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BACKGROUND: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. METHODS: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. RESULTS: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. CONCLUSION: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.
Doctor and clinic staff perspectives on a program to immediately start HIV treatment among patients newly diagnosed with HIVTreating human immunodeficiency virus (HIV) is easier than ever. Starting newly diagnosed persons on HIV medication as soon as possible is a now recommended goal. However, starting patients right away can be challenging. This study interviewed doctors and clinic staff to better understand their perspectives prior to implementing a program that would provide newly diagnosed patients with HIV treatment immediately. Results showed that some doctors are worried patients will not return after receiving their medications. Providers want support for linking patients to the clinic and ensuring they will be able to receive their next dose of medication when they come in. Other providers saw the benefits of reducing HIV stigma if the program can more quickly start patients on treatment. Some providers explained that when you go to the doctor and are sick you receive medications immediately, yet for newly diagnosed patients living with HIV, patients can be told to come back a month later to start treatment. Some providers believe shifting this messaging may also help patients take their medications better. Most providers saw the need for clinics to have more same-day appointment availability to meet the needs of the new program. Overall, providers were excited about the opportunity to improve the HIV care by offering HIV medications to newly diagnosed patients immediately.
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Actitud del Personal de Salud , Infecciones por VIH , Investigación Cualitativa , Humanos , Infecciones por VIH/tratamiento farmacológico , North Carolina , Masculino , Femenino , Fármacos Anti-VIH/uso terapéutico , Adulto , Tiempo de Tratamiento/estadística & datos numéricos , Personal de Salud/psicología , Persona de Mediana EdadRESUMEN
The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.
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Microbioma Gastrointestinal , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Boca/microbiología , Índice de Masa Corporal , Heces/microbiología , Antirretrovirales/uso terapéutico , Saliva/microbiologíaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) affects almost 10% of the global populace including people living with HIV (PLWH). PLWH acquire CKD from both traditional and HIV-specific CKD risk factors. This study aimed to determine the prevalence of CKD and associated factors among antiretroviral therapy (ART) naïve PLWH in Lagos, Nigeria. METHODS: This is a secondary data analysis among adult (≥ 18 years) ART-naïve PLWH enrolled at a large ART clinic in Lagos over 6 years. CKD was defined as estimated glomerular filtration rates (eGFR) below 60ml/min/1.73m2 over 3 months. Three estimators [Body surface area corrected Cockcroft Gault (BSA-CG), Modification of Diet in Renal Disease (MDRD), Chronic kidney disease Epidemiology Collaboration (CKD-EPI)] were used to determine the burden of CKD with no race correction factor. Age- and sex-standardised prevalence rates were determined. Cohen Kappa and Spearman correlations were used to compare the estimators. Logistic regressions were applied to identify variables associated with prevalent CKD. RESULTS: Among 2 772 PLWH, the mean age was 38 years with males older than females (p < 0.001). The majority of participants were females (62.1%), married (54.8%), employed (85.7%), had underweight or normal body mass index (BMI) (62.2%), and were diagnosed with World Health Organization (WHO) clinical stages 1 and 2 (55.5%). The age- and sex-standardised prevalence of CKD ranged from 10.0 - 17.6% with the highest Spearman's correlation (0.928) observed with MDRD and CKD-EPI equations. Increasing age [AOR (95% CI), equation] was significantly associated with CKD across all equations [1.09 (1.06 - 1.13), BSA-CG; 1.07 (1.05 - 1.10), MDRD; 1.09 (1.06 -1.12), CKD-EPI]. Other variables associated with CKD [AOR (95% CI), equation] were anaemia [2.50 (1.34 - 4.68), BSA-CG; 1.73 (1.04 - 2.86), MDRD], BMI <25 kg/m2 [3.35 (1.55 - 7.26), BSA-CG; 2.02 (1.18 - 3.46), CKD-EPI], and CD4 counts ≤ 200 cells/µL [2.02 (1.06 - 3.87), BSA-CG]. CONCLUSION: There was a high prevalence of CKD among ART-naïve PLWH at enrollment, which highlights the need to evaluate this population for CKD. Aside increasing age and low CD4 counts, none of the traditional or HIV-specific risk factors were related to CKD diagnosis.
