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1.
Proc Natl Acad Sci U S A ; 119(27): e2122050119, 2022 07 05.
Article in English | MEDLINE | ID: mdl-35763571

ABSTRACT

AIDS-defining cancers declined after combined antiretroviral therapy (cART) introduction, but lymphomas are still elevated in HIV type 1 (HIV-1)-infected patients. In particular, non-Hodgkin's lymphomas (NHLs) represent the majority of all AIDS-defining cancers and are the most frequent cause of death in these patients. We have recently demonstrated that amino acid (aa) insertions at the HIV-1 matrix protein p17 COOH-terminal region cause protein destabilization, leading to conformational changes. Misfolded p17 variants (vp17s) strongly impact clonogenic B cell growth properties that may contribute to B cell lymphomagenesis as suggested by the significantly higher frequency of detection of vp17s with COOH-terminal aa insertions in plasma of HIV-1-infected patients with NHL. Here, we expand our previous observations by assessing the prevalence of vp17s in large retrospective cohorts of patients with and without lymphoma. We confirm the significantly higher prevalence of vp17s in lymphoma patients than in HIV-1-infected individuals without lymphoma. Analysis of 3,990 sequences deposited between 1985 and 2017 allowed us to highlight a worldwide increasing prevalence of HIV-1 mutants expressing vp17s over time. Since genomic surveillance uncovered a cluster of HIV-1 expressing a B cell clonogenic vp17 dated from 2011 to 2019, we conclude that aa insertions can be fixed in HIV-1 and that mutant viruses displaying B cell clonogenic vp17s are actively spreading.


Subject(s)
B-Lymphocytes , HIV Antigens , HIV-1 , Lymphoma, AIDS-Related , gag Gene Products, Human Immunodeficiency Virus , B-Lymphocytes/virology , Genetic Variation , HIV Antigens/genetics , HIV-1/genetics , HIV-1/isolation & purification , Humans , Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/virology , Prevalence , Retrospective Studies , gag Gene Products, Human Immunodeficiency Virus/genetics
2.
Blood Adv ; 6(5): 1420-1431, 2022 03 08.
Article in English | MEDLINE | ID: mdl-35026839

ABSTRACT

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with HIV (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCLs) in the modern antiretroviral therapy era. North American AIDS Cohort Collaboration on Research and Design and Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study, 52, 64, 101, 500, and 246 PWH with histologic confirmation of TCL, primary central nervous system lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphoma (DLBCL), and Hodgkin's lymphoma (HL), respectively, and 450 TCLs without HIV were eligible for analysis. At the time of TCL diagnosis, anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. Although PWH with TCL diagnosed between 1996 and 2009 experienced a low 5-year survival probability at 0.23 (95% confidence interval [CI]: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010 and 2016 (0.69; 95% CI: 0.48, 1; P = .04) in contrast to TCLs among PWoH (0.45; 95% CI: 0.41, 0.51; P = .53). Similarly, PWH with ALCLs diagnosed between 1996 and 2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; P = .09) and DLBCL (0.17; 95% CI: 0.06, 0.46; P = .11) and behind HL (0.57; 95% CI: 0.50, 0.65; P < .0001). Despite a small number, those diagnosed between 2010 and 2016 experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison with PWoH (0.76; 95% CI: 0.66, 0.87; P = .58). Thus, our analysis confirms improved overall survival for aggressive B- and T-cell malignancies among PWH in the last decade.


Subject(s)
Acquired Immunodeficiency Syndrome , Hodgkin Disease , Lymphoma, AIDS-Related , Lymphoma, Large B-Cell, Diffuse , Lymphoma, T-Cell, Peripheral , Hodgkin Disease/pathology , Humans , Lymphoma, AIDS-Related/epidemiology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/pathology , T-Lymphocytes/pathology
3.
AIDS Res Hum Retroviruses ; 38(2): 135-142, 2022 02.
Article in English | MEDLINE | ID: mdl-34652958

