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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.

Emerging evidence shows that tumor cells secrete extracellular vesicles (EVs) that carry bioactive cell surface markers, such as programmed death-ligand 1 (PD-L1), which can modulate immune responses and inhibit anti-tumor responses, potentially playing a role in lymphomagenesis and in promoting the growth of these cancers. In this study, we investigated the role of EVs expressing cell surface molecules associated with B cell activation and immune regulation. We measured levels of EVs derived from plasma from 57 subjects with AIDS-related non-Hodgkin lymphoma (AIDS-NHL) enrolled in the AIDS Malignancies Consortium (AMC) 034 clinical trial at baseline and post-treatment with rituximab plus concurrent infusional EPOCH chemotherapy. We found that plasma levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII were significantly reduced after cancer treatment. AIDS-NHL patients with the diffuse large B cell lymphoma (DLBCL) tumor subtype had decreased plasma levels of EVs bearing PD-L1, compared to those with Burkitt's lymphoma. CD40, CD40L and TNF-RII-expressing EVs showed a significant positive correlation with plasma levels of IL-10, CXCL13, sCD25, sTNF-RII and IL-18. Our results suggest that patients with AIDS-NHL have higher levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII in circulation before cancer treatment and that levels of these EVs are associated with levels of biomarkers of microbial translocation and inflammation.

PurposeAIDS-related non-Hodgkin lymphoma (ARL) is the most common cancer in HIV-infected individuals in the United States and other countries in which HIV-positive persons have access to effective combination antiretroviral therapy (cART). Our prior work showed that pretreatment/postdiagnosis plasma levels of some cytokines, such as IL6, IL10, and CXCL13, have the potential to serve as indicators of clinical response to treatment and survival in ARL. The aims of this study were to identify novel prognostic biomarkers for response to treatment and/or survival in persons with ARL, including biomarkers of microbial translocation and inflammation.Experimental designWe quantified plasma levels of several biomarkers (sCD14, LBP, FABP2, EndoCab IgM, IL18, CCL2/MCP-1, sCD163, IP-10/CXCL10, TARC/CCL17, TNFα, BAFF/BLyS, sTNFRII, sCD44, and sIL2Rα/sCD25) by multiplexed immunometric assays (Luminex) or ELISA in plasma specimens obtained from ARL patients enrolled in the AMC-034 trial, which compared infusional combination chemotherapy (EPOCH: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with concurrent or sequential rituximab. Plasma was collected prior to the initiation of therapy (n = 57) and after treatment initiation (n = 55).ResultsWe found that several biomarkers decreased significantly after treatment, including TNFα, sCD25, LBP, and TARC (CCL17). Moreover, pretreatment plasma levels of BAFF, sCD14, sTNFRII, and CCL2/MCP-1 were univariately associated with overall survival, and pretreatment levels of BAFF, sTNFRII, and CCL2/MCP-1 were also associated with progression-free survival.ConclusionsOur results suggest that patients with ARL who responded to therapy had lower pretreatment levels of inflammation and microbial translocation as compared with those who did not respond optimally.

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.

Background: We aimed to investigate whether susceptibility-weighted imaging (SWI) and contrast-enhanced 3D-T1WI can differentiate Acquired Immune Deficiency Syndrome-Related Primary Central Nervous System Lymphoma (AR-PCNSL) from cerebral toxoplasmosis. Methods: This was a prospective cohort study. 20 AIDS patients were divided into AR-PCNSL group (13 cases) and cerebral toxoplasmosis group (7 cases) based on pathology results. We analyzed the appearance of lesions on SWI and enhanced 3D T1WI and ROC curves in the diagnosis of AR-PCNSL and cerebral toxoplasmosis. Results: Cerebral toxoplasmosis was more likely to show annular enhancement (p = 0.002) and complete smooth ring enhancement (p = 0.002). It was also more likely to present a complete, smooth low signal intensity rim (LSIR) (p = 0.002) and an incomplete, smooth LSIR (p = 0.019) on SWI. AR-PCNSL was more likely to present an incomplete, irregular LSIR (p

Many preclinical studies of infectious diseases have neglected experimental designs that evaluate potential differences related to sex with a concomitant over-reliance on male model systems. Hence, the NIH implemented a monitoring system for sex inclusion in preclinical studies. Methods: Per this mandate, we examined the lung burdens of Pneumocystis murina infection in three mouse strains in both male and female animals at early, mid, and late time points. Results: Females in each strain had higher infection burdens compared to males at the later time points. Conclusion: Females should be included in experimental models studying Pneumocystis spp. [ABSTRACT FROM AUTHOR]

