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1.
JNMA J Nepal Med Assoc ; 59(237): 486-489, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34508432

RESUMO

INTRODUCTION: Human Immunodeficiency Virus is a lentivirus that causes human immunodeficiency virus infection and over time, acquired immunodeficiency syndrome. Cluster of Differentiation 4+ T cell count of people living with this infection play a vital role to determine infection progression and necessary treatment changes. This study was conducted to find out the prevalence of low Cluster of Differentiation 4+ T Cell Count in the People Living with human immunodeficiency virus/ acquired immunodeficiency syndrome. METHODS: A descriptive cross-sectional study was conducted between June to August 2018 in the Human Immunodeficiency virus and Hepatitis Reference Unit of National Public Health Laboratory, Ministry of Health and Population Teku. Ethical approval was taken (Reference Number 2912) and a total of 550 seropositive cases of Human Immunodeficiency Virus-1 undergoing antiretroviral therapy were studied. Convenient sampling technique was used. Data was analysed by Statistical Package for the Social Sciences. RESULTS: Seventeen (3.1%) of patients had Cluster of Differentiation 4+ T cell counts below 100 cells/mm3 of blood. The mean Cluster of Differentiation 4+ T cell count was 509.3 cells/mm3 of blood. Of the total samples, 280 (50.9%) were males, 268 (48.7%) were females, and the rest 2 (0.4%) were of other gender. CONCLUSIONS: Majority of people living with human immunodeficiency virus/ acquired immunodeficiency syndrome were found immune-competent.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Contagem de Linfócito CD4 , Contagem de Células , Diferenciação Celular , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Laboratórios , Masculino
2.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479881

RESUMO

We report a case of a woman from Thailand, living in Malta, who was diagnosed with concomitant tuberculosis (TB) and HIV with depleted CD4 count. Her case was further complicated by the formation of a fistula between the mediastinal lymph nodes and the oesophagus, an unusual finding but for which she had many risk factors. The diagnosis was suspected on CT scan of the thorax and confirmed via upper gastrointestinal endoscopy. Following the commencement of both anti-TB and antiretroviral therapy, she suffered a lapse of immune reconstitution inflammatory syndrome but with aggressive medical management eventually made a full recovery without the need for surgical intervention.


Assuntos
Fístula , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Tuberculose , Contagem de Linfócito CD4 , Feminino , Fístula/diagnóstico por imagem , Fístula/etiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
3.
Shanghai Kou Qiang Yi Xue ; 30(3): 263-267, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476442

RESUMO

PURPOSE: To monitor oral candida infection and immune status of HIV/AIDS patients during the first year of highly active antiretroviral therapy (HAART), and to explore the relationship between oral candida infection and immune status. METHODS: A total of 46 HIV/AIDS patients were followed up. At baseline, 3, 6 and 12 months after HAART, CD4+T lymphocytes were measured, oral examinations of patients were carried out and the occurrence of oral candidiasis was recorded. Oral rinses were collected, and Sabourd's dextrose agar and CHROMagar candida medium were used to culture and identify oral candida. Statistical analysis was performed by SPSS 25.0 software package. RESULTS: The counts of CD4+T lymphocytes in HIV/AIDS patients at 3, 6 and 12 months after HAART were (327.91±138.82), (329.65±142.66) and (319.98±97.90) cells/mm3, respectively, which were significantly higher than CD4+T lymphocytes(263.39±126.01) at baseline(P<0.05). The prevalence of oral candidiasis at 3, 6 and 12 months after HAART was 26.09%, 21.74% and 23.91%, respectively, which was significantly lower than that(52.17%) at baseline(P<0.05). The prevalence of oral candidiasis in patients with CD4+T lymphocyte <200 cells/mm3 was significantly higher than that in patients with CD4+T lymphocyte ≥200 cells/mm3(P<0.05). CONCLUSIONS: HAART can increase CD4+T lymphocytes, reconstruct the immunity of patients and reduce the incidence of oral candidiasis, but the incidence of oral candidiasis significantly increased in patients with CD4+T lymphocyte <200 cells/mm3 .