ABSTRACT

People living with HIV (PLHIV) have an increased risk of hematologic malignancies (HMs). We aimed to characterize HMs among PLHIV at Karolinska University Hospital, Stockholm, Sweden. We studied all PLHIV receiving care at our center between 2004 and 2018. Data were retrieved retrospectively from InfCareHIV database and medical records. Around 3,484 patients received HIV care for a total of 22,903 person-years (py) with median follow-up of 7.6 years. HMs were identified in 43 patients with 30 cases of non-Hodgkin lymphoma (NHL), 9 cases of Hodgkin lymphoma (HL), 2 multicentric Castleman's disease, and 1 case each of myeloma and myelodysplastic syndrome. The incidence rate of NHL was 88/105 py and HL 39.6/105 py. The incidence of NHL declined 2004-2010 versus 2011-2018 (180.8 vs. 40.1/105 py; p = .001). Median time from HIV diagnosis to malignancy was shorter in NHL compared with HL (1.2 years vs. 8.9 years; p = .01) and effective HIV treatment was less common in NHL (33% vs. 100%; p < .001). The 5-year survival rate of NHL was 59% and HL 43%, significantly lower compared with lymphoma survival in the general population in Sweden. In the era of effective antiretroviral therapy (ART), the incidence rate of lymphoma was more than five times higher in PLHIV and 5-year survival significantly inferior. Efforts for earlier identification of HIV-infected individuals are likely to affect the incidence of NHL. Additionally, an effective screening for clinical and laboratory signs of HL in PLHIV on ART should be introduced to improve identification and survival of HL in this population.


Subject(s)
HIV Infections , Hematologic Neoplasms , Hodgkin Disease , Lymphoma, AIDS-Related , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Hematologic Neoplasms/complications , Hematologic Neoplasms/epidemiology , Hodgkin Disease/complications , Hodgkin Disease/epidemiology , Humans , Incidence , Lymphoma, AIDS-Related/epidemiology , Retrospective Studies , Sweden/epidemiology
4.
Blood ; 139(7): 995-1012, 2022 02 17.
Article in English | MEDLINE | ID: mdl-34469512

ABSTRACT

HIV infection increases cancer risk and is linked to cancers associated to infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. Lymphomas represent one of the most frequent malignancies among individuals infected by HIV. Diffuse large B-cell lymphoma remains a leading cancer after the introduction of combined antiretroviral therapy (cART). The incidence of other lymphomas including Burkitt lymphoma, primary effusion lymphomas, and plasmablastic lymphoma of the oral cavity remain stable, whereas the incidence of Hodgkin lymphoma and Kaposi sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman disease has increased. The heterogeneity of lymphomas in individuals infected by HIV likely depends on the complexity of involved pathogenetic mechanisms (ie, HIV-induced immunosuppression, genetic abnormalities, cytokine dysregulation, and coinfection with the gammaherpesviruses Epstein-Barr virus and KSHV) and the dysregulation of the immune responses controlling these viruses. In the modern cART era, standard treatments for HIV-associated lymphoma including stem cell transplantation in relapsed/refractory disease mirror that of the general population. The combination of cART and antineoplastic treatments has resulted in remarkable prolongation of long-term survival. However, oncolytic and immunotherapic strategies and therapies targeting specific viral oncogenes will need to be developed.


Subject(s)
HIV Infections/complications , HIV/isolation & purification , Hematologic Neoplasms/pathology , Lymphoma, AIDS-Related/pathology , HIV Infections/virology , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/virology , Humans , Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/virology
5.
J Acquir Immune Defic Syndr ; 88(3): 252-260, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34354010

ABSTRACT

BACKGROUND: South Africa has a high HIV prevalence, which associates with an increased risk of lymphoma. Antiretroviral therapy (ART) became accessible in 2004, but the program has substantially expanded. Changes in lymphoma patterns are documented in high-income countries after wide-scale ART including declining high-grade B-cell non-Hodgkin lymphomas (HG B-NHLs), particularly diffuse large B-cell lymphoma, and increased Hodgkin lymphoma (HL). There are limited data from Africa. This study aimed to compare HG B-NHL characteristics in the early (2007) and later (2017) ART era. METHODS: All incident lymphomas at the National Health Laboratory Service, Johannesburg, were identified using the laboratory information system, and data were collected for each patient. RESULTS: The total number of lymphoma cases increased from 397 (2007) to 582 (2017). This was associated with improved lymphoma classification and patient referral for oncological care. HG B-NHL remained the most diagnosed lymphoma subtype in 2017 comprising 70% of HIV-associated lymphomas, followed by HL (24%). Diffuse large B-cell lymphoma comprised 65% of all HG B-NHLs and 45% of all lymphomas in people with HIV in 2017. Significantly more patients were on ART in 2017, with improvements in virological control documented. Despite this, 47.6% of patients were not virologically suppressed, and 37.5% of patients were ART-naive at time of diagnosis in 2017. Immunological reconstitution was suboptimal, which may reflect late initiation of ART. CONCLUSION: Public health initiatives to initiate ART as early as possible and to retain patients in ART programs may assist in decreasing the number of HIV-associated lymphomas in our setting.