Radiotherapy is not usually a part of standard Burkitt lymphoma treatment. We aim to assess patient and treatment characteristics of Burkitt lymphoma, particularly RT use, and how they relate to survival. Retrospective cohort of adult patients treated from 2008 to 2019 in an academic hospital. All patients had biopsy-proven Burkitt's lymphoma staged I to IV according to St. Jude's/Murphy staging system. Patients were followed for at least six-months or until death. Forty-eight consecutive patients were selected. Median age at diagnosis was 36.9 years (18–62). Median follow-up was 7.78 months (0.5–187.5). Most were male (81.3%) and had good performance by ECOG scale on their first hematologist appointment (56.2% were ECOG 0). Median OS and PFS were 8.4 months (interquartile range Q1-Q3: 3.96–152.2) and 8.3 months (interquartile range Q1-Q3: 6.7-not reached), respectively, with 32 deaths. A total of 43 patients (89.6%) were HIV-positive and had a median CD4 + level of 193.5 cells/mm3 at diagnosis. Patients that did not present a drop in CD4 + levels after treatment had better OS than those that did (p = 0.020). 11 patients underwent radiotherapy (22.9%) who had better OS than those who did not (p = 0.015). Our findings show that adult patients living with HIV presenting Burkitt lymphoma who maintained their immune status throughout treatment had better prognosis than those who presented CD4 + cells drops. Also, patients treated with radiotherapy—either with palliative intent or as consolidation after chemotherapy—had statistically significant better OS than those not irradiated. Prospective data is warranted for radiotherapy as a consolidative and as a palliative treatment. [ABSTRACT FROM AUTHOR]

BackgroundThe optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.MethodsTo identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).ResultsWe provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4

Abstract Background Patients with acquired immune deficiency syndrome (AIDS) often suffer from opportunistic infections and related primary central nervous system lymphoma (AR-PCNSL). Both diseases showed multiple ring enhancement lesions in conventional magnetic resonance (MR). It is very difficult to make the differential diagnosis. We aimed to investigate whether multimodal MR (diffusion weighted imaging (DWI)/ apparent diffusion coefficient (ADC), 3D pseudo-continuous arterial spin labeling (3D-pCASL) and susceptibility-weighted imaging (SWI)) combined with conventional MR can differentiate AR-PCNSL from infections. Methods This was a prospective study. We recruited 19 AIDS patients who were divided into AR-PCNSL group (9 cases) and infection group (10 cases) by pathological results. We analyzed whether there was statistical (Fisher’s method) difference in multimodal MR between the two groups. We analyzed whether multimodal MR combined with conventional MR could improve the diagnosis of AR-PCNSL. Results The lesions were more likely involved the paraventricular (0.020) and corpus callosum (0.033) in AR-PCNSL group in conventional MR. In multimodal MR, AR-PCNSL group showed low ADC value, with p values of 0.001. Infection group more inclined to high ADC value, with p was 0.003. In multimodal MR, AR-PCNSL group had more low signal intensity (grade 2–3) in the degree of intratumoral susceptibility signal intensity in SWI (SWI-ITSS), with p values of 0.001. The sensitivity, specificity of conventional MR in the diagnosis of AR-PCNSL was 88.9 and 70.0%. The conventional MR sequence combined with DWI/ADC sequence in the diagnosis of AR-PCNSL had a sensitivity of 100.0%, and a specificity of 60.0%. The sensitivity and specificity of the conventional MR sequence combined with the SWI-ITSS sequence in the diagnosis of AR-PCNSL were 100 and 70.0%. The conventional MR combined with ADC or SWI-ITSS improved the diagnosis of AR-PCNSL. Conclusion Multimodal MR could distinguish AR-PCNSL from infectious lesions. The multimodal MR (DWI/ADC or SWI-ITSS) combined with conventional MR could improve the diagnosis of AR-PCNSL. The ADC value should be attached importance in clinical work. When distinguishing AR-PCNSL from toxoplasmosis or tuberculoma, SWI should be used to obtain a correct diagnosis.

