AIDS-defining Cancers Research Articles

Cancer Incidence and Cancer Screening Practices Among a Cohort of Persons Receiving HIV Care in Washington, DC.

In this era of effective combination antiretroviral therapy the incidence of AIDS defining cancers (ADCs) is projected to decline while the incidence of certain non-AIDS defining cancers (NADCs) increases. Some of these NADCs are potentially preventable with appropriate cancer screening. We examined cancer incidence, screening eligibility, and receipt of screening among persons actively enrolled in the DC Cohort, a longitudinal observational cohort of PLWH, between 2011 and 2017. Cancer screening eligibility was determined based on age, sex, smoking history and co-morbidity data available and published national guidelines. The incidence rate of NADCs was 12.1 (95% CI 10.7, 13.8) and ADCs 1.6 (95% CI 0.6, 4.6) per 1000 person-years. The most common incident NADCs were breast 2.6 (95% CI 0.5,1 2.1), prostate 2.3 (95% CI 1.2, 4.3), and non-melanoma skin 1.2 (95% CI 0.6, 2.3) incident diagnoses/cases per 1000 person-years. Among cohort sites where receipt of cancer screening was assessed, less than 60% of eligible participants had any ascertained anal HPV, breast, cervical, colorectal, hepatocellular carcinoma, or lung cancer screening. In this cohort of PLWH, there were more incident NADCs versus ADCs in contrast to earlier cohort studies where ADCs predominated. Despite a large eligible population there were low rates of screening. Implementation of cancer screening is an important component of care among PLWH.

Differences in survival according to malignancy type and degree of immunodeficiency in HIV-infected patients

Background and objectiveAfter the introduction of antiretroviral therapy, a decrease in AIDS defining cancers (ADCs) is observed, while non-AIDS-defining cancers (NADCs) have increased in HIV-infected patients (HIP). We have little information about the prognosis and associated risk factors. We studied survival and its relationship with immunodeficiency after the diagnosis of ADC or NADC. MethodsObservational, retrospective study of 788 HIP of whom 133 developed a malignancy between 2000–2016. Malignancies were divided into ADCs or NADCs and degree of immunodeficiency according to the CD4 T lymphocyte count > or </=200mm–3. Survival was estimated according to the Kaplan Meier method, multivariate COX regression analysis and compared with the log-rank test. Results149 malignancies were diagnosed in 133 HIP: 41.4% ADCs and 58.6 NADCs. The most frequent tumour was NHL (21.1%), followed by lung carcinoma (15%). HCV was positive in 50.4% and 65.4% were smokers. Thirty-nine point one percent had a CD4 T lymphocyte count </=200/mm3, being 60% in the case of ADCs while in NADCs it was 38.5%. CD4 T lymphocyte count </=200mm–3 is significantly associated with lower survival after diagnosis of ADCs(p=0.031) and NADCs (p=0.005). ConclusionsThe most frequent types of tumours in HIP differ from those in the general population, probably due to oncogenic risk factors. CD4 T lymphocyte count </=200mm–3 is a risk factor related to worse prognosis after NADC or ADC diagnosis.

Prevalence and predictors of HIV screening in invasive cervical cancer: a 10 year cohort study

BackgroundInvasive cervical carcinoma is associated with a human immunodeficiency virus (HIV) prevalence of >0.1%, and screening is recommended and cost-effective for cancer populations exceeding this threshold. HIV status is also...

Prevalence and mortality of cancer among people living with HIV and AIDS patients: a large cohort study in Turkey.

Cancer is responsible for elevated human immunodeficiency virus (HIV)-related mortality but there are insufficient data about cancer in HIV-positive patients in Turkey. We aimed to investigate the prevalence and mortality of cancer among people living with HIVand AIDS patients in Istanbul, Turkey. Between January 1998 and December 2016, people living with HIVand AIDS patients were enrolled in this study by the ACTHIV-IST Study Group, which consists of 5 centres to follow-up HIV-positive patients in Istanbul. The cancer diagnoses included AIDS-defining cancers (ADCs) and non AIDS-defining cancers (NADCs). Among 1872 patients, 37 (1.9%) were diagnosed with concurrent cancer. Eleven patients were diagnosed during follow-up; the prevalence of cancer among people living with HIVand AIDS patients was 2.6%. Among 48 cancer patients, 35 patients had ADCs, and 32 of them were diagnosed at their first hospital admission. There were 1007 late presenters and 39 of them had cancer (29 were ADCs). The most prevalent NADCs were gastrointestinal, genitourinary, and pulmonary cancers. NADCs were mostly diagnosed during follow-up of patients. The mortality of this group was significantly higher than that of patients with ADCs (53.9% vs 22.9%). These results indicate the importance of cancer screening at diagnosis and during follow-up of HIV infection. A detailed physical examination contributes to diagnosis of the most prevalent ADCs (Kaposi's sarcoma and non-Hodgkin's lymphoma), especially in late presenters. For NADCs, individual risk factors should be considered.