Subject(s)
HIV Infections/complications , HIV Infections/drug therapy , Hodgkin Disease/epidemiology , Lymphoma, AIDS-Related/epidemiology , Adolescent , Adult , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Hodgkin Disease/drug therapy , Humans , Incidence , Lymphoma, AIDS-Related/diagnosis , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/epidemiology , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Non-Hodgkin/epidemiology , Male , Middle Aged , Retrospective Studies , South Africa/epidemiology , Young Adult
6.
AIDS ; 35(14): 2299-2309, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34231524

ABSTRACT

OBJECTIVE: To describe lymphoma in HIV-2-infected patients and compare their characteristics with lymphoma in HIV-1-infected patients. DESIGN: Ancillary analysis from a single center prospective cohort of HIV-lymphoma. METHODS: We report on 16 patients with HIV-2-lymphoma diagnosed after 1996 and included in a prospective cohort of HIV lymphoma. Five additional HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I (6 lymphomas) are separately reported. The incidence of lymphoma in HIV-2-infected patients was evaluated in the French multicentric HIV-2 cohort. RESULTS: Incidence of lymphoma in the French HIV-2 cohort was estimated as 0.6/1000 patient-years. In our series, the median CD4+ cell count was 166 × 106/l at the time of lymphoma diagnosis and 50% of patients had undetectable plasma HIV-2-RNA. Lymphomas were non-Hodgkin lymphoma (n = 12) and classical Hodgkin lymphoma (n = 4). Similarly to HIV-1-lymphoma, clinical presentation was aggressive in most cases. All but one patient received intensive chemotherapy. Complete remission was achieved in 13 cases and 1 patient relapsed. The overall survival was not statistically different from that observed in patients with HIV-1 lymphoma. The six additional lymphomas observed in five HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I presented with similar clinical presentation but worse prognosis. CONCLUSION: Despite the lower pathogenicity of HIV-2, the risk of developing lymphoma seems to be close to that observed in HIV-1 population with similar lymphoma characteristics. Compared with HIV-1, HIV-2-infected patients developed lymphoma later in their life but at a similar CD4+ cell count level.


Subject(s)
HIV Infections , Lymphoma, AIDS-Related , Antineoplastic Combined Chemotherapy Protocols , HIV Infections/complications , HIV Infections/drug therapy , HIV-2 , Humans , Lymphoma, AIDS-Related/drug therapy , Lymphoma, AIDS-Related/epidemiology , Prospective Studies
7.
Bull Cancer ; 108(10): 953-962, 2021 Oct.
Article in French | MEDLINE | ID: mdl-34246454

ABSTRACT

Lymphomas remain a leading cause of morbidity and mortality for HIV-positive patients. The most common lymphomas include diffuse large B-cell lymphoma, Burkitt lymphoma, primary effusion lymphoma, plasmablastic lymphoma and Hodgkin lymphoma. Appropriate approach is determined by lymphoma stage, performans status, comorbidities, histological subtype, status of the HIV disease and immunosuppression. Treatment outcomes have improved due to chemotherapy modalities and effective antiretroviral therapy. This review summarizes epidemiology, pathogenesis, pathology, and current treatment landscape in HIV associated lymphoma.


Subject(s)
HIV Infections/complications , Lymphoma, AIDS-Related/virology , Anti-HIV Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/pathology , Burkitt Lymphoma/virology , Castleman Disease/drug therapy , Castleman Disease/pathology , Castleman Disease/virology , HIV Infections/drug therapy , HIV Seropositivity/complications , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Hodgkin Disease/virology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunocompromised Host , Incidence , Lymphoma, AIDS-Related/drug therapy , Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/virology , Lymphoma, Primary Effusion/drug therapy , Lymphoma, Primary Effusion/pathology , Lymphoma, Primary Effusion/virology , Plasmablastic Lymphoma/drug therapy , Plasmablastic Lymphoma/pathology , Plasmablastic Lymphoma/virology , Prognosis , Recurrence
8.
J Infect Chemother ; 27(10): 1459-1464, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34158238