PurposeThe aims of this study were to determine whether pretreatment plasma levels of cytokines and immune activation-associated molecules changed following treatment for AIDS-NHL with rituximab plus infusional EPOCH, and to determine whether pretreatment levels of these molecules were associated with response to treatment and/or survival.Experimental designWe quantified plasma levels of B-cell activation-associated molecules (sCD27, sCD30, and sCD23) and cytokines (IL6, IL10, and CXCL13) before and after the initiation of treatment in persons with AIDS-NHL (n = 69) in the AIDS Malignancies Consortium (AMC) 034 study, which evaluated treatment of AIDS-NHL with EPOCH chemotherapy and rituximab.ResultsTreatment resulted in decreased plasma levels of some of these molecules (CXCL13, sCD27, and sCD30), with decreased levels persisting for one year following the completion of treatment. Lower levels of CXCL13 before treatment were associated with complete responses following lymphoma therapy. Elevated levels of IL6 pretreatment were associated with decreased overall survival, whereas higher IL10 levels were associated with shorter progression-free survival (PFS), in multivariate analyses. Furthermore, patients with CXCL13 or IL6 levels higher than the median levels for the NHL group, as well as those who had detectable IL10, had lower overall survival and PFS, in Kaplan-Meier analyses.ConclusionsThese results indicate that CXCL13, IL6, and IL10 have significant potential as prognostic biomarkers for AIDS-NHL.

• SWI and CE 3D-T1WI were useful in AR-PCNSL and cerebral toxoplasmosis. • AR-PCNSL showed a higher SWI-ILSS and larger 3D-T1WI volume enhancement. • AR-PCNSL was more likely to present incomplete, irregular LSIRs and CLSI on SWI. • Cerebral toxoplasmosis was more likely to present smooth LSIRs on SWI. We aimed to investigate whether susceptibility-weighted imaging (SWI) and contrast-enhanced 3D-T1WI can differentiate Acquired Immune Deficiency Syndrome-Related Primary Central Nervous System Lymphoma (AR-PCNSL) from cerebral toxoplasmosis. This was a prospective cohort study. 20 AIDS patients were divided into AR-PCNSL group (13 cases) and cerebral toxoplasmosis group (7 cases) based on pathology results. We analyzed the appearance of lesions on SWI and enhanced 3D T1WI and ROC curves in the diagnosis of AR-PCNSL and cerebral toxoplasmosis. Cerebral toxoplasmosis was more likely to show annular enhancement (p = 0.002) and complete smooth ring enhancement (p = 0.002). It was also more likely to present a complete, smooth low signal intensity rim (LSIR) (p = 0.002) and an incomplete, smooth LSIR (p = 0.019) on SWI. AR-PCNSL was more likely to present an incomplete, irregular LSIR (p < 0.001) and irregular central low signal intensity (CLSI) (p<0.001) on SWI. The areas under the ROC curve of the SWI-ILSS grade and enhanced volume on 3D-T1WI were 0.872 and 0.862, respectively. A higher SWI-ILSS grade and larger 3D-T1WI volume enhancement were diagnostic for AR-PCNSL. SWI and CE 3D-T1WI were useful in the differential diagnosis of AR-PCNSL and cerebral toxoplasmosis. [ABSTRACT FROM AUTHOR]

Background: A substantial number of older adults succumb soon after HIV diagnosis despite ART. We explored the causes, risk factors and circumstances before death among older adults acquring HIV., Methods: We recruited individuals newly diagnosed at our centre from 2016-2020 and analysed data of those who died. Patients were stratified to older (≥50 years) or younger (<50 years) based on their age at diagnosis and attributes were compared. The Cox proportional multivariable model was used to identify factors associated with all-cause mortality., Results: Among 75 deaths reported, the majority of deaths were AIDS-related and late presentation was common in both age groups. The majority of deaths occurred in the first 12 months after care presentation and over two-thirds in both groups disengaged from care prior to death. Older age remained an independent factor associated with death after adjusting for confounders including opportunistic infections, late presentation to care, ART initiation and chronic comorbidities at presentation., Conclusion: Most causes of death in our setting were AIDS-related and associated with late care presentation both in young and older individuals, although older age at diagnosis remained an independent risk factor. Our findings highlight the urgent need to encourage prompt ART initiation following diagnosis, especially in older adults., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Many preclinical studies of infectious diseases have neglected experimental designs that evaluate potential differences related to sex with a concomitant over-reliance on male model systems. Hence, the NIH implemented a monitoring system for sex inclusion in preclinical studies. Methods: Per this mandate, we examined the lung burdens of Pneumocystis murina infection in three mouse strains in both male and female animals at early, mid, and late time points. Results: Females in each strain had higher infection burdens compared to males at the later time points. Conclusion: Females should be included in experimental models studying Pneumocystis spp.

