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2.
BMC Infect Dis ; 19(1): 848, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615436

RESUMO

BACKGROUND: Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. CASE PRESENTATION: A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient's left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. CONCLUSIONS: This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.


Assuntos
Doxorrubicina/análogos & derivados , Infecções por HIV/patologia , Sarcoma de Kaposi/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Coração/diagnóstico por imagem , Humanos , Masculino , Miocárdio/patologia , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/etiologia
3.
Rev Soc Bras Med Trop ; 52: e20180188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596345

RESUMO

Reports of simultaneous infections and neoplasms in patients with acquired immune deficiency syndrome (AIDS) are occasionally seen in the literature. However, coexistent lymphoma with tuberculosis, and Kaposi sarcoma (KS) with tuberculosis occurring in the same lymph node is rare. Coexistent lesions pose diagnostic difficulties. In this article, we report two HIV-positive patients from Zimbabwe who displayed KS and tuberculosis; KS and diffuse large B-cell lymphoma in the same lymph node. We found only one similar case presentation in the literature, which was reported in India.


Assuntos
Infecções por HIV/complicações , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/complicações , Sarcoma de Kaposi/complicações , Tuberculose/complicações , Adulto , Feminino , Infecções por HIV/patologia , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Sarcoma de Kaposi/patologia , Tuberculose/patologia , Zimbábue
4.
Toxicol Lett ; 317: 13-23, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31562912

RESUMO

Combination antiretroviral therapy (cART) has been hugely successful in reducing the mortality associated with human immunodeficiency virus (HIV) infection, resulting in a growing population of people living with HIV (PLWH). Since PLWH now have a longer life expectancy, chronic comorbidities have become the focus of the clinical management of HIV. For example, cardiovascular complications are now one of the most prevalent causes of death in PLWH. Numerous epidemiological studies show that antiretroviral treatment increases cardiovascular disease (CVD) risk and early onset of CVD in PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and two NRTIs are typically used in combination with one drug from another drug class, e.g., a fusion inhibitor. NRTIs are known to induce mitochondrial dysfunction, contributing to toxicity in numerous tissues, such as myopathy, lipoatrophy, neuropathy, and nephropathy. In in vitro studies, short-term NRTI treatment induces an endothelial dysfunction with an increased reactive oxygen species (ROS) production; long-term NRTI treatment decreases cell replication capacity, while increasing mtROS production and senescent cell accumulation. These findings suggest that a mitochondrial oxidative stress is involved in the pathogenesis of NRTI-induced endothelial dysfunction and premature senescence. Mitochondrial dysfunction, defined by a compromised mitochondrial quality control via biogenesis and mitophagy, has a causal role in premature endothelial senescence and can potentially initiate early cardiovascular disease (CVD) development in PLWH. In this review, we explore the hypothesis and present literature supporting that long-term NRTI treatment induces vascular dysfunction by interfering with endothelial mitochondrial homeostasis and provoking mitochondrial genomic instability, resulting in premature endothelial senescence.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Senescência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Animais , Fármacos Anti-HIV/administração & dosagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Esquema de Medicação , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Metabolismo Energético/efeitos dos fármacos , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
5.
BMC Infect Dis ; 19(1): 815, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533639

RESUMO

BACKGROUND: Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers. CASE PRESENTATION: In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, HIV specific antibody levels and CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells. CONCLUSION: This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1/genética , Humanos , RNA Viral/sangue , Carga Viral
6.
BMC Infect Dis ; 19(1): 821, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533734