ABSTRACT

Introduction Lymphoma is the most common cancer in HIV/AIDS patients. Chemotherapy regiments recommended for lymphomas in HIV-negative patients are also used for lymphomas in HIV/AIDS patients. Little is known about the infections among HIV/AIDS patients with lymphoma undergoing chemotherapy. Methods This retrospective study investigated the incidence, spectrum of and risk factors for infections during chemotherapy in 164 HIV/AIDS patients with lymphoma admitted to Shanghai Public Health Clinical Center from July 2013 to December 2020. Results The median age of the patients was 43 years old; 90.9% (149/164) were male. A total of 112 (68.3%) patients had a CD4 count < 200 cells/µL at lymphoma diagnosis. Diffuse large B-cell lymphoma (56%, 91/164) and Burkitt lymphoma (28%, 46/164) were the two most common subtypes of lymphoma. Among the 137 patients who underwent chemotherapy (total cycles = 749), 58.4% (80/137) of patients experienced a total of 153 episodes of infection, with an incidence rate of 20.4% (153/749). The most commonly seen infections were lung infection (29.2%, 40/137) and febrile neutropenia (27.0%, 37/137). Multivariate analysis showed that grade 4 neutropenia during chemotherapy (OR = 7.128, 95% CI 3.051-16.654, p < 0.001) and duration of antiretroviral treatment at lymphoma diagnosis <6 months (OR = 3.520, 95% CI 1.432-8.653, p = 0.006) were independent risk factors for infection during chemotherapy. Conclusions A large proportion of HIV/AIDS patients with lymphoma may be at risk of infection during chemotherapy. Effective measures should be taken for patients with high risk factors to prevent the occurrence of infection.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Lymphoma, AIDS-Related , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/epidemiology , Adult , Antineoplastic Combined Chemotherapy Protocols , China/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Incidence , Lymphoma, AIDS-Related/drug therapy , Lymphoma, AIDS-Related/epidemiology , Male , Retrospective Studies
10.
Ocul Immunol Inflamm ; 29(3): 621-627, 2021 Apr 03.
Article in English | MEDLINE | ID: mdl-32453669

ABSTRACT

Purpose: To describe the epidemiology, clinical characteristics, diagnosis and treatment of human immunodeficiency virus (HIV)-related primary vitreoretinal lymphoma (PVRL).Methods: Narrative literature review.Results: HIV-related PVRL occurs in persons who are relatively young and generally have very low CD4+ T-cell counts. Vitritis with subretinal or sub-retinal pigment epithelial infiltrates is typical. Vitreous cytology remains the gold standard for diagnosis, supplemented by flow cytometry and genetic analyses of tumor cells, and measurement of aqueous or vitreous interleukin-10 levels. Concurrent brain involvement also may establish the diagnosis. Treatment includes antiretroviral therapy (ART), systemic chemotherapy (usually methotrexate-based) and local ocular treatment (intravitreal methotrexate, intravitreal rituximab, external beam radiotherapy). Systemic chemotherapy is of uncertain value for PVRL without other central nervous system involvement. Prognosis is poor, but has improved significantly compared to the pre-ART era.Conclusions: Ophthalmologists should consider the diagnosis of PVRL in HIV-positive individuals who present with intermediate or posterior uveitis.


Subject(s)
HIV Infections/complications , Intraocular Lymphoma/epidemiology , Lymphoma, AIDS-Related/epidemiology , Retinal Neoplasms/epidemiology , Vitreous Body/pathology , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Diagnosis, Differential , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Intraocular Lymphoma/diagnosis , Intraocular Lymphoma/drug therapy , Lymphoma, AIDS-Related/diagnosis , Lymphoma, AIDS-Related/drug therapy , Methotrexate/therapeutic use , Radiotherapy , Retinal Neoplasms/diagnosis , Retinal Neoplasms/drug therapy , Rituximab/therapeutic use , Vitrectomy
11.
Br J Haematol ; 190(3): 371-384, 2020 08.
Article in English | MEDLINE | ID: mdl-32080836

ABSTRACT

Little is known about the incidence of late effects following non-Hodgkin lymphoma (NHL) among adolescent and young adult (AYA, 15-39 years) survivors. Using data from the California Cancer Registry linked to hospital discharge, we estimated the cumulative incidence of late effects at 10 years among AYAs diagnosed with NHL during 1996-2012, who survived ≥2 years. Cox proportional-hazards models were used to investigate the influence of sociodemographic and clinical factors on the occurrence of late effects. Of 4392 HIV-uninfected patients, the highest incident diseases were: endocrine (18·5%), cardiovascular (11·7%), and respiratory (5·0%), followed by secondary primary malignancy (SPM, 2·6%), renal and neurologic (2·2%), liver/pancreatic (2·0%), and avascular necrosis (1·2%). Among the 425 HIV-infected survivors, incidence was higher for all late effects, especially over threefold increased risk of SPM, compared to HIV-uninfected patients (8·1% vs. 2·6%). In multivariable models for HIV-uninfected patients, public or no health insurance (vs. private), residence in lower socioeconomic neighbourhoods (vs. higher), and receipt of a haematopoietic stem cell transplant were associated with a greater risk of most late effects. Our findings of substantial incidence of late effects among NHL AYA survivors emphasise the need for longterm follow-up and appropriate survivorship care to reduce morbidity and mortality in this vulnerable population.