OBJECTIVE: To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL). DESIGN: Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months). METHODS: A total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility. RESULTS: Higher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively. CONCLUSIONS: Altered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.

ObjectiveTo determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).DesignSerum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).MethodsA total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility.ResultsHigher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively.ConclusionsAltered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.

BackgroundHIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood.MethodsIn this study, serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1 to 5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV(+) controls from the Multicenter AIDS Cohort Study (MACS).ResultsMultivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), interleukin (IL)-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α were elevated in those HIV(+) individuals who went on to develop AIDS-NHL. In addition, the fraction of specimens with detectable IL-2 was increased and the fraction with detectable IL-4 was decreased in these subjects.ConclusionsThese results suggest that long-term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV(+) individuals.ImpactFLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α may serve as biomarkers for AIDS-NHL. .

ObjectiveAIDS-related primary central nervous system lymphoma (AR-PCNSL) has a poor prognosis. Improved understanding of specific patient, infectious, diagnostic, and treatment-related factors that affect overall survival (OS) is required to improve outcomes.DesignPopulation-based registry linkage study.MethodsAdult cases from the San Francisco AIDS registry (1990-2000) were matched with the California Cancer Registry (1985-2002) to ascertain AR-PCNSL data. Survival time was assessed through 31 December 2007. Risk factors and temporal trends for death were measured using two-sided Kaplan-Meier and Cox analyses.ResultsTwo hundred and seven AR-PCNSL patients were identified: 68% were white, 20% Hispanic, 10% African-American, and 2% Asian. Nineteen percent of patients had central nervous system (CNS) opportunistic infections diagnosed prior to AR-PCNSL. Fifty-seven percent of patients received radiation and/or chemotherapy and 12% used HAART prior to or within 30 days of AR-PCNSL diagnosis. One hundred and ninety-nine patients died (34 deaths/100 person-years). In adjusted analysis, prior CNS opportunistic infection diagnosis increased risk of death (hazard ratio 1.9, P = 0.0006) whereas radiation and/or chemotherapy decreased risk (hazard ratio 0.6, P

The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median pre-chemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. Clinical trials registration unique identifier: NCT00001137.

BackgroundThere is increasing evidence that chronic immune activation predisposes to non-Hodgkin lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the United States who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined.MethodsWe conducted a nested case-control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3 to 5 years, 1 to 3 years, and 0 to 1 year before AIDS-NHL diagnosis (n = 22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4(+) T-cell count, and study follow-up time (n = 78). ORs and 95% confidence intervals (CI) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models.ResultsElevated levels of sCD27 (OR = 7.21; 95% CI, 2.62-19.88), sCD30 (OR = 2.64; 95% CI, 1.24-5.64), and CXCL13 (OR = 2.56; 95% CI, 1.32-4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a two to three-fold increased risk of AIDS-NHL in certain subgroups, whereas elevated interleukin 6 was associated with a two-fold increased risk in the 0 to 1 year time-window, only.ConclusionsThese findings support the hypothesis that chronic B-cell activation contributes to the development of AIDS-NHL in women.ImpactSoluble CD23 (sCD23), sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL.

BACKGROUND: AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype. METHODS: Stored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry. RESULTS: An elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV- controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis. CONCLUSIONS: These results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection-associated B-cell activation, potentially contributing to the genesis of AIDS-NHL.

BackgroundAIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype.MethodsStored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry.ResultsAn elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV- controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis.ConclusionsThese results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection-associated B-cell activation, potentially contributing to the genesis of AIDS-NHL.

