated with HIV are poverty, stigma and social and emotional isolation. DESIGN: This was a qualitative single-interview study of a convenience sample of PaHIV-infected young adults receiving care at a large metropolitan pediatric hospital. METHODS: The participants had individual face-to-face interviews which were audio-taped and transcribed verbatim. Themes were developed to describe their living space, and Max Van Manen's lifeworld guide was used to describe their lived experience. FINDINGS: Seventeen participants (eight males/nine females) were enrolled. Four major themes emerged: (i) limited social capital, especially when orphaned participants reflected on a life void of parental guidance; (ii) incomplete education and unemployment, participants described an idle existence; (iii) a harsh life, described as participants facing difficulties meeting their life's milestones; (iv) unanticipated adult issues, where participants described their limited ability to care for themselves and their children. Van Manen lifeworld themes also described the space they occupied, their memories growing up with PaHIV, their health care and relationships. CONCLUSION: Our study provides a valuable insight into the social and emotional difficulties faced by youth with PaHIV. The findings underscore the importance of extensive support and coordination of services between adult and pediatric providers to optimize long-term outcomes among young adults with PaHIV. RELEVANCE TO CLINICAL PRACTICE: The young adults with PaHIV require close attention and support from the healthcare providers, who can offer them a safe space to discuss lived experiences and support their ability to achieve full lives.
Assuntos
Infecções por HIV/congênito , Infecções por HIV/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pobreza , Pesquisa Qualitativa , Estigma Social , Fatores Socioeconômicos , Adulto JovemRESUMO
Background: In global health, international nongovernmental organizations (NGOs) frequently hire, train, and partner with host-country clinicians who manage public outreach and patient care. Purpose and Research Design: We conducted a general interpretivist study of Basotho clinicians hired by NGOs and academic affiliates in Lesotho to identify cultural barriers and facilitators to community and patient education. Data Collection and Analysis: We conducted 13 interviews involving 16 participants (one physician, one nutritionist, 14 nurses). Using an inductive and iterative approach, we analyzed interview transcripts through the lens of social cognitive theory and identified 15 themes. Results: Major findings highlighted: 1) patient and community learners may view Basotho clinicians as authority figures; 2) family and community power dynamics affect healthcare access for vulnerable patient groups; and 3) village leaders may refuse community education when excluded from problem-solving and early planning. Conclusions: Although local clinicians and community members may identify with the same cultural group, clinicians can encounter cultural barriers to patient and community education.
Assuntos
Resíduos de Alimentos , Saúde Global , Humanos , Lesoto , Pesquisa Qualitativa , Processos GrupaisRESUMO
We report a case of sustained viral suppression with dolutegravir monotherapy in a treatment-experienced adult with perinatally acquired HIV. The patient had recurrent pancreatitis with multiple antiretroviral drugs, leading to discontinuation of antiretroviral therapy for several years. She was ultimately initiated on dolutegravir monotherapy two times per day via a gastrostomy tube. She did not develop any integrase strand transfer inhibitor mutations during the first 2 years on dolutegravir monotherapy. The patient has successfully maintained prolonged viral suppression for over 3 years with intermittent blips secondary only to intermittent medical issues. This case is unique in describing a highly treatment-experienced young adult with perinatal HIV infection who has been virally suppressed on dolutegravir monotherapy for a prolonged follow-up of 156 weeks.
Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis , Humanos , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Resposta Viral Sustentada , Carga ViralRESUMO
Among 185 Black, cis-gender, predominantly heterosexual adolescents and young adults (AYA) and 35 guardians surveyed in Washington, DC, the majority of AYA (96.8%) and guardians (94.3%) were unaware of pre-exposure prophylaxis (PrEP); 62.2% of AYA were uncertain if PrEP was safe or effective against HIV. Of 41.6% of AYA willing to use PrEP, 24.9% reported concern about PrEP-related social stigma.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Heterossexualidade/estatística & dados numéricos , Profilaxia Pré-Exposição , Adolescente , Estudos Transversais , District of Columbia , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e Questionários , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
An adolescent female patient presenting with subacute onset of dysphagia and hoarseness underwent a direct laryngoscopy, which revealed epiglottitis. After 2 hospitalizations and multiple consultations and biopsies, all infectious testing results for viral, bacterial, fungal, and acid-fast bacilli etiologies were negative. The patient's use of electronic cigarettes was the only exposure elicited with a likely role in her presentation. This case, combined with the growing body of evidence revealing the toxic effects of vaping and the increasing use of electronic cigarettes among adolescent patients, highlights the many unknowns and risks regarding the biological effects of this practice.