Lack of response of anal intra-epithelial neoplasia to highly active antiretroviral therapy.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
Mark Bower
Publications and source records attributed to Mark Bower.
The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors.
A small proportion of patients with human immunodeficiency virus type 1 (HIV-1) remains asymptomatic for a long period after infection. It is thought that a vigorous immune response may contribute to long-term nonprogression, though studies are confounded by heterogeneity among patients. We studied the levels of HIV-1 receptors, costimulatory T-cell molecules, and dendritic cell (DC) numbers in 18 patients with long-term infection, CD4 counts greater than 400 cells/mm(3), and HIV-1 viral loads lower than 50 copies/mL. These patients were further differentiated through the presence or absence of 2-LTR DNA circles, a possible marker for residual ongoing HIV-1 replication. A statistically significant increase in levels of CD91, the heat-shock protein (HSP) receptor, was observed in therapy-naive patients who had no evidence of ongoing viral replication (P =.01). This difference was most notable on their monocytes. High levels of CD91 may be a host factor that contributes to the maintenance of long-term nonprogression. The ability of CD91 to internalize alpha-defensins and to cross-present exogenous antigen to cytotoxic T lymphocytes through major histocompatibility complex (MHC) class 1 may maintain CD8(+) responses in these patients.
Antigens, CD↗
What can oncologists learn from HIV?
Developments in HIV-related medicine have significant implications for the practice of oncology. Although HIV is a relatively new discipline within medicine, the identification and therapeutic targeting of HIV has been rapid. Furthermore, political lobbying has sculpted scientific research and patient care. Rational drug design has reduced morbidity and mortality to such an extent that the development of predictive surrogate endpoints has been necessary to enable randomised assessments of new protocols to continue. These studies now include the routine detection of resistance to tailor specific therapies to the patient. The involvement of affected communities in dynamically modelled studies have shown the efficacy of new, preventive strategies and debates about such approaches have improved the standard of care. In this review, we discuss what oncologists can learn from the HIV epidemic.
Adolescent↗
Insights into the molecular biology and sero-epidemiology of Kaposi's sarcoma.
PURPOSE OF REVIEW: Although the incidence of Kaposi's sarcoma in established market economies has fallen since the introduction of highly active antiretroviral therapy, it remains the most common tumour in individuals with HIV infection. Kaposi's sarcoma-associated herpesvirus is the aetiological agent of Kaposi's sarcoma and its role in the subversion of cellular machinery provides an understanding of the fundamental mechanisms involved in immunobiology and carcinogenesis. The focus of this review will be to discuss articles published from August 2001 to August 2002 that provide advances in our knowledge of this process, and also to review new data concerning the transmission and identification of Kaposi's sarcoma-associated herpesvirus infection in different populations. RECENT FINDINGS: We have an improved understanding of the epidemiologies of classic, endemic, post-transplant and AIDS-associated Kaposi's sarcoma. The role of specific genes in tumorigenesis has been further defined, with particular reference to the switch from latent to lytic infection and the involvement of cytokines and angiogenic factors. SUMMARY: Kaposi's sarcoma-associated herpesvirus is widespread in immunosuppressed individuals and is associated with significant morbidity and mortality. The study of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus represents an important model of the interplay between the immune system and cancer, and may lead to the development of clinically useful therapies including vaccines.
AIDS-Related Opportunistic Infections↗
Acquired immunodeficiency syndrome-related lymphoma in the era of highly active antiretroviral therapy.
The treatment and outcome of human immunodeficiency virus (HIV) infection altered dramatically in the mid-1990s with the introduction of highly active antiretroviral therapy (HAART). Highly active antiretroviral therapy, where available, has led to a dramatic decline in mortality from HIV and a decrease in the incidence of opportunistic infections and Kaposi sarcoma. This article addresses the effects that HAART has had on acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL). Metaanalysis of numerous cohort studies confirmed that the incidence of AIDS-related NHL has decreased since the advent of HAART. This decline is most marked for primary cerebral lymphomas and systemic immunoblastic lymphoma but has not been demonstrated for Burkitt lymphoma. In addition to genetic predisposing factors, age, nadir CD4 cell count, and lack of HAART therapy predict the development of NHL. The clinical presentation of AIDS-related NHL has not changed, but several institutions have reported an improvement in survival since the introduction of HAART. Moreover, HAART has been combined safely with systemic chemotherapy in the management of NHL, and this approach results in a more modest decrease in immune function than when chemotherapy is administered alone. This has led to a more aggressive approach to the management of AIDS-related NHL and response rates and overall survival durations that are approaching those seen in stage-matched high-grade lymphomas in the immunocompetent population.
Antiretroviral Therapy, Highly Active↗
The immunological effects of concomitant highly active antiretroviral therapy and liposomal anthracycline treatment of HIV-1-associated Kaposi's sarcoma.
A combination of highly active antiretroviral therapy (HAART) and liposomal anthracycline chemotherapy is the standard of care for advanced HIV-associated Kaposi's sarcoma, despite concerns that the chemotherapy may adversely affect lymphocyte subsets and HIV viraemia. We showed in 50 patients that liposomal anthracyclines used with HAART did not lead to a significant loss of CD4 or CD8 cells or an increase in HIV-1 viral load during or up to 12 months after chemotherapy.