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is common in men who have sex with men (MSM) with HIV. The Swiss HCVree Trial targeted a micro-elimination by using a treat and counsel strategy. Self-reported condomless anal intercourse with non-steady partners was used as the selection criterion for participation in a counselling intervention designed to prevent HCV re-infection. The purpose of this study was to assess the ability of this criterion to identify men who engaged in other sexual risk behaviours associated with HCV re-infection. METHODS: Men who disclosed their sexual and drug- use behaviours during the prior 6 months, at study baseline, were included in the current study. Using a descriptive comparative study design, we explored self-reported sexual and drug-use risk behaviours, compared the odds of reporting each behaviour in men who reported and denied condomless anal intercourse with non-steady partners during the prior year and calculated the sensitivity/specificity (95% CI) of the screening question in relation to the other at-risk behaviours. RESULTS: Seventy-two (61%) of the 118 men meeting eligibity criteria reported condomless anal intercourse with non-steady partners during the prior year. Many also engaged in other potential HCV transmission risk behaviours, e.g., 52 (44%) had used drugs. In participants disclosing drug use, 44 (37%) reported sexualised drug use and 17 (14%) injected drugs. Unadjusted odds ratios (95% CI) for two well-known risk behaviours were 2.02 (0.80, 5.62) for fisting and 5.66 (1.49, 37.12) for injecting drug use. The odds ratio for sexualised drug use - a potential mediator for increased sexual risk taking - was 5.90 (2.44, 16.05). Condomless anal intercourse with non-steady partners showed varying sensitivity in relation to the other risk behaviours examined (66.7-88.2%). CONCLUSIONS: Although condomless anal intercourse with non-steady partners was fairly sensitive in detecting other HCV relevant risk behaviours, using it as the only screening criterion could lead to missing a proportion of HIV-positive men at risk for HCV re-infection due to other behaviours. This work also points to the importance of providing access to behavioral interventions addressing other sexual and drug use practices as part of HCV treatment. TRIAL REGISTRATION: Clinical Trial Number: NCT02785666 , 30.05.2016.


Assuntos
Infecções por HIV/patologia , Hepatite C/diagnóstico , Adulto , Infecções por HIV/complicações , Hepatite C/complicações , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Assunção de Riscos , Autorrelato , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/patologia
7.
Life Sci ; 235: 116851, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31499070

RESUMO

AIMS: We performed a systematic review and meta-analysis on the effect of HIV infection and antiretroviral therapy (ART) on carotid intima-media thickness (cIMT) to elucidate the role of HIV infection and ART. Also, an analysis on the role of ethnicity and gender on cIMT in HIV-infected populations was performed. MAIN METHODS: We searched the PubMed, Web of Science, the WHO websites and International AIDS Society for published observational studies were conducted by two independent reviewers for studies comparing HIV-infected antiretroviral-experienced patients and/or inexperienced with healthy controls on cIMT. The primary outcome was the standardized mean difference (SMD) of cIMT. FINDINGS: Twenty studies (five cohort, 15 cross-sectional, and two both cohort and cross-sectional studies) were identified comprising 7948 subjects (4656 HIV-infected; 3292 controls). In cohort studies, the standardized mean 1-year change in cIMT between HIV-infected patients and uninfected controls was not significantly different (0.16 mm/yr; 95% CI, -0.16, 0.49; p = 0.326). In 17 cross-sectional studies, the SMD in cIMT was significantly higher in HIV-infected than uninfected persons (0.27 mm; 95% CI, 0.04, 0.49; p = 0.027). HIV-infected patients on ART exhibited significantly higher SMD in cIMT compared to those not on ART (0.75 mm; 95% CI, 0.30, 1.19; p = 0.001). No confounding effect of gender and ethnicity could be established using meta-regression p > 0.05. SIGNIFICANCE: HIV infection itself and ART appear to influence the progression of cIMT and hence may be risk factors for cardiovascular events. No firm conclusions could be drawn on the effect of ethnic/race and gender differences on cIMT in HIV-infected populations.


Assuntos
Antirretrovirais/efeitos adversos , Espessura Intima-Media Carotídea , Infecções por HIV/dietoterapia , Infecções por HIV/patologia , Grupos Étnicos , Humanos , Caracteres Sexuais
8.
Nutrients ; 11(8)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370174

RESUMO

Women aging with human immunodeficiency virus (HIV) are particularly vulnerable to cognitive decline. Recent studies have highlighted the potential protective effects of olive oil on cognition in persons living without HIV. We sought to evaluate the association between olive oil consumption and domain-specific cognitive performance (dCog) t-scores (adjusted for age, race, education, reading level, practice effects) in women living with HIV (WLWH) and sociodemographically similar women living without HIV. A total of 166 women (113 WLWH and 53 women living without HIV) participating in the Cook County Women's Interagency HIV Study (WIHS) completed cognitive testing and a Block 2014 Food Frequency Questionnaire within 18 months. Use of olive oil was associated with a 4.2 point higher attention/concentration (p = 0.02), 4.0 point higher for verbal learning (p = 0.02), and 1.91 point higher for verbal memory (p = 0.05). Associations between using olive oil and attention/concentration cognitive domain were seen in WLWH but not in women living without HIV. Associations between olive oil and verbal learning and memory were only seen in women without HIV. Our data suggest that using olive oil as a primary cooking oil may contribute to differential effects in attention/concentration, verbal learning, and verbal memory between women living with and without HIV.