Subject(s)
Cancer Survivors , Chronic Disease/epidemiology , Lymphoma, AIDS-Related/epidemiology , Lymphoma, Non-Hodgkin/epidemiology , Adolescent , Adult , Cancer Survivors/statistics & numerical data , Cardiovascular Diseases/epidemiology , Digestive System Diseases/epidemiology , Endocrine System Diseases/epidemiology , Female , Humans , Incidence , Kidney Diseases/epidemiology , Neoplasms, Second Primary/epidemiology , Nervous System Diseases/epidemiology , Proportional Hazards Models , Registries , Respiratory Tract Diseases/epidemiology , Socioeconomic Factors , Young Adult
12.
Int J Cancer ; 146(11): 3134-3146, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32003460

ABSTRACT

People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause-specific mortality rates (MR) after diagnosis of specific cancers and compared 5-year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006-2015: ADMs 102 (95% CI 92-113) per 1,000 years versus 88 (78-100), viral NADMs 134 (106-169) versus 111 (93-133) and nonviral NADMs 264 (232-300) versus 226 (206-248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19-39%]), lung (18% [13-23%]) and cervical (75% [63-84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67-81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS.


Subject(s)
Acquired Immunodeficiency Syndrome/etiology , Hodgkin Disease/mortality , Liver Neoplasms/mortality , Lung Neoplasms/mortality , Lymphoma, AIDS-Related/mortality , Uterine Cervical Neoplasms/mortality , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/mortality , Adult , Female , France/epidemiology , Hodgkin Disease/complications , Hodgkin Disease/epidemiology , Humans , Liver Neoplasms/complications , Liver Neoplasms/epidemiology , Lung Neoplasms/complications , Lung Neoplasms/epidemiology , Lymphoma, AIDS-Related/complications , Lymphoma, AIDS-Related/epidemiology , Middle Aged , Prognosis , Survival Rate , United Kingdom/epidemiology , Uterine Cervical Neoplasms/complications , Uterine Cervical Neoplasms/epidemiology
14.
Cancer Med ; 9(2): 552-561, 2020 01.
Article in English | MEDLINE | ID: mdl-31782984

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/blood , DNA, Viral/blood , Epstein-Barr Virus Infections/complications , HIV Infections/complications , Herpesvirus 4, Human/genetics , Lymphoma, AIDS-Related/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Adult , Aged , DNA, Viral/genetics , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/virology , Female , Follow-Up Studies , HIV/isolation & purification , HIV Infections/blood , HIV Infections/diagnosis , HIV Infections/virology , Herpesvirus 4, Human/isolation & purification , Humans , Lymphoma, AIDS-Related/blood , Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/virology , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Large B-Cell, Diffuse/virology , Malawi/epidemiology , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate , Young Adult
15.
AIDS Res Hum Retroviruses ; 36(5): 381-388, 2020 05.
Article in English | MEDLINE | ID: mdl-31789046

