HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.

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.

Hematologic cancers in individuals infected by HIV.

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.

Oral Plasmablastic Lymphoma: A Rare Manifestation of HIV-Related Neoplasm-A Brief Clinical Study.

Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency virus-positive patients. Though the oral cavity is a common site for PBL, this condition is not commonly reported in the literature as an oral manifestation. Most oral PBLs presented as an asymptomatic swelling, frequently associated with ulcerations and bleeding. No standard treatment is yet advocated for oral PBL. Five-year survival rate was recorded not more than 33.5%. This presentation emphasizes on oral manifestation of plasmablastic lymphoma (PBL) as a rare entity, which was provisionally diagnosed for carcinoma (CA) oral cavity. A simple presentation of ulcerated growth in the upper jaw was excised for histopathologic evaluation. Subsequently, it turned out to be a rare oral manifestation of HIV-related lymphoma. It is imperative to understand simple oral presentation as a manifestation of an underlying systemic condition. With this interest, this case presentation is published with a literature review.

Human Immunodeficiency Virus Associated Plasmablastic Lymphoma Involving Bones and Peritoneum in a 4-Year-old Child.

In children with underlying Human Immunodeficiency virus infection and AIDS, hematolymphoid cancers, especially non-hodgkin lymphomas are common. Plasmablastic lymphoma is one such non-hodgkin lymphomas arising from the head and neck region (especially sinonasal) but extremely rare. We describe the clinical course in a 4-year-old boy who presented with a solitary bony swelling of the right knee joint, which on diagnostic work-up turned out to be plasmablastic lymphoma. With combination chemotherapy, intrathecal chemotherapy, and early institution ofHighly active anti-retroviral therapy, the child continues to be in remission.

HIV-related lymphomas.

PURPOSE OF REVIEW: To summarize the recent evidence on the pathology, current standard of care and recent advances in the treatment of HIV-related lymphomas. RECENT FINDINGS: Lymphomas remain a major cause of morbidity and mortality in people living with HIV, even in the era of combination antiretroviral therapy (cART). However, treatment outcomes for these malignancies have improved in recent decades, due to full-dose chemotherapy, effective cART and supportive care. Recent advances include the identification of novel driving signaling pathways as promising molecular targets to improve lymphoma outcomes. SUMMARY: Patients with HIV-related lymphomas who receive effective cART should be treated like the general population.

Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial).

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.

Clinical observations of bone marrow transfusion for promoting bone marrow reconstruction after chemotherapy for AIDS-related lymphoma.

BACKGROUND: This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). METHODS: A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. RESULTS: Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. CONCLUSIONS: Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.

Optimizing treatment of HIV-associated lymphoma.

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.

Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma.

Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.

Long-term remission of AIDS-related primary central nervous system lymphoma in a patient under antiretroviral therapy: a case report and review of the literature.

BACKGROUND: AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/µl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2-3 months if left untreated. CASE DESCRIPTION: A 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT. CONCLUSION: Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.

Incidence and spectrum of infections among HIV/AIDS patients with lymphoma during chemotherapy.

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.

Mexican consensus on Hodgkin's lymphoma.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.Hodgkin's lymphoma (HL) is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. HL is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Cause-specific mortality after diagnosis of cancer among HIV-positive patients: A collaborative analysis of cohort studies.

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.

Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice.

The MATRix chemoimmunotherapy regimen is highly effective in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). However, nothing is known about its feasibility and efficacy in everyday practice, where patients are more often older/frailer than those enrolled in clinical trials. We conducted a retrospective study addressing tolerability/efficacy of MATRix in 156 consecutive patients with newly diagnosed PCNSL treated outside a clinical trial. Median age and ECOG Performance Status of considered patients were 62 years (range 28-78) and 2 (range 0-4). The overall response rate after MATRix was 79%. Nine (6%) treatment-related deaths were recorded. After a median follow-up of 27.4 months (95% confidence interval [CI] 24.4-31.9%), the two-year progression-free and overall survival were 56% (95% CI 48.4-64.9%) and 64.1% (95% CI 56.7-72.5%) respectively. Patients not eligible for the IELSG32 trial were treated with lower dose intensity and had substantially worse outcomes than those fulfilling inclusion criteria. This is the largest series of PCNSL patients treated with MATRix outside a trial and recapitulates the IELSG32 trial outcomes in the non-trial setting for patients who fit the trial criteria. These data underscore the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.

Chronic medical conditions and late effects following non-Hodgkin lymphoma in HIV-uninfected and HIV-infected adolescents and young adults: a population-based study.

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.

Plasma Epstein-Barr Virus Load as an Early Biomarker and Prognostic Factor of Human Immunodeficiency Virus-related Lymphomas.

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.

Plasmablastic lymphoma achieving sustained remission with antiretroviral therapy alone.

Despite advances in the treatment of most human immunodeficiency virus (HIV)-related lymphomas, the outcomes for patients with HIV-related plasmablastic lymphoma (PBL) remain poor. While studies have shown an increased survival for patients with most kinds of HIV-related lymphomas since the introduction of highly active antiretroviral therapy (HAART), the impact of HAART on survival in patients with HIV-related PBL is unclear, mainly because the condition is rare and the number of published studies is small. Few case reports have shown regression of PBL after initiation of HAART, however, usually followed by recurrence of PBL or achieved with a need for chemotherapy. We report the first case of PBL in a 38-year-old man with newly diagnosed HIV who achieved sustained remission after the initiation of HAART alone and who remains in remission seven years after diagnosis, without a need for chemotherapy or radiation. We illustrate the importance of initiating HAART therapy under the supervision of infectious disease specialists as soon as the PBL is diagnosed until future studies provide clear evidence in the management of HIV-related PBL.

Molecular Biology of EBV in Relationship to HIV/AIDS-Associated Oncogenesis.

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.

A case-control study of HIV infection and cancer in the era of antiretroviral therapy in Rwanda.

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.

The role of brain biopsy in the clinical management of HIV-related focal brain lesions.

OBJECTIVES: Up to 20% of HIV-related focal brain lesion (FBL) diagnoses cannot be determined without invasive procedures. In such cases, brain biopsy is an important step in the evaluation algorithm. The aims of this study were to describe the clinical outcomes of patients with FBL, the proportion of diagnoses confirmed by brain biopsies and their aetiologies, and to analyse the proportion of patients in whom the biopsy motivated a change in therapeutic management. METHODS: A retrospective cohort study was performed. The data from clinical records of patients with HIV-related FBL admitted between January 2005 and December 2015 were reviewed. RESULTS: A total of 137 patients were included in the study. The median age was 39 years [interquartile range (IQR) 33-44.5 years]. The median CD4 count was 54 cells/µL (IQR 21-124 cells/µL). Cerebral brain biopsy was performed in 21.16% of patients (29 of 137); 68.9% of these individuals (20 of 29) were diagnosed by histology, with results of central nervous system (CNS) lymphoma in 20.6% (six of 29), progressive multifocal leucoencephalopathy in 6.8% (two of 29), toxoplasmosis in 6.8% (two of 29), tuberculoma in 6.8% (two of 29), and other diagnoses in 27.6% (eight of 29). In nine patients, the histology was nonspecific. In 75.8% of patients (22 of 29), the result of the biopsy led to a change in the therapeutic management. We did not observe higher rates of mortality related to the procedure. Overall mortality at 30 and 90 days was similar in patients who were and were not biopsied. CONCLUSIONS: In this retrospective cohort study, cerebral biopsy was associated with significant adjustments in therapeutic management for a high percentage of patients.