Assuntos
Atenção/efeitos dos fármacos , Infecções por HIV/patologia , Azeite de Oliva , Adulto , Estudos de Casos e Controles , Chicago/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade
10.
Surg Pathol Clin ; 12(3): 771-782, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352987

RESUMO

HIV infection is associated with an increased risk for developing B-cell lymphoproliferative disorders. The spectrum of disease differs in HIV-infected versus HIV-uninfected persons, with aggressive B-cell non-Hodgkin lymphomas constituting a higher proportion of all lymphoproliferative disorders in the HIV-positive population. Although antiretroviral therapy (ART) has significantly changed the landscape of lymphomas arising in HIV-infected persons, population growth and aging are reflected in the steady increase in non-AIDS-defining cancers. In the ART era, outcomes for HIV-infected lymphoma patients are similar to those of HIV-negative patients. This article reviews the diagnostic features and summarizes current biologic understanding of HIV-associated lymphomas.


Assuntos
Infecções por HIV/patologia , Linfoma de Células B/virologia , Fármacos Anti-HIV/uso terapêutico , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Diagnóstico Diferencial , Infecções por HIV/tratamento farmacológico , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma de Células B/patologia , Linfoma de Efusão Primária/patologia , Linfoma de Efusão Primária/virologia , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/virologia
11.
BMC Res Notes ; 12(1): 452, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337435

RESUMO

OBJECTIVE: This was a 5 year retrospective study of patients' hospital records to find out how patients with cellulitis are managed and the care provided by nurses to these patients in some hospitals in Fako, Cameroon. RESULTS: Of the 236 cases of cellulitis identified from a study of hospital records, 202 were included in the study. Most of the participants (55%) were female and the mean (SD) age was 43 (1.1) years. Cellulitis accounted for 2.3% of admissions in this study. The predisposing factors identified were; the presence of trauma (60.5%), HIV infection (18.6%), alcohol consumption (8.4%) and tobacco use (4.8%). Commonly recorded complications were necrosis (32.2%), sepsis (23%), abscess formation (19.5%), and ulcer development (19.5%). Medical management was with antibiotic therapy, including mostly penicillin (26.5%), aminoglycoside (22.1%), nitroimidazole (20.2%) and cephalosporin (19.6%). Debridement (46.7%), and incision and drainage (44.4%) were the most implemented surgical interventions. Nursing care, as found in patients' hospital records were predominantly on medication administration (98.0%), vital signs assessment (90.5%) and patient assessment (53%). Cellulitis therefore was found among a substantial number of patients and management was predominantly with combination antibiotics therapy and inadequate nursing care.


Assuntos
Antibacterianos/uso terapêutico , Celulite (Flegmão)/terapia , Desbridamento/métodos , Drenagem/métodos , Papel do Profissional de Enfermagem/psicologia , Abscesso/diagnóstico , Abscesso/patologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/fisiopatologia , Aminoglicosídeos/uso terapêutico , Camarões , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/cirurgia , Cefalosporinas/uso terapêutico , Gerenciamento Clínico , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/patologia , Nitroimidazóis/uso terapêutico , Enfermeiras e Enfermeiros/organização & administração , Penicilinas/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Fatores de Risco , Sepse/diagnóstico , Sepse/patologia , Fumar/efeitos adversos , Fumar/fisiopatologia , Úlcera/diagnóstico , Úlcera/patologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/patologia
12.
Biomed Res Int ; 2019: 4523475, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346517