Assuntos
Síndrome de Imunodeficiência Adquirida , Candidíase Bucal , Infecções por HIV , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos
4.
Afr Health Sci ; 21(Suppl): 1-7, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34447417

RESUMO

Background: Limited data is available on the treatment outcomes of HIV infected adolescents and young adults (AYA) in sub-Saharan Africa. HIV-infected adolescents and young adults (AYA) are at high risk of developing antiretroviral treatment failure. Objective: To determine the clinical, immunological and virologic outcomes of AYA at a tertiary hospital in Kenya. Methodology: A longitudinal study was conducted among AYA age 10-24 years attending Kenyatta National Hospital comprehensive care center. Clinical data was abstracted from electronic medical records for study participants with at least 6 months of follow-up using a structured data abstraction sheet. Results: A total of 250 AYA age 10 to 24 years were included. The median age was 16 years. The median CD4 cell count was 650.6 cells/mm3 (IQR 350.7-884.0). More than half (60.6%) of AYA had a CD4 cell count higher than 500 cells/mm3. Overall, 76.9% of AYA had achieved viral suppression (viral load <1000 copies/ml). There was a significant increase in virologic failure with higher age and late adolescents and young adults were more likely to have a viral load > 1000 copies/ml p<0.012. Conclusion: The overall virologic suppression in this cohort of AYA was sub-optimal. Both immunological and virologic outcomes were worse among late adolescents (18-19 years) and young adults (20-24 years).


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Adolescente , Contagem de Linfócito CD4 , Criança , Estudos Transversais , Feminino , Humanos , Quênia , Estudos Longitudinais , Masculino , Resultado do Tratamento , Carga Viral , Adulto Jovem
5.
Euro Surveill ; 26(33)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34414881

RESUMO

BackgroundThe assumption that migrants acquire human immunodeficiency virus (HIV) before migration, particularly those from high prevalence areas, is common.AimWe assessed the place of HIV acquisition of migrants diagnosed in four European countries using surveillance data.MethodsUsing CD4+ T-cell count trajectories modelled to account for seroconversion bias, we estimated infection year of newly HIV-diagnosed migrants residing in the United Kingdom (UK), Belgium, Sweden and Italy with a known arrival year and CD4+ T-cell count at diagnosis. Multivariate analyses identified predictors for post-migration acquisition.ResultsBetween 2007 and 2016, migrants constituted 56% of people newly diagnosed with HIV in the UK, 62% in Belgium, 72% in Sweden and 29% in Italy. Of 23,595 migrants included, 60% were born in Africa and 70% acquired HIV heterosexually. An estimated 9,400 migrants (40%; interquartile range (IQR): 34-59) probably acquired HIV post-migration. This proportion was similar by risk group, sex and region of birth. Time since migration was a strong predictor of post-migration HIV acquisition: 91% (IQR: 87-95) among those arriving 10 or more years prior to diagnosis; 30% (IQR: 21-37) among those 1-5 years prior. Younger age at arrival was a predictor: 15-18 years (81%; IQR: 74-86), 19-25 years (53%; IQR: 45-63), 26-35 years (37%; IQR: 30-46) and 36 years and older (25%; IQR: 21-33).ConclusionsMigrants, regardless of origin, sex and exposure to HIV are at risk of acquiring HIV post-migration to Europe. Alongside accessible HIV testing, prevention activities must target migrant communities.