ObjectiveTo examine the association between early HIV viremia and mortality after HIV-associated lymphoma.DesignMulticenter observational cohort study.SettingCenter for AIDS Research Network of Integrated Clinical Systems cohort.ParticipantsHIV-infected patients with lymphoma diagnosed between 1996 and 2011, who were alive 6 months after lymphoma diagnosis and with at least two HIV RNA values during the 6 months after lymphoma diagnosis.ExposureCumulative HIV viremia during the 6 months after lymphoma diagnosis, expressed as viremia copy-6-months.Main outcome measureAll-cause mortality between 6 months and 5 years after lymphoma diagnosis.ResultsOf 224 included patients, 183 (82%) had non-Hodgkin lymphoma (NHL) and 41 (18%) had Hodgkin lymphoma. At lymphoma diagnosis, 105 (47%) patients were on antiretroviral therapy (ART), median CD4⁺ cell count was 148 cells/μl (interquartile range 54-322), and 33% had suppressed HIV RNA (

BackgroundLymphoma is the leading cause of cancer-related death among HIV-infected patients in the antiretroviral therapy (ART) era.MethodsWe studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems from 1996 until 2010. We examined differences stratified by histology and diagnosis year. Mortality and predictors of death were analyzed using Kaplan-Meier curves and Cox proportional hazards.ResultsOf 23 050 HIV-infected individuals, 476 (2.1%) developed lymphoma (79 [16.6%] Hodgkin lymphoma [HL]; 201 [42.2%] diffuse large B-cell lymphoma [DLBCL]; 56 [11.8%] Burkitt lymphoma [BL]; 54 [11.3%] primary central nervous system lymphoma [PCNSL]; and 86 [18.1%] other non-Hodgkin lymphoma [NHL]). At diagnosis, HL patients had higher CD4 counts and lower HIV RNA than NHL patients. PCNSL patients had the lowest and BL patients had the highest CD4 counts among NHL categories. During the study period, CD4 count at lymphoma diagnosis progressively increased and HIV RNA decreased. Five-year survival was 61.6% for HL, 50.0% for BL, 44.1% for DLBCL, 43.3% for other NHL, and 22.8% for PCNSL. Mortality was associated with age (adjusted hazard ratio [AHR] = 1.28 per decade increase, 95% confidence interval [CI] = 1.06 to 1.54), lymphoma occurrence on ART (AHR = 2.21, 95% CI = 1.53 to 3.20), CD4 count (AHR = 0.81 per 100 cell/µL increase, 95% CI = 0.72 to 0.90), HIV RNA (AHR = 1.13 per log10copies/mL, 95% CI = 1.00 to 1.27), and histology but not earlier diagnosis year.ConclusionsHIV-associated lymphoma is heterogeneous and changing, with less immunosuppression and greater HIV control at diagnosis. Stable survival and increased mortality for lymphoma occurring on ART call for greater biologic insights to improve outcomes.

Currently, few rodent models of AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) exist. In these studies, a novel mouse/human xenograft model of AIDS-associated Burkitt lymphoma (AIDS-BL) was created by injecting cells of the human AIDS-BL cell line, 2F7, intraperitoneally into NOD-SCID mice. Mice developed tumors in the peritoneal cavity, with metastases to the spleen, thymus, and mesenteric lymph nodes. Expression of the chemokine receptor, CXCR5, was greatly elevated in vivo on BL tumor cells in this model, as shown by flow cytometry. CXCL13 is the ligand for CXCR5, and serum and ascites levels of murine, but not human, CXCL13 showed a striking elevation in tumor-bearing mice, with levels as high as 200,000 pg/ml in ascites, as measured by ELISA. As shown by immunohistochemistry, murine CXCL13 was associated with macrophage-like tumor-infiltrating cells that appeared to be histiocytes. Blocking CXCR5 on 2F7 cells with neutralizing antibodies prior to injection into the mice substantially delayed tumor formation. The marked elevations in tumor cell CXCR5 expression and in murine CXCL13 levels seen in the model may potentially identify an important link between tumor-interacting histiocytes and tumor cells in AIDS-BL. These results also identify CXCL13 as a potential biomarker for this disease, which is consistent with previous studies showing that serum levels of CXCL13 were elevated in human subjects who developed AIDS-lymphoma. This mouse model may be useful for future studies on the interactions of the innate immune system and AIDS-BL tumor cells, as well as for the assessment of potential tumor biomarkers for this disease.