RESUMO

Background: Young people in Sub-Saharan Africa are affected by HIV pandemic to a greater extent than elsewhere. Transactional sex among adolescent school girls with older men commonly called "sugar daddies" is one of the major factors fueling the spread of the infection due to the extended sexual network. Thus, this study aimed to assess the magnitude and factors associated with transactional sex among adolescent girls and "sugar daddies" in relation to HIV/AIDS. Methods: Mixed method cross-sectional study was done among 620 female students in Hawassa town, South Ethiopia, from September 2010 to May 2011. A structured questionnaire and in-depth interview check list were used to collect the quantitative and qualitative data, respectively. Survey participants were selected randomly from five preparatory schools whereas ten in-depth interview participants were recruited by a snowball sampling technique from the same schools. Data were entered using Epi-Info and analyzed by SPSS. A descriptive statistics followed by multivariable logistic regression analyses were conducted to identify factors associated with transactional sex with "sugar daddy". Both crude and adjusted odds ratios with 95% confidence interval were reported. We used OpenCode software for coding and categorizing the in-depth interviews and quotes that represent the informants opinion were used to support the quantitative findings. Results: A substantial number of female students, 71(11.5%), reported to have had transactional sex with older men. Most of the respondents who dated "sugar daddies" (93%) had multiple sexual partners concurrently and sequentially, and among them, only 22.7% had consistent condom use. Girls who were in older age group [OR (CI) 6.87 (3.48-13.58)], who had lost both parents [OR (CI) 2.99 (1.14-7.84)], had perceived less economic status [OR: 25.41; 95% CI: 7.80-82.76] and engaged in substance abuse [OR (CO) 5.8 (2.1-15.77)] had higher odds of practicing transactional sex with "sugar daddies". In-depth interviewed participants also revealed that they were involved in transactional sex for monetary while having concurrent and subsequent sexual network with their schoolmates and other young partners. Conclusion: Transactional sex among female students was high, and the sexual network they had with the young men put young people in the network at risk of HIV and other sexually transmitted infections. Therefore, HIV prevention programs shall focus on transactional sex among adolescent school girls to halt transmission of HIV among the generation.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Doenças Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Etiópia/epidemiologia , Feminino , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Assunção de Riscos , Instituições Acadêmicas , Parceiros Sexuais/psicologia , Doenças Sexualmente Transmissíveis/patologia , Doenças Sexualmente Transmissíveis/virologia , Fatores Socioeconômicos , Estudantes/psicologia , Inquéritos e Questionários , Adulto Jovem
13.
PLoS Pathog ; 15(7): e1007869, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31291371

RESUMO

Clonal expansion of HIV infected cells plays an important role in the formation and persistence of the reservoir that allows the virus to persist, in DNA form, despite effective antiretroviral therapy. We used integration site analysis to ask if there is a similar clonal expansion of SIV infected cells in macaques. We show that the distribution of HIV and SIV integration sites in vitro is similar and that both viruses preferentially integrate in many of the same genes. We obtained approximately 8000 integration sites from blood samples taken from SIV-infected macaques prior to the initiation of ART, and from blood, spleen, and lymph node samples taken at necropsy. Seven clones were identified in the pre-ART samples; one persisted for a year on ART. An additional 100 clones were found only in on-ART samples; a number of these clones were found in more than one tissue. The timing and extent of clonal expansion of SIV-infected cells in macaques and HIV-infected cells in humans is quite similar. This suggests that SIV-infected macaques represent a useful model of the clonal expansion of HIV infected cells in humans that can be used to evaluate strategies intended to control or eradicate the viral reservoir.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Animais , Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/virologia , Reservatórios de Doenças/virologia , Infecções por HIV/patologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Técnicas In Vitro , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Vírus da Imunodeficiência Símia/patogenicidade , Carga Viral/efeitos dos fármacos , Integração Viral/genética , Integração Viral/fisiologia , Replicação Viral/efeitos dos fármacos
14.
BMC Infect Dis ; 19(1): 599, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288748