Assuntos
Infecções por HIV , Migrantes , Contagem de Linfócito CD4 , Europa (Continente)/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Fatores de Risco
6.
Clin Immunol ; 230: 108824, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391936

RESUMO

The current intersection of the COVID-19 and HIV-1 pandemics, has raised concerns about the risk for poor COVID-19 outcomes particularly in regions like sub-Saharan Africa, disproportionally affected by HIV. DPP4/CD26 has been suggested to be a potential therapeutic target and a biomarker for risk in COVID-19 patients with high risk co-morbidities. We therefore evaluated soluble DPP4 (sDPP4) levels and activity in plasma of 131 HIV-infected and 20 HIV-uninfected South African individuals. Flow cytometry was performed to compare cell surface expression of DPP4/CD26 and activation markers on peripheral blood mononuclear cells of extreme clinical phenotypes. Progressors had lower specific DPP4 activity and lower frequency of CD3+ T-cells expressing CD26 than HIV-1 controllers, but more activated CD3+CD26+ T-cells. The frequency of CD26-expressing T-cells negatively correlated with HLA-DR+ and CD38+ T-cells. Divergent DPP4/CD26 expression between HIV-1 controllers and progressors may have implications for risk and treatment of COVID-19 in people living with HIV.


Assuntos
COVID-19/complicações , Dipeptidil Peptidase 4/metabolismo , Infecções por HIV/complicações , HIV-1 , SARS-CoV-2 , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Fatores de Risco , África do Sul , Carga Viral , Adulto Jovem
7.
J Acquir Immune Defic Syndr ; 88(1): 1-5, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397741

RESUMO

BACKGROUND: Understanding the attributes of COVID-19 clinical severity among people living with HIV (PLWH) compared with those in HIV-uninfected patients is critical for risk stratification and treatment strategies. METHODS: We conducted a retrospective study at Kaiser Permanente Southern California among PLWH aged 18 years or older. We compared the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization among PLWH and HIV-uninfected adults. A chart review was conducted for PLWH with COVID-19 to examine viral suppression of HIV and most recent CD4+ counts in the year before COVID-19 diagnosis, known exposures to COVID-19, and clinical presentation. RESULTS: Between March 1, 2020, and May 31, 2020, the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization was 551.2, 57.0, and 9.3 per 10,000 PLWH, respectively, compared with 268.4, 34.6, and 5.3 per 10,000 HIV-uninfected individuals, respectively. Among those with COVID-19, the distribution of race/ethnicity, smoking status, and comorbidities was similar in PLWH and HIV-uninfected patients; however, PLWH were mostly men, younger, and less obese than HIV-uninfected individuals. Health care utilization regarding emergency care and hospitalizations in the year before COVID-19-related hospitalization was similar between the groups. Overall, HIV was virologically suppressed in >95% of PLWH with COVID-19, and HIV viral load and CD4+ status did not differ between hospitalized and nonhospitalized patients. CONCLUSIONS: In this population of patients with well-controlled HIV infection, the incidence of testing, diagnosis, and hospitalization for COVID-19 was higher in PLWH than that in HIV-uninfected patients.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/virologia , Infecções por HIV/epidemiologia , Adolescente , Adulto , Contagem de Linfócito CD4 , COVID-19/epidemiologia , COVID-19/terapia , California/epidemiologia , Comorbidade , Prestação Integrada de Cuidados de Saúde , Feminino , Infecções por HIV/patologia , Infecções por HIV/terapia , Infecções por HIV/virologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Carga Viral , Adulto Jovem
9.
Pan Afr Med J ; 38: 370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367449

