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3.
Blood ; 136(11): 1284-1297, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32430507

RESUMO

EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Genes myc , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Contagem de Linfócito CD4 , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , DNA Viral/sangue , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/isolamento & purificação , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Linfoma Relacionado a AIDS/complicações , Linfoma Relacionado a AIDS/genética , Linfoma Relacionado a AIDS/virologia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Carga Viral/efeitos dos fármacos , Vorinostat/administração & dosagem , Vorinostat/efeitos adversos
4.
Artigo em Inglês | MEDLINE | ID: mdl-32294049

RESUMO

HIV-positive patients have a 60- to 200-fold increased incidence of Non-Hodgkin Lymphomas (NHL) because of their impaired cellular immunity. Some NHL are considered Acquired Immunodeficiency Syndrome (AIDS) defining conditions. Diffuse large B-cell Lymphoma (DLBC) and Burkitt Lymphoma (BL) are the most commonly observed, whereas Primary Effusion Lymphoma (PEL), Central Nervous System Lymphomas (PCNSL), Plasmablastic Lymphoma (PBL) and classic Hodgkin Lymphoma (HL) are far less frequent. Multicentric Castleman disease (MCD) is an aggressive lymphoproliferative disorder highly prevalent in HIV-positive patients and strongly associated with HHV-8 virus infection. In the pre-Combination Antiretroviral Therapy (CART) era, patients with HIV-associated lymphoma had poor outcomes with median survival of 5 to 6 months. By improving the immunological status, CART extended the therapeutic options for HIV positive patients with lymphomas, allowing them to tolerate standard chemotherapies regimen with similar outcomes to those of the general population. The combination of CART and chemotherapy/ immuno-chemotherapy treatment has resulted in a remarkable prolongation of survival among HIVinfected patients with lymphomas. In this short communication, we briefly review the problems linked with the treatment of lymphoproliferative diseases in HIV patients. Combination Antiretroviral Therapy (CART) not only reduces HIV replication and restores the immunological status improving immune function of the HIV-related lymphomas patients but allows patients to deal with standard doses of chemotherapies. The association of CART and chemotherapy allowed to obtain better results in terms of overall survival and complete responses. In the setting of HIVassociated lymphomas, many issues remain open and their treatment is complicated by the patient's immunocompromised status and the need to treat HIV concurrently.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Animais , Terapia Antirretroviral de Alta Atividade , HIV/efeitos dos fármacos , HIV/imunologia , HIV/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/etiologia , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Replicação Viral/efeitos dos fármacos
5.
Cancer Med ; 9(2): 552-561, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31782984

RESUMO

Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P = .048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P = .014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA.


Assuntos
Biomarcadores Tumorais/sangue , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por HIV/complicações , Herpesvirus Humano 4/genética , Linfoma Relacionado a AIDS/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Idoso , DNA Viral/genética , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , HIV/isolamento & purificação , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfoma Relacionado a AIDS/sangue , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/virologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/virologia , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
6.
Blood ; 134(17): 1385-1394, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30992269

RESUMO

Cancer is the leading cause of death for HIV-infected persons in economically developed countries, even in the era of antiretroviral therapy (ART). Lymphomas remain a leading cause of cancer morbidity and mortality for HIV-infected patients and have increased incidence even in patients optimally treated with ART. Even limited interruptions of ART can lead to CD4 cell nadirs and HIV viremia, and increase the risk of lymphoma. The treatment of lymphoma is now similar for HIV-infected patients and the general population: patients with good HIV control can withstand intensive therapies appropriate to the lymphoma, including autologous and even allogeneic hematopoietic stem cell transplantation. Nonetheless, HIV-related lymphomas have unique aspects, including differences in lymphoma pathogenesis, driven by the presence of HIV, in addition to coinfection with oncogenic viruses. These differences might be exploited in the future to inform therapies. The relative incidences of lymphoma subtypes also differ in the HIV-infected population, and the propensity to advanced stage, aggressive presentation, and extranodal disease is higher. Other unique aspects include the need to avoid potential interactions between ART and chemotherapeutic agents, and the need for HIV-specific supportive care, such as infection prophylaxis. Despite these specific challenges for cancer treatment in the setting of HIV infection, the care of these patients has progressed sufficiently that recent guidelines from the American Society of Clinical Oncology advocate the inclusion of HIV-infected patients alongside HIV- patients in cancer clinical trials when appropriate.


