RESUMO
Since its first appearance in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world and has become a global pandemic. Several medical comorbidities have been identified as risk factors for coronavirus disease 2019 (COVID-19). However, it remains unclear whether people living with human immunodefeciency virus (PLWH) are at an increased risk of COVID-19 and severe disease manifestation, with controversial suggestion that HIV-infected individuals could be protected from severe COVID-19 by means of antiretroviral therapy or HIV-related immunosuppression. Several cases of coinfection with HIV and SARS-CoV-2 have been reported from different parts of the globe. This review seeks to provide a holistic overview of SARS-CoV-2 infection in PLWH.
Assuntos
Fármacos Anti-HIV/uso terapêutico , COVID-19/epidemiologia , Infecções por HIV/epidemiologia , Hospedeiro Imunocomprometido , Pandemias , SARS-CoV-2/patogenicidade , Adulto , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Coinfecção , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.
Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/química , Antivirais/classificação , Antivirais/isolamento & purificação , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Descoberta de Drogas , HIV/efeitos dos fármacos , HIV/patogenicidade , HIV/fisiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepacivirus/fisiologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Herpes Simples/patologia , Herpes Simples/virologia , Humanos , Influenza Humana/patologia , Influenza Humana/virologia , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Orthomyxoviridae/fisiologia , Pandemias , Compostos Fitoquímicos/química , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Plantas Medicinais , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SARS-CoV-2 , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidade , Simplexvirus/fisiologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
RESUMEN El linfoma de Burkitt, se trata de un subtipo poco frecuente del linfoma no Hodgkin, con elevada frecuencia en aquellos pacientes con sida. La hepatoesplenomegalia es un signo clínico de gran importancia para el diagnóstico oportuno de algunas patologías; entre los mecanismos de formación de la hepatoesplenomegalia se encuentra la infiltración celular, ocasionada por la migración de células tumorales. Se presenta por inflamaciones debido a la presencia de infecciones por virus o bacterias las cuales son muy comunes en pacientes con sida. Se presentó un caso de un paciente masculino de 4 años, diagnosticado con VIH positivo, con la configuración correspondiente de criterios clínicos en clasificación C para sida. El cual desarrolló a nivel de cavidad oral un Burkitt primario, que se acompañó de hepatoesplenomegalia. Se pretendió describir la relación y el comportamiento de este tipo de linfoma con la hepatoesplenomegalia, así como la repercusión a nivel del sistema estomatognático, a nivel sistémico y el plan de tratamiento. Por el cuadro clínico e inmunológico del paciente estudiado, se planteó un pronóstico reservado por presentar un cuadro clínico infrecuente, en el que se observó Burkitt; tanto a nivel del sistema estomatognático como a nivel abdominal. Se hizo necesario realizar un diagnóstico oportuno y certero para iniciar el tratamiento a tiempo, se comenzó inmediatamente con tratamiento (AU).
ABSTRACT Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin lymphoma, with high frequency in those patients with AIDS. Hepatosplenomegaly is a clinical sign of great importance for the timely diagnosis of some pathologies; cellular infiltration is found among the mechanisms of hepatosplenomegaly formation; it is caused by the migration of tumor cells. It emerges by inflammations due to the presence of infections by virus or bacteria which are very common in patients with AIDS. The authors present the case of a male patient, aged 4 years, with a positive HIV diagnosis, and the correspondent configuration of clinical criteria in C classification for AIDS, who developed a primary Burkitt lymphoma at the level of oral cavity We present the case of a 4-year-old male patient diagnosed with HIV positive, with the corresponding configuration of clinical criteria in classification C for AIDS; who developed a primary LB at the oral cavity level that was accompanied by hepatosplenomegaly. The authors pretended to describe the relation and behavior of this kind of lymphoma with hepatosplenomegaly, and also the repercussion at the stomatognathic level, at the systemic level and the treatment plan. Due to the clinical and immunological characteristics of the studied patient a reserved prognosis was given because of presenting infrequent clinical characteristics in which a Burkitt was observed both, at the stomatognathic and at the abdominal level. It was necessary to make an opportune and accurate diagnosis to begin the treatment on time (AU).