RESUMO

Introduction: highly active antiretroviral therapy (HAART) has contributed to a reduction in HIV- related oral lesions and improved quality of life among HIV seropositive patients. However, the therapy is not without its side effects. This study was aimed at assessing the self- reported orofacial manifestations due to long term use of HAART, as well as the pattern of oral lesions on examination. Methods: this was a cross-sectional study conducted among HIV seropositive adult patients in Ibadan, who had been on HAART for at least two years. Data were collected using an interviewer-administered questionnaire. Clinical diagnosis of HIV-related oral lesions was made according to the EC-Clearinghouse criteria. Data analysis was done using SPSS version 25. Results: the study participants comprised of 227 HIV seropositive patients who were HAART experienced, with 54 (24%) males and 173 (76%) females. Their mean age (±SD) was 44.7 (±9.4) years. The participants CD4 count ranged from 13-1338cells/mm3, with a median count of 341 cells/mm3. About half (45%) of the participants noted one or more orofacial changes since they commenced HAART. These oral changes included dryness of mouth, burning sensation, abnormal taste, melanotic hyperpigmentation, oral thrush, ulcers, and parotid swelling. Most of those who reported oral changes had been on HAART over 10 years (p=0.03), and the changes were more reported among those on the first-line regimen. Conclusion: melanotic hyperpigmentation was the most common oral lesion found and burning mouth syndrome was the most commonly reported complain among HIV-seropositive adults who are on long-term HAART.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Doenças da Boca/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/patologia , Nigéria , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
10.
Am J Case Rep ; 22: e932467, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379615

RESUMO

BACKGROUND Neurosyphilis is a bacterial infection of the brain and the spinal cord, caused by Treponema pallidum. Its nonspecific clinical presentation includes cognitive impairment and motor and/or sensory function compromise. Neurosyphilis infections in patients with HIV have increased over the past few years and many cases of neurosyphilis manifest in patients with HIV who have low CD4 T-cell counts and high viral loads (VL). However, there is extremely limited acknowledgement in the literature about neurosyphilis presentations in patients with HIV who have normal CD4 counts. CASE REPORT We present a neurosyphilis and HIV coinfection in a patient with a normal CD4 count and an undetectable VL. A 69-year-old woman with a medical history of HIV was on a prescribed antiretroviral treatment regimen. She presented in the Emergency Room in an unresponsive state, although this had been preceded by a period of rapidly progressive cognitive decline. Her brain computed tomography scan without contrast was unremarkable. Laboratory test results were within normal limits, except for a positive result for the microhemagglutination assay for Treponema pallidum antibodies and rapid plasma regain (RPR) test, which was highly suggestive of neurosyphilis as a presumed diagnosis. She showed remarkable clinical improvement after the initiation of conventional treatment for neurosyphilis, which is a 14-day regimen of intravenous penicillin G. CONCLUSIONS Given the broad neurological manifestations of neurosyphilis and its increasing incidence in patients with HIV, it is important to consider neurosyphilis in the differential diagnosis after ruling out other causes of encephalopathy, especially in patients with an undetectable VL and a normal CD4 count.


Assuntos
Infecções por HIV , Neurossífilis , Idoso , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Humanos , Neurossífilis/complicações , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico , Penicilinas , Carga Viral
11.
J Clin Lab Anal ; 35(9): e23923, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34390043

RESUMO

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.


Assuntos
COVID-19/virologia , Fezes/virologia , SARS-CoV-2/fisiologia , Eliminação de Partículas Virais/fisiologia , Adulto , Animais , Antivirais/administração & dosagem , Contagem de Linfócito CD4 , COVID-19/epidemiologia , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Cloroquina/análogos & derivados , Feminino , Humanos , Células Matadoras Naturais , Estudos Longitudinais , Lopinavir/administração & dosagem , Lynx , Masculino , Obesidade/epidemiologia , Sistema Respiratório/virologia , Estudos Retrospectivos , Fatores de Risco , Ritonavir/administração & dosagem , Fatores de Tempo , Eliminação de Partículas Virais/efeitos dos fármacos
13.
BMC Infect Dis ; 21(1): 731, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340689