Assuntos
Linfoma Relacionado a AIDS/terapia , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Terapia Genética/métodos , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/métodos , Linfoma Relacionado a AIDS/virologia
7.
Cancer Treat Res ; 177: 81-103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30523622

RESUMO

Herpesvirus-induced disease is one of the most lethal factors which leads to high mortality in HIV/AIDS patients. EBV, also known as human herpesvirus 4, can transform naive B cells into immortalized cells in vitro through the regulation of cell cycle, cell proliferation, and apoptosis. EBV infection is associated with several lymphoma and epithelial cancers in humans, which occurs at a much higher rate in immune deficient individuals than in healthy people, demonstrating that the immune system plays a vital role in inhibiting EBV activities. EBV latency infection proteins can mimic suppression cytokines or upregulate PD-1 on B cells to repress the cytotoxic T cells response. Many malignancies, including Hodgkin Lymphoma and non-Hodgkin's lymphomas occur at a much higher frequency in EBV positive individuals than in EBV negative people during the development of HIV infection. Importantly, understanding EBV pathogenesis at the molecular level will aid the development of novel therapies for EBV-induced diseases in HIV/AIDS patients.


Assuntos
Síndrome de Imunodeficiência Adquirida , Herpesvirus Humano 4 , Neoplasias , Síndrome de Imunodeficiência Adquirida/fisiopatologia , Síndrome de Imunodeficiência Adquirida/virologia , Carcinogênese , Coinfecção/virologia , Infecções por Vírus Epstein-Barr/fisiopatologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Herpesvirus Humano 4/fisiologia , Humanos , Hospedeiro Imunocomprometido , Linfoma Relacionado a AIDS/fisiopatologia , Linfoma Relacionado a AIDS/virologia , Neoplasias/fisiopatologia , Neoplasias/virologia
8.
Clin Infect Dis ; 68(5): 834-843, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29982484

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in human immunodeficiency virus (HIV)-infected patients. Our aim was to evaluate the usefulness of plasma EBV load as biomarker and prognostic factor in HIV-positive patients with lymphomas. METHODS: EBV loads were measured by polymerase chain reaction in plasma samples of 81 HIV-positive patients' lymphomas at different moments: within 1 year before lymphoma diagnosis, at diagnosis, and at complete response (CR). Control samples included HIV-negative patients with lymphomas and HIV-positive patients without neoplasia or opportunistic infections. RESULTS: HIV-positive patients with lymphomas had more frequently-detectable EBV load at lymphoma diagnosis (53%) than either HIV-negative patients with the same lymphoma type (16%; P < .001) or HIV-positive individuals without neoplasia or opportunistic infection (1.2%; P < .001). HIV-positive lymphoma patients with detectable EBV load in plasma at lymphoma diagnosis had statistically significant decrease of EBV load at CR. High EBV load (>5000 copies/mL) at lymphoma diagnosis was an independent negative prognostic factor for overall survival and progression-free survival in HIV-positive patients with lymphomas. Detectable plasma EBV loads identified HIV-positive subjects that would eventually develop lymphoma (area under the curve, 82%; 95% CI: 0.67-0.96). CONCLUSIONS: Plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-positive patients with lymphomas. The presence of the EBV load in the plasma of an HIV-positive patient can be an early predictor of lymphoma development.