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Infecciones por VIH , Insuficiencia Renal Crónica , Humanos , Nigeria/epidemiología , Masculino , Femenino , Adulto , Insuficiencia Renal Crónica/epidemiología , Prevalencia , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Persona de Mediana Edad , Tasa de Filtración Glomerular , Factores de Riesgo , Adulto Joven , Estudios TransversalesRESUMEN
BACKGROUND: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage. The effects of HIV and smoking on pulmonary mucosal CD8 T-cell dynamics has been a neglected area of research, which we address herein. METHODS: Bronchoalveolar lavage (BAL) fluid were obtained from ART-treated PLWH (median duration of supressed viral load: 9 years; smokers: n = 14; non-smokers: n = 21) and HIV-uninfected controls (smokers: n = 11; non-smokers: n = 20) without any respiratory symptoms or active infection. Lymphocytes were isolated and CD8 T-cell subsets and homing markers were characterized by multiparametric flow cytometry. RESULTS: Both smoking and HIV infection were independently associated with a significant increase in frequencies of total pulmonary mucosal CD8 T-cell. BAL CD8 T-cells were primarily CD69 + expressing CD103 and/or CD49a, at least one of the two granzymes (GzmA/GzmB), and little Perforin. Higher expression levels of CD103, CD69, and GzmB were observed in smokers versus non-smokers. The ex vivo phenotype of GzmA + and GzmB + cells revealed increased expression of CD103 and CXCR6 in smokers, while PLWH displayed elevated levels of CX3CR1 compared to controls. CONCLUSION: Smoking and HIV could promote cytotoxic CD8 T-cell retention in small airways through different mechanisms. Smoking likely increases recruitment and retention of GzmB + CD8 Trm via CXCR6 and CD103. Heightened CX3CR1 expression could be associated with CD8 non-Trm recruitment from the periphery in PLWH.
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Infecciones por VIH , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Femenino , Persona de Mediana Edad , Adulto , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/metabolismo , Fumar/efectos adversos , Líquido del Lavado Bronquioalveolar/inmunología , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Pulmón/inmunología , Pulmón/efectos de los fármacos , Pulmón/metabolismoRESUMEN
Cancer patients living with HIV (CPLWH) may experience increased mortality risk. Furthermore, they have been historically excluded from clinical trials due to safety concerns. Our patient with squamous cell carcinoma of the lower lip received radiotherapy and platinum-based chemotherapy but declined by multiple centers due to his accidental HIV status. Genomic profiling revealed CDKN2A/B, PBRM1, TP53, and TERT alterations corresponding to UV signature, and high tumor mutational burden with positive PD-L1 staining. Accordingly, we report a durable radiologic and molecular complete response upon nivolumab plus IVC and antiretroviral therapy (ART). We demonstrated the safety and efficacy of ICIs, and feasibility of managing adverse events caused by antitumor, antiviral, and integrative therapies.
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Infecciones por VIH , Nivolumab , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Nivolumab/uso terapéutico , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
BACKGROUND: Both sleep-related breathing disorders (SRBDs) and HIV infection can interfere with normal sleep architecture, and also cause physical and psychological distress. We aimed to understand the differences in the obstructive patterns, sleep architecture, physical and psychological distress when compared between people living with HIV (PLWH) and matched the severity of SRBDs controls. METHODS: A comparative study using matched case-control design was conducted. Men with HIV infection (case group) were enrolled from 2016 to 2019. A control group with HIV seronegative men were matched for SRBDs severity, and were selected from sleep medicine center database for comparison. RESULTS: The mean age of the 108 men (including 54 cases and 54 matched controls) was 33.75 years. Central-apnea index (CI) was higher in the case group rather than matched controls (mean CI, 0.34 vs. 0.17, p = 0.049). PLWH had a lower mean percentage of stage 3 sleep (10.26% vs. 13.94%, p = 0.034) and a higher percentage of rapid eye movement sleep (20.59% vs. 17.85%, p = 0.011) compared to matched controls. Nocturnal enuresis and sleepiness causing traffic accidents were more frequent complaint in PLWH compared to controls. CONCLUSIONS: Early detected SRBDs and subtypes in PLWH to begin treatment for the underlying cause could reduce the risk of sleepiness-related traffic accidents.