ABSTRACT

Infection with human immunodeficiency virus (HIV) is associated with substantially increased incidence of non-Hodgkin lymphoma (NHL). This risk may be driven, in part, by reduced immune control over viral infections in the setting of acquired immunodeficiency syndrome (AIDS), although the lymphomagenic mechanisms are not yet established. We used bead-based multiplex assays to measure antibody seroreactivity to 32 viral antigens representing 22 different viral infections (human herpesviruses 1-8, hepatitis B and C virus, human T-lymphotropic virus type-1, and human polyomaviruses) in two prospective HIV cohorts. Incident (n = 28) and prevalent (n = 38) AIDS-related NHL cases were matched by age, sex, race, and CD4 count to 67 HIV-positive control individuals without AIDS-NHL. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of AIDS-NHL with the number of different viruses to which an individual was seropositive and seroreactivity to individual antigens. Seropositivity to an increasing number of viruses was inversely associated with AIDS-NHL (OR per virus = 0.84, 95% CI = 0.72-0.98). Seroreactivity to herpes simplex virus 2 2mgG unique antigen (OR = 0.47; 95% CI = 0.23-0.97) and to WU polyomavirus viral capsid protein (OR = 0.26, 95% CI = 0.10-0.65) was significantly lower in AIDS-NHL cases compared to controls. In this evaluation of antibodies to multiple viruses, we observed an inverse association between seropositivity to a larger number of viruses and AIDS-NHL. While in need of further evaluation, our data raise the novel hypothesis that insufficient exposures or impaired humoral immune responses to viral infections may be associated with AIDS-related lymphomagenesis.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Antibodies, Viral/blood , HIV Seropositivity/blood , Lymphoma, AIDS-Related/epidemiology , Viruses/immunology , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/immunology , Adult , Case-Control Studies , Female , Humans , Incidence , Male , Middle Aged , Odds Ratio , Prospective Studies , Risk Factors , Viruses/classification
16.
Medicine (Baltimore) ; 98(26): e16129, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31261533

ABSTRACT

Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.


Subject(s)
Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/therapy , Adult , Antineoplastic Agents/therapeutic use , Burkitt Lymphoma/epidemiology , Burkitt Lymphoma/pathology , Burkitt Lymphoma/therapy , Female , Humans , Lymphoma, AIDS-Related/pathology , Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/therapy , Male , Neoplasm Staging , Retrospective Studies
17.
Int J Hematol ; 110(2): 244-249, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31111394

ABSTRACT

This retrospective nationwide study sought to clarify the current status of human immunodeficiency virus (HIV)-associated lymphoma in Japan, where the number of new HIV infections remains high. We extracted data of patients with HIV-associated lymphoma who were registered in the database of the Japanese Society of Hematology Blood Disease Registry from January 2012 to December 2015, and analyzed patient characteristics, pathological diagnosis, and outcomes. The study cohort included 79 patients, including 75 male patients, with a median age of 52.5 (25-88) years. Among the lymphoma subtypes reported, the most common was diffuse large B cell lymphoma (DLBCL), followed by Burkitt lymphoma and primary central nervous system lymphoma. Estimated 3-year overall survival (OS) of all types of HIV-associated lymphoma was 68.8% [95% CI 68.2-69.4%]. However, the rate of extranodal involvement at the time of diagnosis was 49.2% and half of DLBCL was international prognostic index high or high-intermediate, with poor prognosis. Patients with primary effusion lymphoma died within 6 months. Even in an era of combination antiretroviral therapy, HIV-associated lymphoma remains an important problem. Clinical manifestations identified in this study were aggressive, and outcomes remained poor, warranting continuous surveillance of HIV-associated lymphoma.


Subject(s)
Lymphoma, AIDS-Related/epidemiology , Adult , Aged , Aged, 80 and over , Anti-HIV Agents/therapeutic use , Burkitt Lymphoma/epidemiology , Central Nervous System Neoplasms/epidemiology , Female , Humans , Japan/epidemiology , Kaplan-Meier Estimate , Lymphoma, B-Cell/epidemiology , Lymphoma, T-Cell/epidemiology , Male , Middle Aged , Registries , Retrospective Studies , Treatment Outcome
19.
J Glob Oncol ; 4: 1-11, 2018 09.
Article in English | MEDLINE | ID: mdl-30241264

ABSTRACT

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.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Lymphoma, AIDS-Related/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Botswana/epidemiology , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Female , HIV Infections/complications , HIV Infections/epidemiology , HIV Infections/virology , Humans , Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/virology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/virology , Male , Middle Aged , Prednisone/therapeutic use , Prospective Studies , Rituximab/therapeutic use , Treatment Outcome , United States/epidemiology , Vincristine/therapeutic use
20.
Int J Cancer ; 143(6): 1348-1355, 2018 09 15.
Article in English | MEDLINE | ID: mdl-29663358

ABSTRACT

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.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/complications , HIV/isolation & purification , Hodgkin Disease/epidemiology , Lymphoma, AIDS-Related/epidemiology , Adolescent , Adult , Aged , Case-Control Studies , Female , Follow-Up Studies , HIV Infections/drug therapy , HIV Infections/virology , Hodgkin Disease/virology , Humans , Incidence , Lymphoma, AIDS-Related/virology , Male , Middle Aged , Prognosis , Rwanda/epidemiology , Survival Rate , Young Adult
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