Cancer spectrum in HIV-infected patients: A zonal hospital experience in Tanzania

Although the burden of human immunodeficiency virus (HIV) infection in Tanzania is high, limited data are available on cancers in HIV-infected patients. We aimed to determine the spectrum and prevalence of cancers in HIV-infected patients attending care at a zonal hospital in Tanzania. Clinical records of HIV-infected patients from 2009 to 2019 were identified and retrospectively reviewed. A total of 3398 HIV-infected patients were recruited with median age of 37 years. Cancer was diagnosed in 9% of the patients after enrollment into HIV clinical care, with an increasing prevalence from 7.2% between years 2009 and 2013 to 8.6% between years 2017 and 2019 (p-value <0.0001). Majority (89.2%) were on antiretroviral therapy (ART) during the time of cancer diagnosis. The proportions of acquired immunodeficiency syndrome (AIDS)-defining cancers and non-AIDS defining cancers were 28% and 72% respectively. Kaposi's sarcoma was the most common (13.2%) AIDS-defining cancer while esophageal cancer was the most common (11.1%) non-AIDS defining cancer. The median duration of time from HIV infection to cancer diagnosis was 715 days (IQR: 98-2570). The median CD4+T-cell count was 318(IQR 159-690) cells/µl at the time of cancer diagnosis and 40.7% of the patients had advanced immunosuppression with CD4 count less than 200 cells/µl at the time of cancer diagnosis. Non-AIDS defining cancers were much more common than AIDS-defining cancers suggesting increased longevity due to ART access. The prevalence of cancer among HIV-infected patients was 9% with an increasing trend over time; highlighting the importance of promoting cancer screening in this vulnerable population and implementation of vaccinations programs for liver and cervical cancers as well as tobacco control policies for smoking-related cancers.

PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.

Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.

Characteristics of Immune Checkpoint Inhibitors Trials Associated With Inclusion of Patients With HIV

Since antiretroviral therapy became widely available in the late 1990s, there has been a dramatic reduction in AIDS-related deaths due to opportunistic infections.1 The life expectancy of people living with HIV (PLWH) receiving antiretroviral therapy now approaches that of the general population, particularly for those with a CD4+ T-cell count within the normal range.2 Conversely, cancer has become a leading cause of morbidity and mortality in PLWH. From 1995 to 2009, cancer resulted in nearly two-fold as many deaths per 100 000 person-years in PLWH than in the general population (327 deaths per 100 000 person-years vs 186 deaths per 100 000 person-years).3 Non–AIDS-defining cancers represent 70% of these deaths and will increase with aging of the PLWH population.3 During the past decade, clinical trials of immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many cancers. Historically, PLWH have been excluded from participation in oncology trials, which may affect generalizability of findings. In this systematic review and meta-analysis, we investigated characteristics of ICI trials associated with inclusion of PLWH.

Diferencias en supervivencia según el tipo de cáncer y el grado de inmunodeficiencia en pacientes con infección VIH