Background: Patients with acquired immune deficiency syndrome (AIDS) often suffer from opportunistic infections and related primary central nervous system lymphoma (AR-PCNSL). Both diseases showed multiple ring enhancement lesions in conventional magnetic resonance (MR). It is very difficult to make the differential diagnosis. We aimed to investigate whether multimodal MR (diffusion weighted imaging (DWI)/ apparent diffusion coefficient (ADC), 3D pseudo-continuous arterial spin labeling (3D-pCASL) and susceptibility-weighted imaging (SWI)) combined with conventional MR can differentiate AR-PCNSL from infections.Methods: This was a prospective study. We recruited 19 AIDS patients who were divided into AR-PCNSL group (9 cases) and infection group (10 cases) by pathological results. We analyzed whether there was statistical (Fisher's method) difference in multimodal MR between the two groups. We analyzed whether multimodal MR combined with conventional MR could improve the diagnosis of AR-PCNSL.Results: The lesions were more likely involved the paraventricular (0.020) and corpus callosum (0.033) in AR-PCNSL group in conventional MR. In multimodal MR, AR-PCNSL group showed low ADC value, with p values of 0.001. Infection group more inclined to high ADC value, with p was 0.003. In multimodal MR, AR-PCNSL group had more low signal intensity (grade 2-3) in the degree of intratumoral susceptibility signal intensity in SWI (SWI-ITSS), with p values of 0.001. The sensitivity, specificity of conventional MR in the diagnosis of AR-PCNSL was 88.9 and 70.0%. The conventional MR sequence combined with DWI/ADC sequence in the diagnosis of AR-PCNSL had a sensitivity of 100.0%, and a specificity of 60.0%. The sensitivity and specificity of the conventional MR sequence combined with the SWI-ITSS sequence in the diagnosis of AR-PCNSL were 100 and 70.0%. The conventional MR combined with ADC or SWI-ITSS improved the diagnosis of AR-PCNSL.Conclusion: Multimodal MR could distinguish AR-PCNSL from infectious lesions. The multimodal MR (DWI/ADC or SWI-ITSS) combined with conventional MR could improve the diagnosis of AR-PCNSL. The ADC value should be attached importance in clinical work. When distinguishing AR-PCNSL from toxoplasmosis or tuberculoma, SWI should be used to obtain a correct diagnosis. [ABSTRACT FROM AUTHOR]

PurposeEpstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.Experimental designHIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.ResultsSeventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].ConclusionOur results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs.

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples.

ObjectiveChronic inflammation and B-cell hyperactivation are seen in HIV infection, contributing to an increased risk for the accrual of genetic errors that may result in B-cell lymphoma. The primary objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) on serum levels of molecules that are associated with immune activation and/or inflammation, including several that are associated with B-cell activation, specifically IL-6, sCD30, sCD27, IgG, IgA, CXCL13 (B lymphocyte chemoattractant, BLC), a B-lymphocyte chemokine involved in B-cell trafficking, as well as C-reactive protein, an acute-phase protein.DesignWe used a retrospective cohort study design, measuring serum levels of these markers at each of four 1-year intervals, 2 years before and 2 years after HAART initiation, in a subgroup of 290 HIV-infected men enrolled in the Multicenter AIDS Cohort Study (MACS).MethodsSerum levels of immune activation-associated molecules were measured by ELISA and multiplexed immunometric assays. Reference values were determined by the 5th to 95th percentiles from a sample of 109 HIV-uninfected MACS men.ResultsHAART use was associated with a reduction, but not normalization, of most biomarkers tested. Serum levels of IL-6 and C-reactive protein appeared to be unaffected by HAART.ConclusionsThese results suggest a partial normalization of serum cytokine levels post HAART. However, a chronic state of B-cell hyperactivation continues 2-3 years after HAART initiation. These findings may explain, in part, the excess incidence of lymphoma still occurring in HIV-infected persons in the post-HAART era.

ObjectiveWe sought to determine the accuracy of cancer registry data regarding the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) status of patients with non-Hodgkin's lymphoma (NHL).MethodsWe used the population-based San Diego/Orange County cancer registry to identify 392 patients with HIV-related NHL diagnosed 1994-1999. After matching for age, sex, race, period of NHL diagnosis, and hospital type, we were able to find 324 corresponding patients among the remaining 4,863 NHL patients diagnosed 1994-1999 (who did not have HIV infection according to cancer registry records). We sought to review these patients' charts at 41 hospitals with 15 separate institutional review boards to determine if the HIV serostatus from the cancer registry was correct. We performed a forward conditional multivariate logistic regression to determine characteristics associated with a false positive HIV status.ResultsThe false positive rate was 8% while the false negative rate was 3%. The positive predictive value was 93% while the negative predictive value was 97%. Compared to correctly identified patients, false positives were more likely to be > or =50 years old, female, and treated with chemotherapy and less likely to be single with high grade or extranodal disease.ConclusionUsing cancer registry data to identify AIDS-related NHL is a valid research practice.