RESUMO

BACKGROUND: Second-line Antiretroviral Therapy (ART) regimens are used when patients develop treatment failure for first-line drug regimens. It is costly unaffordable and it is not widely available for patients in resource limiting setting, there is a need to maximizing the duration of stay on second-line regimen. This study was conducted to estimate the incidence rate of second-line treatment failure and to identify its predictors among adults living with HIV in the Amhara region. METHODS: An institution based retrospective follow-up study was conducted from May to June 2017. A total of 1,011 adults on second-line ART who were enrolled between February 2008 and April 2016 were included for final analysis. Kaplan-Meier estimator curves were used to describe the survival function. Semi-parametric proportional hazard model was fitted to identify the predictors of treatment failure. RESULTS: The overall incidence of second-line treatment failure was 9.86 per 100 person-years. It was high during the first and the last year of follow-up. The rate of second-line treatment failure was higher for patients who didn't change second-line regimens (HR: 1.55, 95%CI: 1.18-2.04), who had poor ART adherence (HR: 1.40, 95%CI: 1.06-1.85), and not taking INH (HR: 1.68, 95%CI: 1.23-2.30) as compared to their counter group. The rate of treatment failure for patients who were under WHO clinical stage III at switch (HR: 0.68, 95%CI: 0.50-0.91) was also lower as compared to clients who were under WHO clinical stage I. Furthermore, the rate of treatment failure was higher for clients who were under second-line regimen "TDF-3TC-LPV/r" (HR: 1.55, 95%CI: 1.03-2.32) and "AZT-3TC-LPV/r" (HR: 3.00, 95%CI: 1.86-4.85) as compared to patients under "ABC-ddI-LPV/r" regimens. CONCLUSIONS: A high incidence rate of second-line treatment failure was noticed in the study setting. The rate of second-line treatment failure was higher for patients who didn't change drug regimens, who had poor ART adherence, and who were not taking INH. Therefore, addressing significant predictors to prevent treatment failure among ART patients is essential and sustainable monitoring to reduce the risk of treatment failure is also desirable.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Falha de Tratamento , Adulto Jovem
15.
Nutrients ; 11(6)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181624

RESUMO

BACKGROUND: People living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) (PLWH) are at an increased risk of cardiovascular disease. Diet-related factors may contribute. The aim of this pilot study was to determine, in PLWH, the relationship between atherosclerosis assessed by carotid intima-media thickness (CIMT) and (A) plasma antioxidant micronutrients and oxidative stress or (B) red blood cell polyunsaturated fatty acids (RBC PUFA), particularly long chain omega-3 polyunsaturated fatty acids (n-3 PUFA). METHODS: (A) In a cross-sectional study, subjects had CIMT evaluated by high resolution carotid artery ultrasound. Plasma was collected for vitamin C, measured by spectrophotometry; and alpha- and gamma-tocopherol, retinol, and malondialdehyde-a marker of oxidative stress-using high pressure liquid chromatography and fluorescence spectrophotometry. (B) In a prospective cohort study, other subjects had RBC PUFA measured at baseline, using gas chromatography, and CIMT assessed at baseline and repeated after 2 years. Clinical data was also collected. RESULTS: (A) 91 PLWH participated. Only alpha- and gamma-tocopherol levels were positively correlated with CIMT. In a multivariate analysis, age and systolic blood pressure were significantly associated with CIMT with gamma-tocopherol near significance (p = 0.053). (B) 69 PLWH participated. At baseline, docosahexaenoic acid (n-3 PUFA) and the ratio of docosahexaenoic acid to arachidonic acid (n-6 PUFA) were significantly and negatively correlated with CIMT. However, a multivariate analysis failed to detect a significant relationship either at baseline or 2 years after. CONCLUSION: In addition to age and systolic blood pressure, atherosclerosis assessed by CIMT might be associated with higher serum gamma-tocopherol levels. There was a non-significant association between CIMT and RBC n-3 PUFA or the ratio of n-3 to n-6 PUFA.