Background and objectiveAfter the introduction of antiretroviral therapy, a decrease in AIDS defining cancers (ADCs) is observed, while non-AIDS-defining cancers (NADCs) have increased in HIV-infected patients (HIP). We have little information about the prognosis and associated risk factors. We studied survival and its relationship with immunodeficiency after the diagnosis of ADC or NADC. Material and methodsObservational, retrospective study of 788 HIP of whom 133 developed a malignancy between 2000-2016. Malignancies were divided into ADCs or NADCs and degree of immunodeficiency according to the CD4 T lymphocyte count> or </=200/mm3. Survival was estimated according to the Kaplan Meier method, multivariate COX regression analysis and compared with the log-rank test. Results149 malignancies were diagnosed in 133 HIP: 41.4% ADCs and 58.6 NADCs. The most frequent tumour was NHL (21.1%), followed by lung carcinoma (15%). HCV was positive in 50.4% and 65.4% were smokers. Thirty-nine point one percent had a CD4 T lymphocyte count </=200/mm3, being 60% in the case of ADCs while in NADCs it was 38.5%. CD4 T lymphocyte count </=200/mm3 is significantly associated with lower survival after diagnosis of ADCs(p=.031) and NADCs (p=.005). ConclusionsThe most frequent types of tumours in HIP differ from those in the general population, probably due to oncogenic risk factors. CD4 T lymphocyte count </=200/mm3 is a risk factor related to worse prognosis after NADC or ADC diagnosis.

HIV associated cancers.

e18254 Background: The incidence or the prevalence of AIDS-defining cancers has reduced drastically (70% or more in the United States) since the introduction of three-drug antiretroviral therapy (ART) in the mid-1990s. However, the data from the inpatient sample is lacking. Methods: This is a retrospective analysis using data from the 2014 National Inpatient Sample database. We identified patients with either primary or secondary diagnosis of human immunodeficiency virus (HIV). Then we identified patients with various cancers including AIDS-defining cancers. Afterward, we ran logistic regression to check the degree of association between the diagnosis of each cancer with the diagnosis of HIV during the identified hospitalizations. We also assessed the prevalence of each of the cancer among the identified HIV patients, as well as the mortality in this cohort. Results: A total of 115955 hospitalizations with a diagnosis of HIV were identified. Among them, there were 6985 hospitalizations with Non-Hodgkin lymphoma, 2230 with rectal and anal cancer, 1170 with Kaposi sarcoma, 870 with head and neck cancer, 865 with skin cancer, 840 with cervical cancer. Logistic regression showed odds ratio (OR) of 1632.857 (95% CI 1168 - 2284, p &lt; 0.01) for Kaposi sarcoma, 9.13 (95% CI 5.7-14.5, p-value &lt; 0.01) for other male cancer, 8.34 (95% CI 7.68-9.06; p-value &lt; 0.01) for Non-Hodgkin's lymphoma, 6.65 (95% CI was 5.5-8, p-value &lt; 0.01) for Hodgkin's lymphoma, 5.04 (95% CI 4.5-5.6 p &lt; 0.01) for rectal and anal cancer, 2.33 (95% CI 1.9-2.8, p &lt; 0.01) for cervical cancer. Mortality was statistically significant with liver cancer, lung cancer, brain cancer, Hodgkin lymphoma, and Kaposi sarcoma. Conclusions: The prevalence of Kaposi sarcoma, Non-Hodgkin lymphoma, and cervical cancer are found to be high among hospitalized patients with HIV most likely because of nonadherence to their HIV medications. Future studies to check their correlation of these cancers with disease control is required. It is interesting to note that the prevalence of rectal and anal cancer, head and neck cancer, and skin cancer is high in this cohort.

Risk of cancer in HIV-infected patients in Spain, 2004–2015. The CoRIS cohort study

IntroductionCancer is a leading cause of death in individuals with HIV. MethodsThe incidence of cancer in HIV patients of the CoRIS cohort in the 2004–2009 and 2010–2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. ResultsBetween January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51–781.42) with no significant differences between the 2 periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010–2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21–0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13–14.17; females: 21.83, 2.66–47.79), non-Hodgkin's lymphoma in males (5.30, 2.86–8.45) and cervical cancer (7.43, 3.15–13.87) and head and neck cancer (3.28, 1.21–5.82) in women. ConclusionsThe overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients.