We used the San Diego/Orange County cancer registry to identify 64 cases of systemic non-Hodgkin's lymphoma (NHL) with AIDS who received highly active antiretroviral therapy (HAART) at the time of NHL diagnosis or thereafter and 64 NHL controls without AIDS, matched on age, sex, race, time of NHL diagnosis (1994-1995 and 1996-1999), and hospital type (academic, large community, and small community). We compared cases and controls by chi-squared tests and Kaplan-Meier methods. Thirty-three percent of cases had high grade histology versus 11% of controls (p < 0.01); 69% had baseline hemoglobin

Abstract: Plasmablastic lymphoma is a rare subtype of diffuse large B-cell lymphoma more frequently diagnosed in immunosuppressed patients, mainly HIV-infected. Primary cutaneous plasmablastic lymphoma is extremely rare, and in this patient it was the first clinical manifestation of unsuspected HIV-infection.

Objective: Rare disease Background: Immunosuppressive diseases and therapies have long been connected to risk of malignancies, especially lymphoma. With some diseases and drugs, the association is well established but the data is mostly anecdotal because of the rarity of the situation. Case Reports: We present 2 rare cases. The first patient had psoriasis, was on etanercept, and developed Hodgkin's lymphoma. This case is rare because psoriasis and etanercept do not usually cause lymphoma, and if they do, it is predominantly Epstein-Barr virus-positive non-Hodgkin's lymphoma. The second patient had acquired immune deficiency syndrome (AIDS) and developed Hodgkin's lymphoma while on highly active antiretroviral therapy (HAART). This case is rare because AIDS mostly causes Kaposi's sarcoma or non-Hodgkin's lymphoma due to immunosuppression, but whether it is AIDS or HAART therapy that leads to development of Hodgkin's lymphoma in these patients is not clear. Conclusions: Immunosuppression seems to be the primary culprit leading to lymphomas in these cases. The exact mechanism is still not completely understood. [ABSTRACT FROM AUTHOR]

HIV infection is known to be associated with the development of a wide range of neoplasia. About 25 to 40% of HIV-positive patients will present some kind of malignancy in the course of the disease; among them 10% are non-Hodgkin lymphomas (NHL) and 20% of these are represented by the diffuse large B-cell lymphoma. HIV-positive patients have a relative risk of 110 times higher to develop neoplasia, than the non-infected population. The gastrointestinal (GI) tract is the most frequent extranodal site of involvement. However, the primary GI lymphoma is rare. The authors present a case of a 31-year-old male patient with a 16-year history of HIV infection, who deliberately withdrew the Highly Active Antiretroviral Therapy (HAART) regimen and was hospitalized because of a respiratory infection. Because of a long-term complaint of dyspepsia, an upper gastrointestinal endoscopy was performed disclosing a large elevated and ulcerated gastric lesion, which biopsy revealed a diffuse large B-cell lymphoma. Clinical, imaging and laboratory tests showed an early stage diagnosis: Lugano stage I. Although not frequent, the authors alert to considering this neoplasia in all HIV-positive patients with dyspeptic symptoms.

