Background Long term survival for patients with AIDS-related diffuse large B-cell lymphoma (DLBCL) is feasible in settings with available combination antiretroviral therapy (cART). However, given limited oncology resources, outcomes for AIDS-associated DLBCL in South Africa are unknown. Methods We performed a retrospective analysis of survival in patients with newly diagnosed AIDS-related diffuse large B-cell lymphoma (DLBCL) treated at a tertiary teaching hospital in Cape Town, South Africa with CHOP or CHOP-like chemotherapy (January 2004 until Dec 2010). HIV and lymphoma related prognostic factors were evaluated. Results 36 patients evaluated; median age 37.3 years, 52.8% men, and 61.1% black South Africans. Median CD4 count 184 cells/μl (in 27.8% this was < 100 cells/μl), 80% high-risk according to the age-adjusted International Prognostic Index. Concurrent Mycobacterium tuberculosis in 25%. Two-year overall survival (OS) was 40.5% (median OS 10.5 months, 95%CI 6.5 – 31.8). ECOG performance status of 2 or more (25.4% versus 50.0%, p = 0.01) and poor response to cART (18.0% versus 53.9%, p = 0.03) predicted inferior 2-year OS. No difference in 2-year OS was demonstrated in patients co-infected with Mycobacterium tuberculosis (p = 0.87). Conclusions Two-year OS for patients with AIDS-related DLBCL treated with CHOP like regimens and cART is comparable to that seen in the US and Europe. Important factors effecting OS in AIDS-related DLBCL in South Africa include performance status at presentation and response to cART. Patients with co-morbid Mycobacterium tuberculosis or hepatitis B seropositivity appear to tolerate CHOP in our setting. Additional improvements in outcomes are likely possible.

The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and roll out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish what impact the HIV epidemic and the ARV roll-out treatment program is having on the incidence of HIV related Lymphoma (HRL). Early data documents that despite the ART roll out, cases of HRL are increasing in this geographical location, now comprising 37% of all lymphomas seen in 2009 which is an increase from 5 % in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted, are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B Cell lymphoma subtypes. The reasons for this observed increase in HRL is not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnosis are made, has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reason, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression.

Summary Until the 1980s, little attention had been accorded to endemic Kaposi's sarcoma (KS), a neoplasm noted in several parts of Southern Europe and the African continent but with relatively slow progression, except in children and young adults. Furthermore, therapeutic approaches based on surgery, radiation and topical treatment were of limited efficacy, mostly used to overcome the disabling and stigmatizing effects of the disease. With the emergence of the HIV/AIDS epidemic, and the profound impact of KS on AIDS‐related mortality, the pathogenesis of KS has been better studied, and the realisation that a virus (KS‐associated Herpesvirus or Human Herpesvirus 8, or KSHV/HHV‐8), combined with immunosuppression and cytokine‐induced growth, was responsible for the development of this disease has led to novel therapeutic approaches. These are unfortunately still highly toxic, require careful monitoring, and are expensive, thus limiting their use in most parts of Africa. However, the use of highly active antiretroviral therapy (HAART), which has led to a considerable decline in KS incidence in populations of industrialized countries, constitutes the best hope for the control of this stigmatizing and lethal disease in Africa. Trials comparing different regimens of antiretroviral drugs in combination with systemic chemotherapeutic agents are urgently needed.

Burkitt lymphoma (BL) accounts for the majority of pediatric non-Hodgkin lymphomas being less common but significantly more lethal when diagnosed in adults. Much of our knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes (SMGs) including more genetic features that associate with tumor EBV status, and unraveled new distinct subgroupings within BL and DLBCL with three predominantly comprising BLs: DGG-BL (DDX3X, GNA13 and GNAI2), IC-BL (ID3, CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and non-coding mutations caused by aberrant somatic hypermutation (aSHM). The largest subgroups of BL cases, IC-BL and DGG-BL are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiological, diagnostic, and therapeutic strategies.