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Infecciones por VIH , Polisomnografía , Síndromes de la Apnea del Sueño , Humanos , Masculino , Estudios de Casos y Controles , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/fisiopatología , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/diagnóstico , Persona de Mediana EdadRESUMEN
Introduction: People living with HIV (PLWH) now benefit from combined antiviral treatments that durably control viral replication. These antiretroviral treatments decrease mortality and improve quality of life in PLWH, but do not completely control the excessive non-specific activation of the immune system in PLWH. This chronic immune activation is a key element of HIV immunopathology that contributes to the pathophysiology of inflammatory comorbid conditions, such as cardiovascular disorders, cancer and autoimmune diseases. Circulating non-exosomal extracellular vesicles, also known as microparticles (MPs) are detected in these diseases and have been linked to immune activation. The objective of this study was to characterize the MPs present in PLWH and to assess their association with chronic immune activation. Methods: We performed flow cytometry for the complete phenotypic characterization of MPs from fresh plasma from PLWH and from people without HIV as the control group. The absolute number, size and cellular origin of MPs were evaluated. The immunoregulatory profile was determined by cell origin, for MPs derived from platelets (PMPs), monocytes (MMPs) and T lymphocytes (LMPs). Results: PLWH had significantly more circulating MPs than controls, for MPs of all sizes originating from T lymphocytes, red blood cells, neutrophils, dendritic cells, B lymphocytes and endothelial cells. PMPs and MMPs were not more numerous in PLWH, but the immunoregulatory phenotypes of these MPs differed between PLWH and controls. These differences in immunoregulatory molecule expression profile were also observed for LMPs. PDL1, ICOSL, CCR5, TGFß1, MHC classes I and II, TRAIL, CXCR4, OX40, DC-SIGN, CTLA4 and PDL2 were more strongly expressed on the surface of MPs from PLWH than on those from controls. Conclusion: MPs are an important element in intercellular communication, making it possible to transfer phenotypes and functions to immune cells. The significantly higher numbers of MPs expressing diverse immunomodulatory molecules in PLWH may make a major contribution to the maintenance and/or the development of immune-cell activation in these individuals.
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Células Endoteliales , Infecciones por VIH , Humanos , Calidad de Vida , Linfocitos T , PlaquetasRESUMEN
BACKGROUND: The COVID-19 pandemic profoundly affected healthcare services, including HIV patient care. This study assessed the impact of the pandemic on diverse aspects of care for individuals living with HIV (PLWH). METHODS: Patient data from 2019 to 2021 were collected using the Cascades template, provided by the New York State Department of Health, focusing on viral testing and suppression outcomes. Age, ethnicity, sex, and race were considered variables and analyzed via chi-square analysis, logistic regression model, and F test. RESULTS: The pandemic significantly reduced viral testing in 2020 due to restrictions and closures, but telemedicine and tele-pharmacy helped maintain care. Age was a crucial factor, predicting higher viral testing and suppression odds for older individuals, but no significant differences were observed between patient gender, race, or ethnicity in obtaining viral testing or achieving suppression. CONCLUSIONS: While limitations existed, this study provides insights into sustaining care during crises, highlighting the importance of innovative healthcare delivery methods and age-sensitive approaches for PLWH.
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Síndrome de Inmunodeficiencia Adquirida , Linfoma de Células B Grandes Difuso , Infecciones por Mycobacterium no Tuberculosas , Infección por Mycobacterium avium-intracellulare , Humanos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Micobacterias no Tuberculosas , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnósticoRESUMEN
Long-acting injectable antiretroviral therapy (LAI-ART) can offer people living with HIV (PLWH) a promising alternative to daily oral therapy. This article highlights the issues, challenges and conditions related to introducing LAI-ART into the social lives of PLWH and HIV-care practices in Senegal. Semi-structured interviews were conducted with 42 PLWH in two hospital care units in Dakar and with 13 healthcare providers and 6 peer educators. Interviews were transcribed, thematically coded and analysed using a cross-sectional approach. We found three key issues. First, simplifying living with HIV: PLWH respondents perceive LAI-ART as an opportunity to ease the burden associated with taking tablets. This enthusiasm may however be qualified by an ambivalent relationship with injections and is subject to certain conditions. Second, certain constraints linked to the medicalisation of care are to be anticipated, including the obligation to go to the hospital every two months for injections. These findings foreshadow the new management work for medical follow-up expected to fall on PLWH and caregivers. Third, the challenges of introducing LAI-ART in Senegal are to ensure adequate organisation of care and supply and sustainability of the program. These results clarify how to implement programs to introduce LAI-ART into real life in the West African context.