Assuntos
Humanos , Masculino , Criança , Sinais e Sintomas , Criança , Linfoma de Burkitt/complicações , Esplenomegalia/complicações , Esplenomegalia/diagnóstico , Neoplasias Bucais/complicações , Neoplasias Bucais/diagnóstico , Antígenos HIV/uso terapêutico , Diagnóstico Clínico/diagnóstico , HIV/patogenicidade , Hepatomegalia/diagnósticoRESUMO
BACKGROUND: The impact of nutritional supplements on weight gain in HIV-infected children on antiretroviral treatment (ART) remains uncertain. Starting supplements depends upon current weight-for-age or other acute malnutrition indicators, producing time-dependent confounding. However, weight-for-age at ART initiation may affect subsequent weight gain, independent of supplement use. Implications for marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) are unclear. METHODS: In the ARROW trial, non-randomised supplement use and weight-for-age were recorded monthly from ART initiation. The effect of supplements on weight-for-age over the first year was estimated using generalised estimating equation MSMs with IPTW, both with and without interaction terms between baseline weight-for-age and time. Separately, data were simulated assuming no supplement effect, with use depending on current weight-for-age, and weight-for-age trajectory depending on baseline weight-for-age to investigate potential bias associated with different MSM specifications. RESULTS: In simulations, despite correctly specifying IPTW, omitting an interaction in the MSM between baseline weight-for-age and time produced increasingly biased estimates as associations between baseline weight-for-age and subsequent weight trajectory increased. Estimates were unbiased when the interaction between baseline weight-for-age and time was included, even if the data were simulated with no such interaction. In ARROW, without an interaction the estimated effect was +0.09 (95%CI +0.02,+0.16) greater weight-for-age gain per month's supplement use; this reduced to +0.03 (-0.04,+0.10) including the interaction. DISCUSSION: This study highlights a specific situation in which MSM model misspecification can occur and impact the resulting estimate. Since an interaction in the MSM (outcome) model does not bias the estimate of effect if the interaction does not exist, it may be advisable to include such a term when fitting MSMs for repeated measures.
Assuntos
Infecções por HIV/dietoterapia , Apoio Nutricional/métodos , Aumento de Peso/efeitos dos fármacos , Antirretrovirais/uso terapêutico , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Pré-Escolar , Suplementos Nutricionais/análise , Feminino , HIV/patogenicidade , Infecções por HIV/metabolismo , Humanos , Lactente , Masculino , Modelos Estatísticos , Modelagem Computacional Específica para o Paciente , Projetos de PesquisaRESUMO
We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.
Assuntos
Atrofia/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Infecções por HIV/diagnóstico por imagem , Neuralgia/diagnóstico por imagem , Parestesia/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Adulto , Idoso , Atrofia/patologia , Atrofia/virologia , Mapeamento Encefálico , Estudos Transversais , Feminino , Giro do Cíngulo/patologia , Giro do Cíngulo/virologia , HIV/patogenicidade , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuralgia/patologia , Neuralgia/virologia , Parestesia/patologia , Parestesia/virologia , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/virologia , Tálamo/patologia , Tálamo/virologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/virologiaRESUMO
BACKGROUND: The authors present a case of a 66-year-old male who was diagnosed with human immunodeficiency virus, and his medical course of highly active antiretroviral therapy was complicated with the development of immune reconstitution inflammatory syndrome, which led to development of movement disorder consisting of right-sided resting tremor, neck dystonia, and jaw clenching. CASE DESCRIPTION: The patient's symptoms resembled that of rubral tremor, and he underwent placement of a deep brain stimulation electrode into the left ventral intermediate nucleus of the thalamus with significant improvement of symptoms. CONCLUSIONS: This is the first reported case in the literature of a human immunodeficiency virus-positive patient's treatment course complicated with immune reconstitution inflammatory syndrome with neurologic manifestation, which was refractory to medical therapy and thus treated with deep brain stimulation.