Adult↗
Effects of combination chemotherapy and highly active antiretroviral therapy on immune parameters in HIV-1 associated lymphoma.
OBJECTIVE: To measure the effects of combined chemotherapy and highly active antiretroviral therapy (HAART) on immune cell counts and plasma HIV-1 RNA loads in patients with AIDS-related lymphoma (ARL) to determine the implications for opportunistic infection prophylaxis and medium-term immune function. DESIGN AND METHODS: Peripheral blood total lymphocyte count, CD4 T-cell count, CD8 T-cell count, CD19 B-cell count, CD16/CD56 natural killer cell count and plasma HIV-1 RNA load were prospectively measured at ARL diagnosis, at 1 and 3 months during and 1, 3 and 6 months after chemotherapy in twenty patients receiving HAART. RESULTS: Significant declines in T-helper cell (CD4) count, natural killer cell (CD16/CD56) and B lymphocyte count (CD19 cells) occurred during the first 3 months of chemotherapy. There was no significant alteration in the T-cytotoxic cell (CD8) count, CD4 percentage or HIV-1 RNA load during the study period. The T-helper cell and natural killer cell counts recovered to pre-treatment levels within 1 month of finishing chemotherapy. The recovery of B-cells was slower with pre-treatment levels only being achieved after 3 months. The recovery of CD4 T-cell count following completion of chemotherapy was more rapid than described for ARL patients who were not receiving concomitant HAART. CONCLUSIONS: By combining chemotherapy with HAART, immune function is better maintained in the medium term. The CD4 T-cell count falls by 50% during chemotherapy and this will help to identify patients who require opportunistic infection prophylaxis during chemotherapy.
Adult↗
Virological suppression at 6 months is related to choice of initial regimen in antiretroviral-naive patients: a cohort study.
BACKGROUND: Guidelines recommend both protease inhibitor (PI)- and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens for initial therapy in HIV-positive individuals whilst clinical trial data comparing treatment options remain limited. OBJECTIVE: To assess whether drug selection (PI versus NNRTI) in antiretroviral-naive patients is related to virological response at 6 months within a clinical cohort. DESIGN: Databases from two large clinics were used to identify all treatment-naive patients initiating highly active antiretroviral therapy (PI/ two PI or NNRTI). Statistical models determined the likelihood of suppressing HIV viral load < 500 copies/ml, the risk of treatment failure by 6 months, and factors associated with treatment success. RESULTS: Of 1109 potentially eligible patients 888 met study criteria and were included; 484 were prescribed a PI (40% indinavir, 41% nelfinavir) and 404 were prescribed NNRTI (40% efavirenz, 60% nevirapine). Three treatment arms were compared: efavirenz versus nevirapine versus PI. After stratification by year and centre and adjustment for baseline variables, only treatment group and baseline viral load remained significantly associated with virological suppression at 6 months. Patients on efavirenz were significantly more likely to achieve an undetectable viral load than those on PI or nevirapine. The relative hazard for nevirapine was 0.77 (95% confidence interval, 0.61-0.96, P = 0.02) and that for PI was 0.74 (95% confidence interval, 0.58-0.94, P = 0.01). Efavirenz also performed better in the analysis of treatment failure at 6 months. CONCLUSION: Although observational cohort data may be susceptible to significant bias, this study suggests a better initial virological response for efavirenz compared to either nevirapine or the PI. Clinical trial data is required to confirm these findings.
Adult↗
The management of lymphoma in the immunosuppressed patient.
Two forms of acquired immunodeficiency have dominated the last quarter of the twentieth century and are responsible for the majority of lymphomas in the immunosuppressed: post-transplantation lymphoproliferative disorders (PTLD) and AIDS-related lymphomas (ARL). The central role of Epstein-Barr virus in PTLD has led to novel treatment strategies designed to enhance immunity to this virus both as prevention and therapy. This is achieved by reducing iatrogenic immunosuppression and adoptive immunotherapy with allogeneic cytotoxic T-lymphocytes. Improved immune function in HIV seropositive patients treated with highly active antiretroviral therapy appears to be reducing the relative risk of AIDS-related lymphoma. However, ARL will remain a frequent diagnosis with the rapidly rising incidence of HIV throughout the world. The clinical management requires expertise in both the lymphoma chemotherapy and the treatment of HIV, including antiretroviral therapy and opportunistic infection management. Modest improvements in survival have been achieved recently for ARL.
Brain Neoplasms↗
Current Management of AIDS Related Non Hodgkin's Lymphoma.
Non Hodgkin's lymphoma is the AIDS defining illness in 3-3.5% of patients and is increasing in incidence as the survival of HIV infected people improves. The incidence of these intermediate/high grade B cell malignancies is sixty times higher than in the general population. The most important prognostic factors are a CD4 positive lymphocyte count of <100 cells/mm3, a prior AIDS defining diagnosis, an ECOG performance status >2 and primary cerebral origin. Patients with any of these factors are most likely to benefit from palliative rather than radical treatment. Good prognosis patients have a 30-40% chance of cure from their lymphoma with carefully administered intensive chemotherapy.
Journal Article↗