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Infecciones por VIH , Humanos , Senegal , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Investigación Cualitativa , Personal de SaludRESUMEN
BACKGROUND: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders. METHODS: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan. RESULTS: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction. CONCLUSIONS: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH , Inhibidores de Integrasa VIH , Humanos , Animales , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , Caenorhabditis elegans , Longevidad , Infecciones por VIH/tratamiento farmacológico , Especies Reactivas de OxígenoRESUMEN
Introduction COVID-19 most commonly causes pulmonary/lung infection, and these pulmonary diseases can complicate HIV infection. Underlying pulmonary diseases in people living with HIV (PLWH) could affect health outcomes if infected with COVID-19. Therefore, this study was designed to determine the impact of pulmonary diseases on the health outcomes of PLWH that were infected with COVID-19. Materials and methods We conducted a retrospective study to assess the impact of superimposed COVID-19 infection on pre-existing lung pathologies in patients living with human immunodeficiency virus (HIV) infection using data from the Minnesota Fairview network from January 1, 2020 to December 31, 2022. Ordinal logistic regressions were used to determine the effect of lung comorbidities on COVID-19 severity, COVID-19-specific mortality, and all-cause mortality, adjusting for patient age and gender. Results Two hundred sixteen PLWH tested positive for COVID-19. 24.54% of these patients had one or more pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other lung diseases (interstitial lung diseases and pulmonary hypertension). The severity of COVID-19 outcomes was evaluated by the ranking of patients' medical records of testing positive, admitted to the hospital, being admitted to the ICU, and death. COVID-19-specific and all-cause mortality were evaluated separately. PLWH with underlying asthma or COPD was not associated with increased all-cause or COVID-19-specific mortality. Interstitial lung disease or pulmonary hypertension was significantly associated with poor health outcomes for COVID-19-specific mortality and all-cause mortality (Fisher's Exact p-value <0.001), with ICU admissions accounting for the most impact. Using the multivariate models, interstitial lung disease and pulmonary hypertension was significantly associated with an increased risk of more severe COVID-19 outcomes and COVID-19-specific mortality (OR=6.6153, CI=2.5944, 17.0795, p-value < 0.001). Interstitial lung disease and pulmonary hypertension were also significantly associated with an increased risk of more severe COVID-19 outcomes and all-cause mortality (OR=ââ5.0885, CI=2.0590, 12.5542, p-value < 0.001). Conclusions To mitigate the poor outcomes associated with interstitial lung diseases and pulmonary hypertension in PLWH due to COVID-19, healthcare providers must educate their patients about safety measures against the COVID-19 vaccine. They can also encourage the COVID-19 vaccine uptake among their eligible patients.
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The kinetics of Fc-mediated functions following SARS-CoV-2 infection or vaccination in people living with HIV (PLWH) are not known. We compared SARS-CoV-2 spike-specific Fc functions, binding, and neutralization in PLWH and people without HIV (PWOH) during acute infection (without prior vaccination) with either the D614G or Beta variants of SARS-CoV-2, or vaccination with ChAdOx1 nCoV-19. Antiretroviral treatment (ART)-naïve PLWH had significantly lower levels of IgG binding, neutralization, and antibody-dependent cellular phagocytosis (ADCP) compared with PLWH on ART. The magnitude of antibody-dependent cellular cytotoxicity (ADCC), complement deposition (ADCD), and cellular trogocytosis (ADCT) was differentially triggered by D614G and Beta. The kinetics of spike IgG-binding antibodies, ADCC, and ADCD were similar, irrespective of the infecting variant between PWOH and PLWH overall. However, compared with PWOH, PLWH infected with D614G had delayed neutralization and ADCP. Furthermore, Beta infection resulted in delayed ADCT, regardless of HIV status. Despite these delays, we observed improved coordination between binding and neutralizing responses and Fc functions in PLWH. In contrast to D614G infection, binding responses in PLWH following ChAdOx-1 nCoV-19 vaccination were delayed, while neutralization and ADCP had similar timing of onset, but lower magnitude, and ADCC was significantly higher than in PWOH. Overall, despite delayed and differential kinetics, PLWH on ART develop comparable responses to PWOH, supporting the prioritization of ART rollout and SARS-CoV-2 vaccination in PLWH.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Citotoxicidad Celular Dependiente de Anticuerpos , COVID-19 , Infecciones por VIH , Fragmentos Fc de Inmunoglobulinas , Glicoproteína de la Espiga del Coronavirus , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Fragmentos Fc de Inmunoglobulinas/sangre , Fragmentos Fc de Inmunoglobulinas/inmunología , ChAdOx1 nCoV-19/inmunología , ChAdOx1 nCoV-19/uso terapéutico , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Vacunación , Glicoproteína de la Espiga del Coronavirus/inmunología , Células HEK293 , Humanos , Inmunidad Humoral , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