Assuntos
Estimulação Encefálica Profunda , HIV/patogenicidade , Síndrome Inflamatória da Reconstituição Imune/terapia , Tremor/virologia , Idoso , Ataxia/terapia , Ataxia/virologia , Estimulação Encefálica Profunda/efeitos adversos , Humanos , Síndrome Inflamatória da Reconstituição Imune/complicações , Síndrome Inflamatória da Reconstituição Imune/virologia , Masculino , Tálamo/cirurgia , Tálamo/virologia , Tremor/diagnóstico , Tremor/etiologia , Tremor/cirurgiaRESUMO
The purpose of this study was to assess whole brain and regional patterns of cerebrovascular reactivity (CVR) abnormalities in HIV-infected women using quantitative whole brain arterial spin labeling (ASL). We hypothesized that HIV-infected women would demonstrate decreased regional brain CVR despite viral suppression. This cross-sectional study recruited subjects from the Bay Area Women's Interagency Health Study (WIHS)-a cohort study designed to investigate the progression of HIV disease in women. In addition to conventional noncontrast cerebral MRI sequences, perfusion imaging was performed before and after the administration of intravenous acetazolamide. CVR was measured by comparing quantitative ASL brain perfusion before and after administration of intravenous acetazolamide. In order to validate and corroborate ASL-based whole brain and regional perfusion, phase-contrast (PC) imaging was also performed through the major neck vessels. FLAIR and susceptibility weighted sequences were performed to assess for white matter injury and microbleeds, respectively. Ten HIV-infected women and seven uninfected, age-matched controls were evaluated. Significant group differences were present in whole brain and regional CVR between HIV-infected and uninfected women. These regional differences were significant in the frontal lobe and basal ganglia. CVR measurements were not significantly impacted by the degree of white matter signal abnormality or presence of microbleeds. Despite complete viral suppression, dysfunction of the neurovascular unit persists in the HIV population. Given the lack of association between CVR and traditional imaging markers of small vessel disease, CVR quantification may provide an early biomarker of pre-morbid vascular disease.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Gânglios da Base/patologia , Artérias Cerebrais/patologia , Transtornos Cerebrovasculares/patologia , Lobo Frontal/patologia , Infecções por HIV/patologia , Substância Branca/patologia , Acetazolamida/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Gânglios da Base/irrigação sanguínea , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/virologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/virologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/tratamento farmacológico , Estudos Transversais , Progressão da Doença , Feminino , Lobo Frontal/irrigação sanguínea , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/virologia , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Humanos , Angiografia por Ressonância Magnética/métodos , Pessoa de Meia-Idade , RNA Viral/genética , Marcadores de Spin , Substância Branca/irrigação sanguínea , Substância Branca/diagnóstico por imagem , Substância Branca/virologiaRESUMO
Physical exercise is a common type of planned physical activity in order to enhance or maintain a person's physical fitness. Physical exercise may act as an effective strategy to take control of certain conditions associated with HIV-1 infection. HIV infection and its related treatments not only affect the immune system but also cause several musculoskeletal disorders including pre-sarcopenia or sarcopenia, myalgia, and low bone mineral density. Moderate- to high-intensity aerobic exercise, progressive resistance exercise, or a combination of both is considered as a complementary part of medical care and treatment of HIV-infected individuals. In the present chapter, the results of recent investigations regarding the effects of physical activity on muscle strength and function, mental health, and immune system of HIV infected individuals will be discussed.
Assuntos
Exercício Físico/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Saúde Mental , Qualidade de Vida , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/psicologia , Síndrome da Imunodeficiência Adquirida/terapia , HIV/imunologia , HIV/patogenicidade , Infecções por HIV/terapia , HumanosRESUMO
Unlike many vitamins derived predominantly from food sources, vitamin D is produced endogenously in the skin upon exposure to sunlight. Ethnicity, skin pigmentation, socioeconomic status, geographic location, climate and sunscreen; all of these factors contribute to the amount of insolation for any given individual. Insufficient insolation creates the prerequisites for vitamin D deficiency. This is particularly true in HIV-infected individuals, who are highly vulnerable to vitamin D insufficiency/deficiency, as it plays a huge role in the musculoskeletal and cardiovascular systems. Antiretroviral therapy may also be a factor in vitamin D deficiency. Today, as the issues of preventing common skeletal and non-skeletal diseases with HIV-infected people are becoming highly relevant, the maintenance of vitamin D levels through exposure to sunlight or supplementation appears to be an effective and safe solution. This review focuses on studies concerning the potential role of vitamin D supplementation through adequate sunlight exposure or dietary intake in HIV-infected people. The biology and epidemiology of HIV infection, as well as the issues related to vitamin D deficiency, its status on immune function, the effect of vitamin D against HIV disease progression and other health aspects of this vitamin, are briefly explained.