Assuntos
Infecções por HIV/complicações , Herpesvirus Humano 4 , Linfoma Relacionado a AIDS/virologia , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Infecções por HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
9.
Infect Dis (Lond) ; 50(11-12): 847-852, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30317893

RESUMO

INTRODUCTION: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma. METHODS: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls). RESULTS: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis. CONCLUSIONS: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Infecções por HIV/complicações , Herpesvirus Humano 4/isolamento & purificação , Linfoma Relacionado a AIDS/diagnóstico , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Infecções por Vírus Epstein-Barr/complicações , Feminino , Infecções por HIV/virologia , Herpesvirus Humano 4/genética , Humanos , Estudos Longitudinais , Linfoma Relacionado a AIDS/complicações , Linfoma Relacionado a AIDS/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Risco , Carga Viral
10.
J Glob Oncol ; 4: 1-11, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241264

RESUMO

PURPOSE: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)-an AIDS-defining cancer-in the country. PATIENTS AND METHODS: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. RESULTS: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001). CONCLUSION: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Botsuana/epidemiologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/virologia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Prospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Estados Unidos/epidemiologia , Vincristina/uso terapêutico
11.
Clin Lymphoma Myeloma Leuk ; 18(8): 548-551, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29937399

RESUMO

BACKGROUND: HIV-associated lymphomas (HAL) remain an important cause of morbidity and mortality in HIV patients, especially in the setting of treatment-refractory disease. Hematopoietic cell transplantation (HCT) is considered a curative option for patients with refractory HAL. PATIENTS AND METHODS: We report the efficacy of autologous HCT in 20 patients with HAL [non-Hodgkin lymphoma = 14 (70%), Hodgkin lymphoma = 6 (30%)]. At the time of transplantation, the median peripheral blood CD4+ count was 226 cells/µL. HIV virus load was undetectable in 14 (70%) of 20 patients. RESULTS: The median follow-up of surviving patients was 47 months (range, 20-119 months). The median time to neutrophil engraftment was 11 days. The median progression-free survival and median overall survival have not been reached. At 4 years after transplantation, progression-free survival and overall survival were 65% and 70%, respectively. Six patients died from disease relapse or progression (n = 5) and infection (n = 1). Nonrelapse mortality was 0 and 5% at 100 days and 4 years after transplantation, respectively. CONCLUSION: Autologous HCT is an effective therapy for refractory/relapsed HAL with manageable toxicity, similar to non-HIV patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Linfoma Relacionado a AIDS/terapia , Linfoma não Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Progressão da Doença , Estudos de Viabilidade , Feminino , Florida , HIV/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/virologia , Humanos , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/mortalidade , Linfoma Relacionado a AIDS/virologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Carga Viral
12.
Int J Cancer ; 143(6): 1348-1355, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29663358

RESUMO

The aim of this study was to assess the association between HIV infection and cancer risk in Rwanda approximately a decade after the introduction of antiretroviral therapy (cART). All persons seeking cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda from 2012 to 2016 were routinely screened for HIV, prior to being confirmed with or without cancer (cases and controls, respectively). Cases were coded according to ICD-O-3 and converted to ICD10. Associations between individual cancer types and HIV were estimated using adjusted unconditional logistic regression. 2,656 cases and 1,196 controls differed by gender (80.3% vs. 70.8% female), age (mean 45.5 vs. 37.7 years), place of residence and proportion of diagnoses made by histopathology (87.5% vs. 67.4%). After adjustment for these variables, HIV was significantly associated with Kaposi Sarcoma (n = 60; OR = 110.3, 95%CI 46.8-259.6), non-Hodgkin lymphoma (NHL) (n = 265; OR = 2.5, 1.4-4.6), Hodgkin lymphoma (HL) (n = 76; OR = 5.2, 2.3-11.6) and cancers of the cervix (n = 560; OR = 5.9, 3.8-9.2), vulva (n = 23; OR = 17.8, 6.3-50.1), penis (n = 29; OR = 8.3, 2.5-27.4) and eye (n = 17; OR = 4.7, 1.0-25.0). Associations varied by NHL/HL subtype, with that for NHL being limited to DLBCL (n = 56; OR = 6.6, 3.1-14.1), particularly plasmablastic lymphoma (n = 6, OR = 106, 12.1-921). No significant associations were seen with other commonly diagnosed cancers, including female breast cancer (n = 559), head and neck (n = 116) and colorectal cancer (n = 106). In conclusion, in the era of cART in Rwanda, HIV is associated with increased risk of a range of infection-related cancers, and accounts for an important fraction of cancers presenting to a referral hospital.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , HIV/isolamento & purificação , Doença de Hodgkin/epidemiologia , Linfoma Relacionado a AIDS/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Doença de Hodgkin/virologia , Humanos , Incidência , Linfoma Relacionado a AIDS/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Ruanda/epidemiologia , Taxa de Sobrevida , Adulto Jovem
13.
Eur J Haematol ; 101(1): 119-126, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29663523