The burden of cancers associated with HIV in the South African public health sector, 2004\u20132014: a record linkage study

IntroductionThe impact of South Africa’s high human immunodeficiency virus (HIV) burden on cancer risk is not fully understood, particularly in the context of antiretroviral treatment (ART) availability. We examined national cancer trends and excess cancer risk in people living with HIV (PLHIV) compared to those who are HIV-negative.MethodsWe used probabilistic record linkage to match cancer records provided by the National Cancer Registry to HIV data provided by the National Health Laboratory Service (NHLS). We also used text search of specific HIV terms from the clinical section of pathology reports to determine HIV status of cancer patients. We used logistic and Joinpoint regression models to evaluate the risk and trends in cancers in PLHIV compared to HIV-negative patients from 2004 to 2014. In sensitivity analysis, we used inverse probability weighting (IPW) to correct for possible selection bias.ResultsA total of 329,208 cancer cases from public sector laboratories were reported to the NCR from 2004 to 2014 with the HIV status known for 95,279 (28.9%) cancer cases. About 50% of all the female cancer cases (n = 30,486) with a known status were HIV-positive. PLHIV were at higher risk of AIDS-defining cancers (Kaposi sarcoma [adjusted OR:134, 95% CI:111–162], non-Hodgkin lymphoma [adjusted OR:2.73, 95% CI:2.56–2.91] and, cervix [adjusted OR:1.70, 95% CI:1.63–1.77], conjunctival cancer [adjusted OR:21.5, 95% CI:16.3–28.4] and human papilloma virus (HPV) related cancers (including; penis [adjusted OR:2.35, 95% CI:1.85–2.99], and vulva [adjusted OR:1.94, 95% CI:1.67–2.25]) compared to HIV-negative patients. Analysis using the IPW population yielded comparable results.ConclusionThere is need for improved awareness and screening of conjunctival cancer and HPV-associated cancers at HIV care centres. Further research and discussion is warranted on inclusive HPV vaccination in PLHIV.

The Changing Face of HIV-Associated Malignancies: Advances, Opportunities, and Future Directions.

Because of tremendous advances in HIV care, the survival of many people living with HIV (PLWH) now approaches that of the general population. This has led to a shift in the types of malignancies diagnosed among PLWH from AIDS-defining cancers during the height of the HIV epidemic toward more non-AIDS-defining cancers and age-related incidental cancers in the last 2 decades. Despite these trends, positive cancer outcomes still lag behind patients without HIV, and many PLWH never receive appropriate cancer therapy. We explore the reasons for the epidemiologic shift that has been observed, as well as the factors that influence treatment disparities. Furthermore, several studies have demonstrated similar cancer survival rates when PLWH and certain cancers receive the same treatment as those who are HIV-negative. Among possible solutions to improve cancer outcomes include increasing the inclusion of PLWH in clinical trials, using guidelines specific for the treatment of HIV-associated malignancies, and incorporating a multidisciplinary approach to cancer management in PLWH.

Reduction of Kaposi's Sarcoma-Associated Herpesvirus Latency Using CRISPR-Cas9 To Edit the Latency-Associated Nuclear Antigen Gene.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), an AIDS-defining cancer in HIV-1-infected individuals or immune-suppressed transplant patients. The prevalence for both KSHV and KS are highest in sub-Saharan Africa where HIV-1 infection is also epidemic. There is no effective treatment for advanced KS; therefore, the survival rate is low. Similar to other herpesviruses, KSHV's ability to establish latent infection in the host presents a major challenge to KS treatment or prevention. Strategies to reduce KSHV episomal persistence in latently infected cells might lead to approaches to prevent KS development. The CRISPR-Cas9 system is a gene editing technique that has been used to specifically manipulate the HIV-1 genome but also Epstein-Barr virus (EBV) which, similar to KSHV, belongs to the Gammaherpesvirus family. Among KSHV gene products, the latency-associated nuclear antigen (LANA) is absolutely required in the maintenance, replication, and segregation of KSHV episomes during mitosis, which makes LANA an ideal target for CRISPR-Cas9 editing. In this study, we designed a replication-incompetent adenovirus type 5 to deliver a LANA-specific Cas9 system (Ad-CC9-LANA) into various KSHV latent target cells. We showed that KSHV latently infected epithelial and endothelial cells transduced with Ad-CC9-LANA underwent significant reductions in the KSHV episome burden, LANA RNA and protein expression over time, but this effect is less profound in BC3 cells due to the low infection efficiency of adenovirus type 5 for B cells. The use of an adenovirus vector might confer potential in vivo applications of LANA-specific Cas9 against KSHV infection and KS.IMPORTANCE The ability for Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma (KS), to establish and maintain latency has been a major challenge to clearing infection and preventing KS development. This is the first study to demonstrate the feasibility of using a KSHV LANA-targeted CRISPR-Cas9 and adenoviral delivery system to disrupt KSHV latency in infected epithelial and endothelial cell lines. Our system significantly reduced the KSHV episomal burden over time. Given the safety record of adenovirus as vaccine or delivery vectors, this approach to limit KSHV latency may also represent a viable strategy against other tumorigenic viruses and may have potential benefits in developing countries where the viral cancer burden is high.

AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Riesgo de cáncer en personas con VIH en España, 2004-2015. Estudio de la cohorte CoRIS

IntroductionCancer is a leading cause of death in individuals with HIV. MethodsThe incidence of cancer in HIV patients of the CoRIS cohort in the 2004-2009 and 2010-2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. ResultsBetween January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51-781.42) with no significant differences between the 2periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010-2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21-0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13-14.17; females: 21.83, 2.66-47.79), non-Hodgkin's lymphoma in males (5.30, 2.86-8.45) and cervical cancer (7.43, 3.15-13.87) and head and neck cancer (3.28, 1.21-5.82) in women. ConclusionsThe overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients.

Editorial Commentary: Challenge of Non–AIDS-Defining Cancers (NADCs), Focusing on Trans Activation Response Element (TAR) RNA Embedding Exosomes

Editorial Commentary: Challenge of Non–AIDS-Defining Cancers (NADCs), Focusing on Trans Activation Response Element (TAR) RNA Embedding Exosomes

As the HIV-positive population ages, new dangers loom: Researchers are exploring human immunodeficiency virus-mediated inflammation and immune dysregulation to better understand the higher risks of cancer, cardiovascular disease, and other conditions among individuals who carry the virus.

As the HIV-positive population ages, new dangers loom: Researchers are exploring human immunodeficiency virus-mediated inflammation and immune dysregulation to better understand the higher risks of cancer, cardiovascular disease, and other conditions among individuals who carry the virus.

The impact of HIV infection on the development of cutaneous cancers

Human immunodeficiency virus (HIV) infection continues to be an important public health issue. Immunosuppression is responsible for the development of much comorbidity among HIV-infected patients. Of these, malignancies play an important role in the prognosis of the disease. Cancers diagnosed in HIV-infected patients can be divided into two main categories: AIDS-defining cancers and non-AIDS-defining cancers. In the second category, skin cancers represent an important subgroup, the most common being basal cell carcinoma, squamous cell carcinoma and melanoma.

Radiation-Sparing Treatment of HIV-Related Primary Central Nervous System Lymphoma with Antiretroviral Therapy, Rituximab and High-Dose Methotrexate