Assuntos
Suplementos Nutricionais , Infecções por HIV/terapia , Luz Solar , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , HIV/patogenicidade , Infecções por HIV/imunologia , HumanosRESUMO
BACKGROUND: Needlestick injury (NSI) is one of the most burdensome professional hazards in any medical setting; it can lead to transmission of fatal infectious diseases, such as hepatitis B, hepatitis C and human immunodeficiency virus. In the United States, the annual cost burden was estimated as somewhere between $118 million to $591 million; in the United Kingdom it is approximated to be £500,000 (US$919,117.65) per the National Health Service. METHOD: This is the first published paper on the national cost burden of NSIs in Japan. A systematic literature review was conducted to review previous study design in global studies and to extract parameter values from Japanese studies. We conducted abstract searches through PubMed and the Japan Medical Abstracts Society (Ichushi), together with grey literature and snowball searches. A simple economic model was developed to calculate cost burden of NSIs from a societal perspective over a one-year time horizon. We assumed all NSIs are reported and perfect adherence in post NSI management that presented in the labour compensation scheme. Local guidelines were also referenced to extract resource utilization. Lastly, a deterministic sensitivity analysis was conducted and a scenario analysis which considered a payer perspective was also included. RESULT AND CONCLUSION: The national cost burden of in-hospital NSIs is estimated as ¥33.4 billion (US$302 million) annually, based on an average cost per NSI of ¥63,711 (US$577) and number of NSIs at 525,000/year. 70% of the cost is due to initial laboratory tests, followed by productivity loss, estimated at 20% of the total cost. Cost of contaminated NSIs remains at 5% of the total cost. Change in number of NSIs significantly influences outcomes. Variation in post-exposure management practices suggests a need for NSI specific National guidelines and holistic labour compensation scheme development in Japan.
Assuntos
Pessoal de Saúde , Ferimentos Penetrantes Produzidos por Agulha/economia , Profilaxia Pós-Exposição/métodos , Medicina Estatal/economia , Custos e Análise de Custo , Feminino , HIV/patogenicidade , Hepacivirus/patogenicidade , Humanos , Japão/epidemiologia , Masculino , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Ferimentos Penetrantes Produzidos por Agulha/virologiaRESUMO
BACKGROUND: The global burden of cervical cancer remains high with the highest morbidity and mortality rates reported in developing countries. Hyperthermia as a chemo- and radiosensitiser has shown to improve treatment outcomes. This is an analysis of the local control results at six months post-treatment of patients enrolled in an ongoing study investigating the effects of the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for the treatment of HIV-positive and -negative cervical cancer patients in a low-resource setting. METHODS: This ongoing Phase III randomised controlled trial, conducted at a state hospital in Johannesburg, South Africa, was registered with the appropriate ethics committee. After signing an informed consent, participants with FIGO stages IIB to IIIB squamous cell carcinoma of the cervix were randomised to receive chemoradiotherapy with/without mEHT using a secure online random-sampling tool (stratum: HIV status) accounting for age and stage. Reporting physicians were blind to treatment allocation. HIV-positive participants on antiretroviral treatment, or with a CD4 count >200cell/µL were included. mEHT was administered 2/weekly immediately before external beam radiation. The primary end point is local disease control (LDC) and secondary endpoints are toxicity; quality of life analysis; and two year survival. We report on six month LDC, including nodes visualised in the radiation field on 18F-FDG PET/CT (censored for six month survival), and six month local disease free survival (LDFS) (based on intention to treat). Trial status: Recruitment closed (ClinicalTrials.gov: NCT03332069). RESULTS: 271 participants were recruited between January 2014 and November 2017, of which 210 were randomised for trial and 202 were available for analysis at six months post-treatment (mEHT: n = 101; Control: n = 101). Six month LDFS was higher in the mEHT Group (n = 39[38.6%]), than in the Control Group (n = 20[19.8%]); p = 0.003). LDC was also higher in the mEHT Group (n = 40[45.5%]) than the Control Group (n = 20[24.1%]); (p = 0.003). CONCLUSION: Our results show that mEHT is effective as a chemo-radiosensitiser for cervical cancer, even in high risk a patients and resource-constrained settings.