Introduction: People living with human immunodeficiency virus (PLWH) still face high morbidity and mortality resulting from lymphoma., Aim: To describe a population of PLWH and lymphoma in a Chilean public hospital and compare the overall survival (OS) with a previously reported cohort from the same institution., Methods: Retrospective single-center cohort study. All the patients diagnosed between 2010 and 2017 were included. Demographic and clinical variables were obtained from medical records. The overall survival (OS) was estimated in treated patients from diagnosis until death or October 2020. The OS was then compared with a cohort of patients diagnosed between 1992 and 2008., Main Results: Eighty-four patients were included. The most common histological types were Burkitt´s lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), Hodgkin´s lymphoma (HL) and plasmablastic lymphoma (PBL) at 31%, 27%, 21% and 14%, respectively. The three-year OS for the whole cohort of BL, DLBCL, HL and PBL was 58.9%, 65.2%, 47.4%, 76.4% and 50%, respectively. Compared to the cohort of 1992 to 2008, a global increase in the OS was found after excluding HL and adjusting for age and clinical stage (HR 0.38, p = 0.002). However, when the main types were analyzed individually, the increase in the OS was statistically significant only in DLBCL (HR 0.29, p = 0.007). Most patients with DLBCL received CHOP chemotherapy, as in the previous cohort., Conclusion: The OS has improved in this population, despite no major changes in chemotherapy regimens, mainly due to the universal access to antiretroviral therapy., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Patients with lymphoma can develop cardiac involvement that includes malignant pericardial effusions and myocardial infiltration, but extensive myocardial invasion by tumor with resultant rupture has been reported only rarely. We report a case of a patient with human immunodeficiency virus and T-cell lymphoma who presented with signs and symptoms that were suggestive of a non-ST-elevation myocardial infarction. Plans were made for cardiac catheterization, but the patient developed thrombocytopenia after the initiation of heparin and eptifibatide. Cardiac catheterization was deferred, and shortly afterwards he had a witnessed cardiac arrest in the hospital and could not be resuscitated. Autopsy revealed transmural infiltration of the myocardium with lymphoma and resultant rupture of the left ventricular free wall. To our knowledge, this is the 1st reported case of left ventricular free-wall rupture due to transmural infiltration by human-immunodeficiency-virus--associated peripheral T-cell lymphoma. We conclude that noncoronary causes of chest pain, including direct myocardial infiltration, should be considered in immunocompromised patients with lymphoma. [ABSTRACT FROM AUTHOR]

Pneumocystis species are ascomycetous fungi that obligatorily dwell with no apparent ill effect in the lungs of normal mammals, but they become pathogenic when host defenses are compromised. Identified more than 100 years ago, these atypical fungi manifest characteristics that are unique within the Fungi, such as the lack of ergosterol, genetic complexity of surface antigens, and antigenic variation. Thought to be confined to the severely immunocompromised host, Pneumocystis spp. are being associated with new population niches owing to the advent of immunomodulatory therapies and increased numbers of patients suffering from chronic diseases. The inability to grow Pneumocystis spp. outside the mammalian lung has thwarted progress toward understanding their basic biology, but via the use of new genetic tools and other strategies, researchers are beginning to uncover their biological and genetic characteristics including a biphasic life cycle, significant metabolic capacities, and modulation of lifestyles. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the complete remission (CR) and survival of patients with systematic AIDS-related non-Hodgkin lymphoma (ARL) who are receiving highly active antiretroviral therapy (HAART). Analysis was made on the Grupo de Estudio del SIDA register of systematic ARL to collect cases diagnosed at 15 institutions with active follow-up every 6 months. Results showed that CR was associated with tumor-related factors in patients with ARL and treated with HAART.

To identify cancers that occur at higher rates in acquired immunodeficiency syndrome (AIDS) patients, the cancer experience of New York State (NYS) AIDS patients aged 15–69 years who were diagnosed between 1981 and 1994 was compared with that of the NYS general population. Sex and HIV risk group-specific standardized incidence ratios (SIRs), post-AIDS relative risks, and trends of relative risks were calculated to determine cancer risk. Among non-AIDS-related cancers, elevated SIRs were found for Hodgkin's disease (male, 8.0; female, 6.4; heterosexually infected males, 31.3); cancer of the rectum, rectosigmoid, and anus (male, 3.3; female, 3.0); trachea, bronchus, and lung (male, 3.3; female, 7.5); and brain and central nervous system (male, 3.1; female, 3.4; heterosexually infected females, 23.8) cancers. Moreover, significant trends of increasing relative risks from the pre-AIDS to the post-AIDS period were found for cancers of the rectum, rectosigmoid, and anus; trachea, bronchus, and lung; skin; and connective tissues (all sites, p < 0.05) among males. For AIDS-related cancers in women, invasive cervical cancer had an overall SIR of 9.1 (95% confidence interval: 6.9, 10.8) and a post-AIDS relative risk of 6.5 (95% confidence interval: 4.1, 9.7). This population-based registry linkage analysis evaluates cancer risk in AIDS patients by sex and risk factors and adds evidence that HIV-associated immunosuppression increases the risks of specific types of cancer. [ABSTRACT FROM PUBLISHER]

Background: A 39-year-old patient took medical advice because of progressive fatigue, with nausea, fever, non specific abdominal pain, 3 weeks after coming back from Asia. He had been positive for HIV for 6 years. Blood tests show an increased CRP level (4 mg/dl, nl < 1 mg/dl).