RESUMO

The introduction of combination antiretroviral therapy (cART) drastically improved performance status, immune function, and life expectancy of HIV-infected individuals. In addition, incidence of opportunistic infections and of AIDS-defining malignancies declined. Nevertheless, aggressive non-Hodgkin's lymphoma still remains the leading cause of AIDS-related deaths. The availability of cART, however, significantly improved the therapeutic options for HIV-positive patients with lymphomas. Diffuse large B-cell lymphoma, Burkitt's lymphoma, or Hodgkin lymphoma has increasingly become curable diseases. In light of these favorable developments in the treatment of HIV and HIV-associated lymphomas, reduction in treatment-associated toxicities and further improvement of outcome of patients with advanced immune suppression are major requirements for future clinical trials. This review summarizes the current treatment landscape and gives an overview on future needs in HIV-positive patients with lymphoma.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Doença de Hodgkin/tratamento farmacológico , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Antineoplásicos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/virologia , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Infecções por HIV/diagnóstico , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/virologia , Humanos , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/mortalidade , Linfoma Relacionado a AIDS/virologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/virologia , Análise de Sobrevida , Resultado do Tratamento
14.
Med Oncol ; 35(4): 53, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29536181

RESUMO

In HIV-seronegative patients with advanced Hodgkin lymphoma (HL), Epstein-Barr virus (EBV) viraemia at diagnosis predicts a worse progression-free survival (PFS), independent of the International Prognostic Score. However, its role in HIV-associated HL is uncharacterised. We collected clinico-pathologic and treatment data from a prospective series of 44 HIV-associated HLs from 2000 to 2016. We evaluated circulating EBV DNA as a prognostic factor on uni- and multivariable analyses in relationship to the International Prognostic Index criteria. In 44 patients with HIV-associated HL, EBV was detected by in situ hybridisation in all diagnostic biopsies. Blood EBV DNA was detectable in 26 patients (59%) with a median of 600 copies/mL (range 0-161,000). EBV DNA was independent of CD4 cell count (p = 0.9) or HIV viral load (p = 0.6) and did not predict PFS (HR 1.6, 95% CI 0.39-6.7, p = 0.49). EBV DNA is not a prognostic trait in HIV-associated HL. Prognostication in HIV-associated HL should be solely based on the International Prognostic Index criteria.


Assuntos
DNA Viral/sangue , Infecções por HIV/virologia , Herpesvirus Humano 4/genética , Doença de Hodgkin/virologia , Linfoma Relacionado a AIDS/virologia , DNA Viral/genética , Feminino , Infecções por HIV/sangue , Doença de Hodgkin/sangue , Humanos , Hibridização In Situ , Linfoma Relacionado a AIDS/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Carga Viral
15.
Rev. chil. infectol ; 34(5): 507-510, oct. 2017. graf
Artigo em Espanhol | LILACS | ID: biblio-899751

RESUMO

Resumen Las manifestaciones clínicas en los niños con infección por el virus de la inmunodeficiencia humana (VIH) de transmisión perinatal, pueden ser de inicio precoz o tardío. El linfoma asociado a VIH es una manifestación tardía que se asocia a estadios avanzados de inmunosupresión. Se presenta el caso de un escolar de 9 años con diagnóstico de novo de infección por VIH que debutó con un linfoma de Burkitt. En niños, la frecuencia de esta asociación es de 1-2% con pocos casos reportados en la literatura médica.