Assuntos
Quimiorradioterapia , Hipertermia Induzida/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , HIV/patogenicidade , Soropositividade para HIV/virologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
Human immunodeficiency virus/tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004-2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service. This is the first study to produce estimates of the impact of the ART rollout by exploiting staggered timing and geographic variation in the rollout. After ART became available in a health facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P < 0.0001) more received repeat testing; however, there was a steep rise in testing before the introduction of ART. Although the number of TB-positive patients increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among tested patients fell by 2 percentage points (8%, P = 0.001) after 2 years. Sputum smear testing declined relative to more technologically advanced diagnostics post-ART. Antiretroviral therapy availability increased the attention to TB screening and drew new patients into the health-care system. Small increases in the numbers of repeat patients are indicative of retention in care. The decline in TB rates post-ART suggests that the reduction in TB risk due to improved immune functioning and health-care contact likely outweighed the increased TB risk because of the longer lifespan of ART initiators.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Modelos Estatísticos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Coinfecção , Bases de Dados Factuais , Feminino , HIV/patogenicidade , HIV/fisiologia , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Masculino , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/fisiologia , Programas Nacionais de Saúde , Prevalência , África do Sul/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissãoRESUMO
PURPOSE OF REVIEW: Vitamin D (VitD) deficiency is highly prevalent among HIV-infected individuals. Given the overlapping risk for several chronic disease and immunomodulatory outcomes from both long-standing HIV and VitD deficiency, there is great interest in clarifying the clinical role of VitD for this population. RECENT FINDINGS: Recent studies have expanded our knowledge regarding the epidemiology and mechanisms of VitD deficiency-associated outcomes in the setting of HIV. Clinical trials focusing on VitD supplementation have demonstrated a positive impact on bone mineral density in subgroups of HIV-infected individuals initiating ART or on suppressive ART regimens; however, significant heterogeneity exists between studies and data are less consistent with other clinical outcomes. Further research is needed to clarify uncertainly in several domains, including identifying patients at greatest risk for poor outcomes from VitD deficiency, standardizing definitions and measurement techniques, and better quantifying the benefits and risks of VitD supplementation across different demographic strata for skeletal and extra-skeletal outcomes.
Assuntos
Densidade Óssea/efeitos dos fármacos , Infecções por HIV/complicações , Deficiência de Vitamina D , Vitamina D/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Suplementos Nutricionais , Feminino , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Risco , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/epidemiologiaRESUMO
BACKGROUND: Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. MATERIALS AND METHODS: Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by ß-hydroxylation of testosterone. RESULTS: Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4. CONCLUSION: Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic.
Assuntos
Bactérias/efeitos dos fármacos , Resina Mástique/farmacologia , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antivirais/química , Antivirais/farmacologia , Bactérias/patogenicidade , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP3A/genética , HIV/efeitos dos fármacos , HIV/patogenicidade , Hexanos/química , Humanos , Resina Mástique/química , Neoplasias/patologia , Pistacia/química , Extratos Vegetais/química , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidadeRESUMO
Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.
Assuntos
Substituição de Aminoácidos , Imagem de Tensor de Difusão/métodos , Infecções por HIV/diagnóstico por imagem , HIV/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/patologia , Núcleo Caudado/virologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Corpo Caloso/virologia , Imagem de Tensor de Difusão/instrumentação , Feminino , Expressão Gênica , Variação Genética , Genótipo , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/virologia , HIV/patogenicidade , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Putamen/diagnóstico por imagem , Putamen/patologia , Putamen/virologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Tálamo/virologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/virologiaRESUMO
HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups.