Assuntos
Antioxidantes/metabolismo , Aterosclerose/etiologia , Eritrócitos/metabolismo , Ácidos Graxos Insaturados/sangue , Infecções por HIV/complicações , Estresse Oxidativo , gama-Tocoferol/sangue , Adulto , Ácido Araquidônico/sangue , Aterosclerose/sangue , Aterosclerose/patologia , Pressão Sanguínea , Espessura Intima-Media Carotídea , Estudos Transversais , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/patologia , Humanos , Masculino , Malondialdeído/sangue , Micronutrientes/sangue , Pessoa de Meia-Idade , Análise Multivariada , Projetos Piloto , Estudos Prospectivos , alfa-Tocoferol/sangue
16.
Cell Host Microbe ; 26(1): 86-99.e7, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31253590

RESUMO

The Cullin-RING E3 ligase (CRL) family is commonly hijacked by pathogens to redirect the host ubiquitin proteasome machinery to specific targets. During HIV infection, CRL5 is hijacked by HIV Vif to target viral restriction factors of the APOBEC3 family for ubiquitination and degradation. Here, using a quantitative proteomics approach, we identify the E3 ligase ARIH2 as a regulator of CRL5-mediated APOBEC3 degradation. The CUL5Vif/CBFß complex recruits ARIH2 where it acts to transfer ubiquitin directly to the APOBEC3 targets. ARIH2 is essential for CRL5-dependent HIV infectivity in primary CD4+ T cells. Furthermore, we show that ARIH2 cooperates with CRL5 to prime other cellular substrates for polyubiquitination, suggesting this may represent a general mechanism beyond HIV infection and APOBEC3 degradation. Taken together, these data identify ARIH2 as a co-factor in the Vif-hijacked CRL5 complex that contributes to HIV infectivity and demonstrate the operation of the E1-E2-E3/E3-substrate ubiquitination mechanism in a viral infection context.


Assuntos
Desaminase APOBEC-3G/metabolismo , Proteínas Culina/metabolismo , Infecções por HIV/patologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Ubiquitina-Proteína Ligases/metabolismo , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Humanos , Modelos Teóricos , Proteólise , Proteoma/análise , Replicação Viral
18.
Expert Opin Pharmacother ; 20(14): 1719-1729, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31232617

RESUMO

Introduction: Cardiovascular disease is an important cause of morbidity and mortality in persons with human immunodeficiency virus (PWH). The risk of atherosclerotic cardiovascular disease (ASCVD) is higher in PWH compared to uninfected persons. Dyslipidemia is a critical link in the pathogenesis of ASCVD in PWH. Chronic inflammation associated with HIV infection may drive both dyslipidemia and ASCVD. Areas covered: The authors review the evidence for using lipid-lowering therapy in PWH and includes an overview of the utility and complexity of using statins in PWH, in particular, drug interactions, safety, and efficacy. In addition, data covering alternate therapies like omega-3 fatty acids, fibrates, niacin, ezetimibe, and PCSK-9 inhibitors are reviewed. Expert opinion: Dyslipidemia is a common problem in PWH. The risk of ASCVD is higher in PWH. Lipid-lowering therapy reduces the risk of ASCVD, but clinical endpoint trials are lacking in PWH. Statin therapy is the mainstay of primary prevention for ASCVD. The timing of when to initiate primary prevention with statins in PWH is unclear. Beyond statins, there are limited data that other lipid-lowering agents have utility in PWH. Ongoing trials like the REPRIEVE trial will inform the community about the optimal approach to lipid-lowering therapy in PWH.


Assuntos
Dislipidemias/tratamento farmacológico , Infecções por HIV/patologia , Hipolipemiantes/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/química , Antirretrovirais/uso terapêutico , Interações de Medicamentos , Dislipidemias/etiologia , Ezetimiba/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Medição de Risco
19.
PLoS Pathog ; 15(6): e1007868, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31220191