Children with perinatal human immunodeficiency virus (HIV) infection can present early or late clinical disease. HIV-associated lymphoma is a later manifestation that is associated with advanced immunosuppression (acquired immunodeficiency syndrome -AIDS). This is a case of a 9-year-old boy with recent diagnosis of HIV with Burkitt's lymphoma as first clinical manifestation. In children, the frequency of this association is very low and there are few cases reported.


Assuntos
Humanos , Masculino , Criança , Linfoma de Burkitt/virologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/congênito , Linfoma Relacionado a AIDS/virologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Resultado do Tratamento , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas , Progressão da Doença , Terapia Antirretroviral de Alta Atividade
18.
J Biomol Struct Dyn ; 35(7): 1547-1558, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27484103

RESUMO

A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.


Assuntos
Antivirais/farmacologia , Polifarmacologia , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Piranocumarinas/farmacologia , Piranos/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Antivirais/química , Feminino , Expressão Gênica , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/genética , Linfoma Relacionado a AIDS/patologia , Linfoma Relacionado a AIDS/virologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/virologia , Masculino , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Piranocumarinas/química , Piranos/química , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Biologia de Sistemas/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
20.
Int J Cancer ; 140(6): 1233-1245, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-27750386

RESUMO

The pathogenesis of classical Hodgkin lymphoma (cHL) is still enigmatic, largely because its tumor cells, the so-called Hodgkin and Reed-Stenberg (HRS) cells, invariably reside in a prominent reactive microenvironment, are rare and therefore difficult to analyze. On the other hand, the broadly investigated cHL-derived cell lines are not unequivocally considered as suitable and representative models for this puzzling disease. Based on current knowledge, it appears that the cross talk between the tumor cells and the reactive infiltrate of the microenvironment is complex and that multiple mechanisms occur, making cHL a very heterogeneous disease. In 20-40% of cHL cases, HRS cells carry a monoclonal infection by Epstein Barr virus (EBV), which is considered a tumor-initiating factor. In these cases, EBV shows a latency type II infection pattern with the expression of latent membrane protein-1 (LMP-1), a viral oncoprotein that mimics CD40 activation. This scenario is particularly intriguing for the pathogenesis of cHL arising in HIV-infected patients, which, for still obscure reasons, is invariably EBV-associated with LMP-1 expression in HRS cells. Recent evidences are consistent with the occurrence of different pathogenic pathways variably triggered by virus infections (EBV and HIV), genetic alterations, and interactions with critical microenvironmental components. This review focuses on the different microenvironmental niches that characterize cHL of the general population as well as cases of HIV-infected patients. A more comprehensive understanding of the complex interplay existing between HRS and tumor microenvironment is pivotal for the development of more effective treatments, particularly for relapsed or refractory diseases.


Assuntos
Infecções por Vírus Epstein-Barr/fisiopatologia , Doença de Hodgkin/virologia , Linfoma Relacionado a AIDS/virologia , Microambiente Tumoral , Proteínas da Matriz Viral/fisiologia , Antígenos CD/biossíntese , Antígenos CD/imunologia , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/virologia , Hibridização Genômica Comparativa , Citocinas/fisiologia , Receptor com Domínio Discoidina 1/fisiologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Fibroblastos/fisiologia , Regulação Neoplásica da Expressão Gênica , Doença de Hodgkin/classificação , Doença de Hodgkin/etiologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Humanos , Imunocompetência , Ativação Linfocitária , Linfócitos do Interstício Tumoral/imunologia , Linfoma Relacionado a AIDS/etiologia , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/patologia , Macrófagos/fisiologia , Modelos Biológicos , Proteínas de Neoplasias/fisiologia , Células de Reed-Sternberg/virologia , Transdução de Sinais , Latência Viral
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