Assuntos
Terapia Antirretroviral de Alta Atividade , Ácidos Graxos Ômega-3/administração & dosagem , Infecções por HIV/dietoterapia , Estresse Oxidativo/efeitos dos fármacos , Adulto , Colesterol/metabolismo , Feminino , Glutationa/metabolismo , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Carga Viral/efeitos dos fármacosRESUMO
Theoretically, integration of vertically organized services is seen as an important approach to improving the efficiency of health service delivery. However, there is a dearth of evidence on the effect of integration on the technical efficiency of health service delivery. Furthermore, where technical efficiency has been assessed, there have been few attempts to incorporate quality measures within efficiency measurement models particularly in sub-Saharan African settings. This paper investigates the technical efficiency and the determinants of technical efficiency of integrated HIV and sexual and reproductive health (SRH) services using data collected from 40 health facilities in Kenya and Swaziland for 2008/2009 and 2010/2011. Incorporating a measure of quality, we estimate the technical efficiency of health facilities and explore the effect of integration and other environmental factors on technical efficiency using a two-stage semi-parametric double bootstrap approach. The empirical results reveal a high degree of inefficiency in the health facilities studied. The mean bias corrected technical efficiency scores taking quality into consideration varied between 22% and 65% depending on the data envelopment analysis (DEA) model specification. The number of additional HIV services in the maternal and child health unit, public ownership and facility type, have a positive and significant effect on technical efficiency. However, number of additional HIV and STI services provided in the same clinical room, proportion of clinical staff to overall staff, proportion of HIV services provided, and rural location had a negative and significant effect on technical efficiency. The low estimates of technical efficiency and mixed effects of the measures of integration on efficiency challenge the notion that integration of HIV and SRH services may substantially improve the technical efficiency of health facilities. The analysis of quality and efficiency as separate dimensions of performance suggest that efficiency may be achieved without sacrificing quality.
Assuntos
Prestação Integrada de Cuidados de Saúde/métodos , Prestação Integrada de Cuidados de Saúde/normas , Melhoria de Qualidade , Serviços de Saúde Reprodutiva/normas , Essuatíni , HIV/patogenicidade , Infecções por HIV , Humanos , Quênia , Comportamento SexualRESUMO
We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
Assuntos
Antivirais/farmacologia , Géis/administração & dosagem , Herpes Simples/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/patogenicidade , Acetato de Zinco/farmacologia , Animais , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Células CACO-2 , Candida albicans/efeitos dos fármacos , Carragenina/farmacologia , Chlorocebus aethiops , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 2/patogenicidade , Humanos , Lactobacillus/efeitos dos fármacos , Macaca mulatta , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Concentração Osmolar , Células Vero , Acetato de Zinco/administração & dosagemRESUMO
Two new tryptophan derivatives, N-sulfonyl-L-tryptophan (tryptorheedei A) (1) and 3-(N-sulfonylindolyl)-D-lactic acid (tryptorheedei B) (2) together with the known 5-O-ß-D-glucopyranosyl-2-hydroxyphenylacetic acid (3), 1-O-methylglucopyranoside, entadamide A, homogentisic acid and 3-O-ß-D-glucopyranosyl-ß-sitosterol, were isolated from the seed kernels of Entada rheedei (Mimosaceae). Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry and by comparison with spectroscopic data reported in the literature. Compounds 1 and 2 showed no toxicity to TZM and Human PBMC cells. Both compounds 1 and 2 were found to promote early infection events in HIV, likely by inhibiting the enzyme indolamine 2,3-dioxygenase (IDO) and preventing tryptophan depletion. Inhibition of IDO acutely in HIV infection inhibits viral replication, but chronic activation of IDO leads to immune impairment in AIDS. IDO is also the gatekeeper enzyme for kynurenine metabolism, a pathway involved in serotonin and melatonin biosynthesis and the regulation of glutamate and dopamine levels in the brain. Therefore inhibition of IDO might explain both the reported medicinal and neuropsychiatric effects of E. rheedei.