BACKGROUND: HIV-associated primary central nervous system lymphoma (HIV-PCNSL) is an AIDS-defining cancer. Tumors occur in patients with very low CD4+ counts, and tumors are almost always Epstein-Barr virus (EBV) infected. Overall survival (OS) has improved over time with antiretroviral therapy (ART)-associated immune reconstitution but is still generally less than 1 year. Treatment has traditionally included whole brain radiation, which can lead to devastating long-term neurotoxicity, including cognitive decline. ART has made it possible to treat patients with curative-intent, but radiation-sparing approaches have not been studied prospectively in HIV-PCNSL.METHODS: In a prospective phase II pilot study conducted in the HIV & AIDS Malignancy Branch at the National Cancer Institute, we evaluated curative-intent radiation-sparing immunochemotherapy in patients with untreated HIV-PCNSL (NCT00267865). Patients with HIV-PCNSL received ART, rituximab (375 mg/m2) and HD-MTX (6 g/m2) with leucovorin rescue (R-HD-MTX). Responses were evaluated by modified International Working Group Response Criteria for PCNSL after 6 cycles of induction R-HD-MTX and patients with a complete response (CR) received 2 consolidation cycles of R-HD-MTX. Patients with poor renal or cardiac function who were not eligible to receive HD-MTX at enrollment, received ART, rituximab and best-available radiation-sparing care. The primary objective of the study was to estimate the percentage of patients receiving ART and R-HD-MTX alive without recurrent lymphoma at two years. Response to treatment, immune reconstitution, and OS were evaluated using descriptive statistics and Kaplan-Meier methodology.RESULTS: Twelve patients were enrolled between September 2006 and June 2016. One enrolled patient was initially ineligible to receive HD-MTX due to renal dysfunction and received rituximab with temozolomide (TMZ) 150 mg/m2 for 5 days for one cycle followed by 6 cycles of R-HD-MTX + TMZ and 2 consolidation cycles of R-HD-MTX. Patient characteristics: 9 men, 3 women; median (med) age 33 years (range: 21-55); 8 African-American, 3 Hispanic, 1 white non-Hispanic; med Eastern Cooperative Oncology Group performance status 2 (1-3); med baseline Mini Mental State Examination (MMSE, maximum score = 30) was 22 (range: 5-29). Only 4 patients were on ART prior to diagnosis, and all but 1 had been on ART less than 4 months. Med time from HIV infection to PCNSL diagnosis was 30 weeks (range: 0-23 years). Med CD4+ T-cell count at PCNSL diagnosis was 16 cells/µL (0-409). Diagnosis of PCNSL was biopsy-confirmed (11) or made by 18fludeoxyglucose positron emission tomography/cerebral spinal fluid (CSF) EBV viral load criteria (1). 11/12 tumors were EBV positive. Flow cytometry showed leptomeningeal disease in 4 patients. Three had concurrent CNS infections, including Cryptococcus, histoplasmosis, and CMV retinitis. Ten were evaluable for response to R-HD-MTX induction. Two patients received only 1 cycle of therapy and were not evaluable due to treatment failure (TF). Responses after R-HD-MTX induction: CR (5), partial response (PR) (4) and progressive disease (PD) (1). Two patients with a PR received second-line TMZ at end of R-HD-MTX and obtained a subsequent CR. The patient with PD received second-line therapy with the Cancer and Leukemia Group B 50202 induction regimen and obtained a subsequent CR. There were 4 deaths on study: 1 pulmonary embolism, 1 CNS fungal infection in setting of PD, 2 TF. Eight patients (67%), including 3 patients who received second line therapy, obtained a durable CR. Med CD4+ T-cell increase following R-HD-MTX induction was +35 cells/uL (range: -54 - +369). In surviving patients, med MMSE after R-HD-MTX was 28 (27-30). For all patients, estimated 60-month OS was 66% (95% CI: 32-86%) with med potential follow-up of 82 months. Med OS was not reached. CONCLUSIONSTreatment with ART and R-HD-MTX is associated with a high response rate, CD4+ immune reconstitution, preserved cognition, and improved OS, even in a high-risk patient population. DisclosuresUldrick:Celgene: Patents & Royalties: 10,001,483 B2; Celgene: Research Funding; Merck: Research Funding. Yarchoan:NIH: Patents & Royalties: Patents on IL-12 for KS and cereblon-binding drugs for KSHV diseases. Spouse has patent on KSHV IL-6. Patents assigned to DHHS/NIH.; Celgene Corp.: Research Funding.

High Cancer Burden Among Antiretroviral Therapy Users in Malawi: A Record Linkage Study of Observational Human Immunodeficiency Virus Cohorts and Cancer Registry Data.

With antiretroviral therapy (ART), AIDS-defining cancer incidence has declined and non-AIDS-defining cancers (NADCs) are now more frequent among human immunodeficiency virus (HIV)-infected populations in high-income countries. In sub-Saharan Africa, limited epidemiological data describe cancer burden among ART users. We used probabilistic algorithms to link cases from the population-based cancer registry with electronic medical records supporting ART delivery in Malawi's 2 largest HIV cohorts from 2000-2010. Age-adjusted cancer incidence rates (IRs) and 95% confidence intervals were estimated by cancer site, early vs late incidence periods (4-24 and >24 months after ART start), and World Health Organization (WHO) stage among naive ART initiators enrolled for at least 90 days. We identified 4346 cancers among 28 576 persons. Most people initiated ART at advanced WHO stages 3 or 4 (60%); 12% of patients had prevalent malignancies at ART initiation, which were predominantly AIDS-defining eligibility criteria for initiating ART. Kaposi sarcoma (KS) had the highest IR (634.7 per 100 000 person-years) followed by cervical cancer (36.6). KS incidence was highest during the early period 4-24 months after ART initiation. NADCs accounted for 6% of new cancers. Under historical ART guidelines, NADCs were observed at low rates and were eclipsed by high KS and cervical cancer burden. Cancer burden among Malawian ART users does not yet mirror that in high-income countries. Integrated cancer screening and management in HIV clinics, especially for KS and cervical cancer, remain important priorities in the current Malawi context.