Barriers to adherence to antiretroviral treatment in a regional hospital in Vredenburg, Western Cape, South Africa

BACKGROUND: South Africa currently runs the largest public antiretroviral treatment (ART) programme in the world, with over 80% of people living with HIV and/or AIDS on ART. However, in order to appreciate the benefits of using ART, patients are subject to uncompromising and long-term commitments of taking at least 95% of their treatment as prescribed. Evidence shows that this level of adherence is seldom achieved because of a multilevel and sometimes interwoven myriad of factors. Objective: We described the challenges faced by patients on ART in Vredenburg with regard to ART adherence. METHODS: A descriptive qualitative research design was used. Eighteen non-adhering patients on ART in the Vredenburg regional hospital were purposefully selected. Using a semistructured interview guide, we conducted in-depth interviews with the study participants in their mother tongue (Afrikaans). The interviews were audio-taped, transcribed verbatim and translated into English. The data were analysed manually using the thematic content analysis method. RESULTS: Stigma, disclosure, unemployment, lack of transport, insufficient feeding, disability grants and alternative forms of therapy were identified as major barriers to adherence, whereas inadequate follow-ups and lack of patient confidentiality came under major criticisms from the patients. CONCLUSION: Interventions to address poverty, stigma, discrimination and disclosure should be integrated with group-based ART adherence models in Vredenburg while further quantitative investigations should be carried out to quantify the extent to which these factors impede adherence in the community.IS

Human immunodeficiency and Hodgkin lymphoma

The original publication is available at http://www.sciencedirect.comPresentation of Hodgkin lymphoma (HL) is distinctive in the infected individual being more advanced, accompanied by B symptoms and the presence of extranodal disease particularly lymphadenopathy of the head and neck. Bone marrow involvement may be found in over 50% of cases. Virtually all co express gamma-herpesvirus. Phenotypically there is prominence of the mixed-cellularity and lymphocyte depleted histopathologic subtypes that define an aggressive clinical course in comparison to other variants. Prior to the induction of cART, median survival was only 1–2 years. Notably the first chemotherapy trial using ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in 21 patients, without treating the viral infection, resulted in a 43% complete remission rate accompanied by severe haematological toxicities but did not extend median survival with this being 1.5 years matching the negative cases. Significant change accompanied concomitant anti-retroviral therapy that could be given safely even with dose intensive regimens exemplified by BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in 12 patients or the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, prednisone) coupled with involved-field radiation for bulky disease studied in 59 patients. BEACOPP extended overall survival (OS) to 83% at 2 years. A similar trend was seen when using the Stanford V regimen with an OS rate of 51% at 3 years, disease- free survival (DFS) of 68% and freedom from progression (FFP) in 60%. Additional benefits accrued from supportive care with stimulatory peptides such as G-CSF and when combined with bacterial prophylaxis results approached that found in the uninfected reference group. Current consensus holds this particular lymphoma as still among the non-AIDS defining cancers being lung, stomach, liver or anal despite these having recently gained more attention as several of these neoplasms may be occurring more commonly in the era of cART. While the relative risk of developing a non-AIDS-defining neoplasm in HIV-infected persons on the average is 2–3 times, the risk for developing HL in HIV-infected cases impressively ranges between 5 and 25 times when compared to the general population. Based on the precedent in which Kaposi sarcoma and the non-Hodgkin lymphomas distinctively alter the course of this retroviral infection in a way indistinguishable from concurrent Hodgkin lymphoma we propose that this entity be similarly regarded and the hypothesis tested in large randomised prospective study.Publishers' Versio

AIDS-related Kaposi's sarcoma: epidemiological, diagnostic, treatment and control aspects in sub-Saharan Africa.

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

Lymphoma : emerging realities in sub-Saharan Africa

The original publication is available at http://www.sciencedirect.comSubstantial geographical differences exist for Hodgkin and other lymphoproliferative disorders with these having previously been documented in a report from the lymphoma reclassification project. In the light of rampant human immunodeficiency syndrome, largely centred in sub-Sahara, this experience is updated in a further 512 consecutive individuals treated over an 8-year period in a privately based academic centre. Median age was 55.2 years 61% were males, 10% had Hodgkin lymphoma and, overall, constitutional symptoms were present in 20%. Prior to referral 19% had received chemotherapy and a further 20% some form of irradiation. Median survival in hairy cell leukaemia (n = 14), chronic lymphocytic leukaemia–small lymphocytic lymphoma (n = 103), Hodgkin (n = 41) and follicular lymphoma (n = 59) was not reached at the time of analysis and exceeded 36 months. This was followed by 32 months for those with mantle cell (n = 7), splenic (n = 2) and extranodal marginal cell (n = 11), 24 months for T-cell lymphomas (n = 24), 20 months for diffuse large B-cell variants (n = 88) but only 12 months for the aggressive tumours exemplified by Burkitt (n = 7) and lymphoblastic subtypes (n = 6). The remaining 36 patients had to be excluded because numbers were too small for statistical analysis or unreliable staging. Adverse factors were constitutional symptoms, prior treatment with chemotherapy, intermediate or high-risk scores as defined by the international prognostic index, histologic grading and certain anatomical sites of primary tumour. In contrast gender, staging by Rye or Rai classification, retroviral infection and prior treatment with radiotherapy were without effect. Overall survival at 3 years in each category was compared to the curve for the entire cohort and was 100% in hairy cell leukaemia receiving two chlorodeoxyadenosine and greater than 88% in Hodgkin lymphoma treated according to the German study group protocols (p = 0.0004). Corresponding figures for chronic lymphocytic leukaemia–small lymphocytic lymphoma were 82% (p = 0.0006), follicular lymphoma 71% (p = 0.060), peripheral T-cell lymphoma 43% (p = 0.0156), diffuse large B-cell lymphoma 39% (p < 0.0001), aggressive tumours 25% (p = 0.0002) and for the indolent categories including mantle cell, splenic and extra nodal marginal cell lymphomas 22% (p = 0.2023). Outcome argues in favour of patient management by a multidisciplinary team implicit in which are standardised protocols for diagnosis, staging and treatment. Under these circumstances the well recognized centre effect applies when results approximate those from first world reference centres. Conversely any deviation from such a disciplined approach is unlikely to achieve comparable benefit and therefore to be strongly discouragedPublishers' Versio

Biomarkers of HIV-associated cancer

CITATION: Flepisi, B.T., et al. 2014. Biomarkers of HIV-associated cancer. Biomarkers in Cancer, 6: 11-20, doi: 10.4137/BIC.S15056.The original publication is available at http://www.la-press.comCancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.http://www.la-press.com/biomarkers-of-hiv-associated-cancer-article-a4282Publisher's versio

Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (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, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. 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 epidemiologic, diagnostic, and therapeutic strategies