Human cytomegalovirus (CMV) infection drives the expansion and differentiation of natural killer (NK) cells with adaptive-like features. We investigated whether age and time on antiretroviral therapy (ART) influenced adaptive NK cell frequency and functionality. Flow cytometry was used to evaluate the frequency of adaptive and conventional NK cells in 229 CMV+ individuals of whom 170 were people living with HIV (PLWH). The frequency of these NK cell populations producing CD107a, CCL4, IFN-γ or TNF-α was determined following a 6-h antibody dependent (AD) stimulation. Though ART duration and age were correlated, longer time on ART was associated with a reduced frequency of adaptive NK cells. In general, the frequency and functionality of NK cells following AD stimulation did not differ significantly between treated CMV+PLWH and CMV+HIV- persons, suggesting that HIV infection, per se, did not compromise AD NK cell function. AD activation of adaptive NK cells from CMV+PLWH induced lower frequencies of IFN-γ or TNF-α secreting cells in older persons, when compared with younger persons.
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Coinfección , Infecciones por Citomegalovirus , Infecciones por VIH , Anciano , Anciano de 80 o más Años , Humanos , Infecciones por Citomegalovirus/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Células Asesinas Naturales , Factor de Necrosis Tumoral alfa , Antígenos CD57/inmunologíaRESUMEN
In people living with HIV-1 (PLWH), antiretroviral therapy (ART) eventually becomes necessary to suppress the emergence of human immunodeficiency virus type 1 (HIV-1) replication from latent reservoirs because HIV-1-specific immune responses in PLWH are suboptimal. Immunotherapies that enhance anti-HIV-1 immune responses for better control of virus reemergence from latent reservoirs are postulated to offer ART-free control of HIV-1. Toward the goal of developing an HIV-1-specific immunotherapy based on non-thermal plasma (NTP), the early immunological responses to NTP-exposed latently infected T lymphocytes were examined. Application of NTP to the J-Lat T-lymphocyte cell line (clones 10.6 and 15.4) stimulated monocyte recruitment and macrophage maturation, which are key steps in initiation of an immune response. In contrast, CD8+ T lymphocytes in a mixed lymphocyte reaction assay were not stimulated by the presence of NTP-exposed J-Lat cells. Furthermore, co-culture of NTP-exposed J-Lat cells with mature phagocytes did not modulate their antigen presentation to primary CD8+ T lymphocytes (cross-presentation). However, reactivation from latency was stimulated in a clone-specific manner by NTP. Overall, these studies, which demonstrated that ex vivo application of NTP to latently infected lymphocytes can stimulate key immune cell responses, advance the development of an NTP-based immunotherapy that will provide ART-free control of HIV-1 reactivation in PLWH.
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The life expectancy of people living with HIV (PLWH) has greatly increased due to advancements in combination antiretroviral treatment (cART). However, this longer life has also increased the prevalence of age-related comorbidities, such as frailty, which now manifest sooner in this group. Frailty, a term coined by the insurance industry, has been broadened to include physical, cognitive, and emotional elements and has been recognized as a critical predictor of negative health outcomes. With the median age of PLWH now in the mid-50s, treating frailty is critical given its link to chronic diseases, cognitive decline, and even death. Frailty assessment tools, such as the Frailty Phenotype (FP) and the Frailty Index (FI), are used to identify vulnerable people. Understanding the pathophysiology of frailty in PLWH indicates the role of immunological mechanisms. Frailty screening and management in this group have progressed, with specialized clinics and programs concentrating on multidisciplinary care. Potential pharmacotherapeutic solutions, as well as novel e-health programs and sensors, are in the future of frailty treatment, but it is critical to ensure that frailty evaluation is not exploited to perpetuate ageist healthcare practices. This narrative review investigates the changing healthcare environment for older people living with HIV (OPLWH), notably in high-income countries. It emphasizes the significance of identifying and managing frailty as a crucial feature of OPLWH's holistic care and well-being.