RESUMO

BACKGROUND: Children living with human immunodeficiency virus (HIV) infection require lifelong effective antiretroviral therapy (ART). The goal of ART in HIV-infected persons is sustained viral suppression. There is limited information on virological non-suppression or failure and its associated factors in children in resource limited countries, particularly Ghana. METHODS: A cross-sectional study of 250 children aged 8 months to 15 years who had been on ART for at least 6 months attending the Paediatric HIV clinic at Korle Bu Teaching hospital in Ghana was performed. Socio-demographic, clinical, laboratory and ART Adherence related data were collected using questionnaires as well as medical records review. Blood samples were obtained for viral load and CD4+ count determination. Viral load levels > 1000 copies/ml on ART was considered virological non-suppression. Logistic regression was used to identify factors associated with virological non-suppression. RESULTS: The mean (±SD) age of the study participants was 11.4 ± 2.4 years and the proportion of males was 53.2%. Of the 250 study participants, 96 (38.4%) had virological non-suppression. After adjustment for significant variables, the factors associated with non-suppressed viral load were female gender (AOR 2.51 [95% CI 1.04-6.07], p = 0.041), having a previous history of treatment of tuberculosis (AOR 4.95 [95% CI 1.58-15.5], p = 0.006), severe CD4 immune suppression status at study recruitment (AOR 24.93 [95% CI 4.92-126.31], p < 0.001) and being on a nevirapine (NVP) based regimen (AOR 7.93 [95% CI 1.58-1.15], p = 0.005). CONCLUSION: The prevelance of virological non-suppression was high. Virological non-suppression was associated with a previous history of TB treatment, female gender, severe CD4 immune suppression status at study recruitment and being on a NVP based regimen. Early initiation of ART and phasing out NVP-based regimen might improve viral load suppression in children. In addition, children with a history of TB may need focused measures to maximize virological suppression.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos Transversais , Feminino , Gana , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Lactente , Modelos Logísticos , Masculino , Nevirapina/uso terapêutico , Fatores de Risco , Fatores Sexuais , Falha de Tratamento , Tuberculose/complicações , Carga Viral
14.
AIDS Res Ther ; 18(1): 50, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372879

RESUMO

BACKGROUND: There is a growing recognition of the impact of gender and the social determinants of health on the clinical course of people living with HIV (PLHIV). However, the relative contribution of these factors to clinical outcomes of PLHIV is incompletely defined in many countries. This study was performed to gain a greater understanding of the non-clinical determinants of prognosis of PLHIV in Myanmar. METHODS: Selected demographic, behavioural and socioeconomic characteristics of outpatients at two specialist HIV hospitals and one general hospital in Yangon, Myanmar were correlated with their subsequent clinical course; a poor outcome was defined as death, hospitalisation, loss to follow-up or a detectable viral load at 6 months of follow-up. RESULTS: 221 consecutive individuals with advanced HIV commencing anti-retroviral therapy (ART) were enrolled in the study; their median CD4 T-cell count was 92 (44-158) cells/mm3, 138 (62.4%) were male. Socioeconomic disadvantage was common: the median (interquartile range (IQR) monthly per-capita income in the cohort was US$48 (31-77); 153 (69.9%) had not completed high school. However, in a multivariate analysis that considered demographic, behavioural, clinical factors and social determinants of health, male gender was the only predictor of a poor outcome: odds ratio (95% confidence interval): 2.33 (1.26-4.32, p = 0.007). All eight of the deaths and hospitalisations in the cohort occurred in males (p = 0.03). CONCLUSIONS: Men starting ART in Myanmar have a poorer prognosis than women. Expanded implementation of gender-specific management strategies is likely to be necessary to improve outcomes.


Assuntos
Infecções por HIV , Determinantes Sociais da Saúde , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Mianmar/epidemiologia , Carga Viral
15.
Arterioscler Thromb Vasc Biol ; 41(9): 2387-2398, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34320835