RESUMO

We previously reported the presence of memory CD4+ T cells that express low levels of SAMHD1 (SAMHD1low) in peripheral blood and lymph nodes from both HIV-1 infected and uninfected individuals. These cells are enriched in Th17 and Tfh subsets, two populations known to be preferentially targeted by HIV-1. Here we investigated whether SAMHD1low CD4+ T-cells harbour replication-competent virus and compartimentalized HIV-1 genomes. We sorted memory CD4+CD45RO+SAMHD1low, CD4+CD45RO+SAMHD1+ and naive CD4+CD45RO-SAMHD1+ cells from HIV-1-infected patients on anti-retroviral therapy (c-ART) and performed HIV-1 DNA quantification, ultra-deep-sequencing of partial env (C2/V3) sequences and phenotypic characterization of the cells. We show that SAMHD1low cells include novel Th17 CCR6+ subsets that lack CXCR3 and CCR4 (CCR6+DN). There is a decrease of the % of Th17 in SAMHD1low compartment in infected compared to uninfected individuals (41% vs 55%, p<0.05), whereas the % of CCR6+DN increases (7.95% vs 3.8%, p<0.05). Moreover, in HIV-1 infected patients, memory SAMHD1low cells harbour high levels of HIV-1 DNA compared to memory SAMHD1+ cells (4.5 vs 3.8 log/106cells, respectively, p<0.001), while naïve SAMHD1+ showed significantly lower levels (3.1 log/106cells, p<0.0001). Importantly, we show that SAMHD1low cells contain p24-producing cells. Moreover, phylogenetic analyses revealed well-segregated HIV-1 DNA populations with compartmentalization between SAMHD1low and SAMHD1+ memory cells, and limited viral exchange. As expected, the % of Ki67+ cells was significantly higher in SAMHD1low compared to SAMHD1+ cells. There was positive association between levels of HIV-1 DNA and Ki67+ in memory SAMHD1low cells, but not in memory and naïve SAMHD1+ CD4+ T-cells. Altogether, these data suggest that proliferative memory SAMHD1low cells contribute to viral persistence.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Memória Imunológica , Proteína 1 com Domínio SAM e Domínio HD/imunologia , Adulto , Idoso , Antirretrovirais/administração & dosagem , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade
20.
BMC Infect Dis ; 19(1): 544, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221100

RESUMO

BACKGROUND: Bedaquiline was recently introduced into World Health Organization (WHO)-recommended regimens for treatment of drug resistant tuberculosis. There is limited data on the long-term safety of bedaquiline. Because bedaquiline prolongs the QT interval, there are concerns regarding cardiovascular safety. The Western Cape Province in South Africa has an established pharmacovigilance programme: a targeted spontaneous reporting system which solicits reports of suspected adverse drug reactions (ADRs) in patients with HIV-1 and/or tuberculosis infection. Since 2015, bedaquiline has been included in the treatment regimens recommended for resistant tuberculosis in South Africa. We describe ADRs in patients on bedaquiline-containing tuberculosis treatment that were reported to the Western Cape Pharmacovigilance programme. METHODS: We reviewed reports of suspected ADRs and deaths received between March 2015 and June 2016 involving patients receiving bedaquiline-containing tuberculosis treatment. A multidisciplinary panel assessed causality, and categorised suspected ADRs using World Health Organisation-Uppsala Monitoring Centre system categories. "Confirmed ADRs" included all ADRs categorised as definite, probable or possible. Preventability was assessed using Schumock and Thornton criteria. Where a confirmed ADR occurred in a patient who died, the panel categorised the extent to which the ADR contributed to the patient's death as follows: major contributor, contributor or non-contributor. RESULTS: Thirty-five suspected ADRs were reported in 32 patients, including 13 deaths. There were 30 confirmed ADRs, of which 23 were classified as "possible" and seven as "probable". Bedaquiline was implicated in 22 confirmed ADRs in 22 patients. The most common confirmed ADR in patients receiving bedaquiline was QT prolongation (8 cases, 7 of which were severe). A fatal arrhythmia was suspected in 4 sudden deaths. These 4 patients were all taking bedaquiline together with other QT-prolonging drugs. There were 8 non-bedaquiline-associated ADRs, of which 7 contributed to deaths. CONCLUSIONS: Confirmed ADRs in patients receiving bedaquiline reflect the known safety profile of bedaquiline. Quantifying the incidence and clinical consequences of severe QT-prolongation in patients receiving bedaquiline-containing regimens is a research priority to inform recommendations for patient monitoring in treatment programmes for drug resistant tuberculosis. Pharmacovigilance systems within tuberculosis treatment programmes should be supported and encouraged, to provide ongoing monitoring of treatment-limiting drug toxicity.


Assuntos
Antituberculosos/efeitos adversos , Doenças Cardiovasculares/etiologia , Diarilquinolinas/efeitos adversos , Adulto , Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/etiologia , Masculino , África do Sul , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/patologia , Adulto Jovem
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