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Longitudinal humoral immune response to inactivated COVID-19 vaccines among people living with HIV (PLWH) have not yet been systematically investigated. We conducted a 6-month longitudinal study among vaccinated PLWH and HIV-Negative Controls (HNC) to determine whether the humoral immune response effects of the inactivated COVID-19 vaccine are different between the two groups of people. Totally, 46 PLWH and 38 HNC who received the inactivated COVID-19 vaccine on days 0 and 28 were enrolled. The SARS-CoV-2 neutralizing antibodies (nAbs) and total specific IgM and IgG antibodies were examined on Day 0-Day190. The level and positive seroconversion rate of nAbs peaked on Day 42 in HNC while peaked on Day 70 in PLWH, then decreased gradually with the extension of the vaccination period after the peaks. The peak level of nAbs in PLWH on Day 70, (GMC 8.07 BAU/mL, 95% CI 5.67-11.48) was significantly lower than in HNC on Day 42 (GMC 18.28 BAU/mL, 95% CI 10.33-32.33, P =0.03). The decrease in the geometric mean concentrations (GMCs) of nAbs was observed as 42.9% in PLWH after peak level, which decreased from 8.07 BAU/mL [95% CI: 5.67-11.48] on Day 70 to 4.61 BAU/mL [95% CI: 3.35-6.34] on Day 190 (p = 0.02). On Day 190, only seven (18%, [95% CI: 6-40]) HNC and five (11%, [95% CI: 4-25]) PLWH maintained positive nAbs response respectively. The geometric mean ELISA units (GMEUs) and positive seroconversion rate of IgG in PLWH dropped significantly from Day 70 (GMEUs, 0.20 EU/mL, [95% CI: 0.13-0.34]; seroconversion, 52%, [95% CI: 34-69]) to Day 190 (GMEUs, 0.05 EU/mL, [95% CI: 0.03-0.08], P<0.001; seroconversion, 18%, [95% CI: 8-33], P<0.001). There was no significant difference in levels and seroconversion rates of nAbs and IgG between the two groups on Day 190. The peak immunogenicity of the inactivated COVID-19 vaccine was delayed and inferior in PLWH compared to HNC, while no significant difference was found in six-month immunogenicity between the two groups.
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COVID-19 , Infecciones por VIH , Humanos , Vacunas contra la COVID-19 , Inmunidad Humoral , Estudios Longitudinales , Vacunas de Productos Inactivados , SARS-CoV-2 , COVID-19/prevención & control , Anticuerpos Neutralizantes , Inmunoglobulina GRESUMEN
Much is known about the natural history of syphilis; however, less is known about the immune response against it, and even less is known about people living with HIV (PLWH). Due to the lack of an animal model to study host-pathogen interactions, it remains unclear how the host eliminates the bacteria. Here, we attempt to elucidate the immune response against infection by summarizing all the reported data in a systematic review. We found that only seven papers included PLWH, and they did not accurately describe the immune response against Treponema pallidum since only lymphopenia was reported upon coinfection. On the other hand, at least sixteen papers described the host-pathogen interaction in individual cell populations. Using this information, we established the kinetics of the immune response against syphilis and hypothesized how CD4+ T cells, such as Th17 and T rex cells, worsen the progression of the disease in PLWH through their hallmark cytokines, IL-10 and IL-17, and how these two cytokines may play important roles as biomarkers.
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Infecciones por VIH , Sífilis , Animales , Sífilis/microbiología , Interleucina-10 , Interleucina-17 , Citocinas , Biomarcadores , Infecciones por VIH/complicacionesRESUMEN
Thyroid diseases (TDs) and thyroid asymptomatic dysfunctions (TADs) are correlated with Human Immunodeficiency virus (HIV) infection and Acquired ImmunoDeficiency Syndrome (AIDS) as well as many endocrine dysfunctions and dysregulation of hormonal axes. To date, available studies on People Living With HIV (PLWH) affected by thyroid diseases and asymptomatic dysfunctions are few and rather controversial. The purpose of the present non-systematic literature review is to recap the current knowledge on the main features of thyroid dysfunctions and disorders in PLWH. Large cohort studies are needed for a better comprehension of the impact, evolution and treatment of thyroid pathologies in the HIV-infected population.