RESUMO

Objective: CD4 T cells are important regulators of atherosclerotic progression. The metabolic profile of CD4 T cells controls their signaling and function, but how atherosclerosis affects T-cell metabolism is unknown. Here, we sought to determine the impact of atherosclerosis on CD4 T-cell metabolism and the contribution of such metabolic alterations to atheroprogression. Approach and Results: Using PCR arrays, we profiled the expression of metabolism genes in CD4 T cells from atherosclerotic apolipoprotein-E knockout mice fed a Western diet. These cells exhibited dysregulated expression of genes critically involved in glycolysis and fatty acid degradation, compared with those from animals fed a standard laboratory diet. We examined how T-cell metabolism was changed in either Western diet­fed apolipoprotein-E knockout mice or samples from patients with cardiovascular disease by measuring glucose uptake, activation, and proliferation in CD4 T cells. We found that naive CD4 T cells from Western diet­fed apolipoprotein-E knockout mice failed to uptake glucose and displayed impaired proliferation and activation, compared with CD4 T cells from standard laboratory diet­fed animals. Similarly, we observed that naive CD4 T-cell frequencies were reduced in the circulation of human subjects with high cardiovascular disease compared with low cardiovascular disease. Naive T cells from high cardiovascular disease subjects also showed reduced proliferative capacity. Conclusions: These results highlight the dysfunction that occurs in CD4 T-cell metabolism and immune responses during atherosclerosis. Targeting metabolic pathways within naive CD4 T cells could thus yield novel therapeutic approaches for improving CD4 T-cell responses against atheroprogression.


Assuntos
Aterosclerose/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Glicólise , Placa Aterosclerótica , Idoso , Animais , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Células Cultivadas , Dieta Ocidental , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica , Glicólise/genética , Humanos , Ativação Linfocitária , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Oxirredução , Fenótipo
16.
Emerg Med Pract ; 23(7): 1-24, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34196515

RESUMO

As highly active antiretroviral therapies have advanced, HIV patients who are treatment-adherent can achieve undetectable viral loads, virtual elimination of opportunistic infection, improved quality of life, and normal life expectancy. This issue focuses on emergency department management of HIV patients both with successful disease suppression from long-term therapy as well as the patient with low CD4 counts in the context of lack of engagement with care, nonadherence, or undiagnosed disease. Optimal emergency department management of patients with HIV also includes identifying and treating undiagnosed patients, helping to re-establish care for those who have been lost to followup, and preventing new HIV infections with pre-exposure and postexposure prophylaxis.


Assuntos
Serviço Hospitalar de Emergência , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Adulto , Contagem de Linfócito CD4 , Humanos , Cooperação do Paciente , Profilaxia Pós-Exposição , Profilaxia Pré-Exposição
17.
Lancet Child Adolesc Health ; 5(9): 642-651, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34302760

RESUMO

BACKGROUND: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. METHODS: In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per µL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. INTERPRETATION: In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. FUNDING: Gilead Sciences.


Assuntos
Alanina , Antirretrovirais , Monitoramento de Medicamentos/métodos , Emtricitabina , Infecções por HIV , Tenofovir/análogos & derivados , Adolescente , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/farmacocinética , Amidas/administração & dosagem , Amidas/efeitos adversos , Amidas/farmacocinética , Antirretrovirais/administração & dosagem , Antirretrovirais/efeitos adversos , Antirretrovirais/farmacocinética , Contagem de Linfócito CD4/métodos , Criança , Cálculos da Dosagem de Medicamento , Quimioterapia Combinada/métodos , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Emtricitabina/farmacocinética , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Humanos , Masculino , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Piridonas/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/farmacocinética , Resultado do Tratamento , Carga Viral/métodos
18.
AIDS ; 35(10): 1537-1548, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34270487

RESUMO

OBJECTIVE: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. DESIGN: Longitudinal cohort study. METHODS: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events. RESULTS: Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viraemia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to ≥5000 copies/ml was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression. CONCLUSIONS: As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viraemia who remain at low risk of disease progression.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , África ao Sul do Saara , Fármacos Anti-HIV/uso terapêutico , Biomarcadores , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Longitudinais , Uganda/epidemiologia , Carga Viral , Viremia/tratamento farmacológico
19.
BMC Pediatr ; 21(1): 315, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261465

RESUMO

BACKGROUND: HIV testing and treatment guidelines for children in sub-Saharan Africa have evolved over time, such that children are now treated at younger ages. The objective of this study was to describe the treatment experience for immunologic, virologic, and growth outcomes among HIV-infected Zambian children younger than 5 years of age from 2008 to 2018. METHODS: Participants enrolled in a clinical cohort study in Macha, Zambia and initiating antiretroviral treatment before 5 years of age between 2008 and 2015 were included in the analysis and followed up to the end of 2018. Outcomes, including growth, CD4+ T-cell percentage, viral suppression, and mortality, were evaluated among all children using longitudinal and survival analyses. Comparisons by age at treatment initiation (< 1, 1 to < 2, and 2 to < 5 years) were also evaluated. RESULTS: Three hundred eighty-one children initiating treatment before 5 years of age between 2008 and 2015 were included in the analysis. Growth metrics and CD4+ T-cell percentage improved over time after treatment initiation. However, 20% of children remained underweight and 40% of children remained stunted after the first 36 months of treatment. 85% of children had a viral load < 400 copies/mL after 12 months of treatment. However, children < 1 year at treatment initiation were more likely to have a detectable viral load in the first 12 months of treatment and less likely to achieve viral suppression compared to older children. Mortality was highest in the first 12 months of treatment, among underweight children, and among children initiating treatment in 2008-2010 compared to 2011-2015. CONCLUSIONS: Most children initiating antiretroviral treatment from 2008 to 2015 in rural Zambia responded well to treatment. However, many children remained underweight and stunted, and experienced high mortality rates during the first few months of treatment. This supports continued efforts to improve early infant diagnosis, nutritional support, and pediatric drug formulations.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Criança , Estudos de Coortes , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Resultado do Tratamento , Carga Viral , Zâmbia/epidemiologia
20.
J Med Case Rep ; 15(1): 341, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34243803

RESUMO

INTRODUCTION: Since its debut recognition in 1981, human immunodeficiency virus/acquired immunodeficiency syndrome has affected over 77 million people and has resulted in premature cessation of 35.4 million lives worldwide. Commonly, human immunodeficiency virus is transmitted by sexual contact across mucosal surfaces, by sharing of injecting equipment, through contaminated blood transfusions, and by maternal-infant exposure. Nevertheless, accidental transmission incidences involving family members are rare but possible. CASE PRESENTATION: A 78-year-old woman of African descent from Mtwara Region south of Tanzania was referred to us for further evaluation and treatment. She is 30 years postmenopausal and has a 35-year history of hypertension. Her last attendance to our institute was 11 months prior the index visit and she tested negative for human immunodeficiency virus. She came with complaints of weight loss, recurrent fevers, and cough. Her hematological tests revealed leukopenia with lymphocytosis, together with a normocytic normochromic anemia. Enzyme-linked immunosorbent assay for human immunodeficiency virus was positive, and she had a CD4 count of 177 cells/µL. We went back to history taking to identify the potential source of infection. We were informed that for the past 6 months, the 78-year-old lady has been living with her unwell 24-year-old granddaughter who has been divorced. The granddaughter had a history of recurrent fevers, significant weight loss, and a suppurative skin condition. As a way to show love and care, the old lady was puncturing the suppurative lesions with bare hands; then she would suck them to clear away the discharge. We requested to see the young lady, and she tested positive for human immunodeficiency virus. Both were started on tenofovir/lamivudine/dolutegravir combination plus cotrimoxazole 960 mg. The family was in total disarray following these findings. The patient was discharged through infectious diseases department and died of Pneumocystis jirovecii pneumonia 12 weeks later. CONCLUSIONS: Certain sociocultural norms that are believed to express love, care, and togetherness in developing rural communities, particularly Sub-Saharan Africa, have a potential of spreading human immunodeficiency virus, thus warranting prompt transformation.


Assuntos
Avós , Infecções por HIV , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tanzânia , Adulto Jovem
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