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Justin Stebbing

Publications and source records attributed to Justin Stebbing.

90 records · Page 5Linked to original sources
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

New insights into the immunology and evolution of HIV.

Fewer than one million HIV infected individuals are currently receiving anti-retroviral therapy. The limitations of such treatment have underscored the need to develop more effective strategies to control the spread and pathogenesis of HIV. Typically, naturally occurring protective immune responses provide the for such development. It is now clear however that HIV can utilise the milieu of an activated immune system to its own replicative advantage. Mobilisation of the immune response, intended to thwart the virus, may instead fuel its dissemination, 'immune escape' and spread. The immense genetic variation of HIV contributes to lack of immune control and the development of progressive disease in the majority of infected, untreated individuals. Further delineation of the intimate interactions between the HIV and the immune system will be critical and recent advances in this direction are discussed.

Evolution, Molecular↗
PubMed2003

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↗
PubMed2003

Kaposi's sarcoma-associated herpesvirus cytotoxic T lymphocytes recognize and target Darwinian positively selected autologous K1 epitopes.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of Kaposi's sarcoma (KS) and certain lymphoproliferations particularly in the context of human immunodeficiency virus (HIV) type 1-induced immunosuppression. The introduction of effective therapies to treat HIV has led to a decline in the incidence of KS, suggesting that immune responses may play a role in controlling KSHV infection and pathogenesis. Cytotoxic-T-lymphocyte (CTL) activity against KSHV proteins has been demonstrated; however, the identification of KSHV CTL epitopes remains elusive and problematic. Although the herpesvirus genomic layout is generally conserved, KSHV encodes a unique hypervariable protein, K1, with intense biological selection pressure at specific amino acid sites. To investigate whether this variability is partly driven by cellular immunity, we designed K1 peptides that match only the unique viral sequence for every individual studied here (autologous peptides). We identified functional CTL epitopes within K1's most variable areas, and we show that a given individual responds only to autologous peptides and not to peptides from other individuals. Furthermore, these epitopes are highly conserved sequences within KSHV isolates from a specific strain but are not conserved between different strains. We conclude that CTL recognition contributes to K1, and therefore to KSHV, evolution.

Amino Acid Sequence↗
PubMed2003

Innate and adaptive immunological insights into HIV pathogenesis.

The human immunodeficiency virus is notorious for its ability to evade the immune system. As well as its ability to escape from cell-mediated and humoral immune responses, new insights are detailing its subversive, pernicious interactions with the innate immune system. The molecular mechanisms underlying these processes highlight potential therapeutic and vaccination strategies.

Antibody Formation↗
PubMed2003

HIV and AIDS in the People's Republic of China: a collaborative review.

The number of individuals diagnosed with HIV in China has risen dramatically in the last two years coincident with increased awareness and an attitude change within government. UNAIDS has suggested that China could have 10 million HIV infected people by 2010. However, antiretroviral treatments and HIV testing are not yet widely available and infected individuals often live in remote areas. It is unlikely that cheaper, locally produced, generic antiretroviral formulations will be available in China in the near future. Consequently, alternative strategies to manage HIV infection are being considered including the use of hydroxyurea, chloroquine and traditional Chinese herbal medicines. It is recognized in China that prevention and educational strategies will need to be at the forefront of approaches to control this epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Current treatment of HIV infection.

The field of antiretroviral therapy has witnessed remarkable progress during the past 15 years. There are now over a dozen approved therapeutic agents for infection with the human immunodeficiency virus (HIV), a pathogen that once caused nearly uniformly fatal illness. These agents usually target two essential enzymes of the virus, the reverse transcriptase and the protease. The era of potent antiretroviral therapy, also termed highly active antiretroviral therapy, began in 1996 and has been marked by dramatic declines in morbidity and mortality due to HIV disease in the developed world. These advances have not been without their cost in terms of drug resistance and toxicity and unwanted effects. Concern about these negative effects has led to a more conservative approach to the timing of the initiation of therapy and to clinical trials of intermittent therapy in an attempt to decrease the total exposure to drugs over time. Immune-based approaches such as therapeutic vaccination may someday permit viremia to be controlled in the absence of drugs. Antiviral potency has been the key to the initial success of drug regimens, as well as to the durability of their success, the restoration of immune function, the prevention of the emergence of resistance, and ultimately the prevention of disease progression. Future progress in antiretroviral therapy will bring more choices for physicians and patients and will make an already complex field both more challenging and more rewarding.

Anti-HIV Agents↗
PubMed2003

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↗
PubMedDate not supplied

The clades of HIV: their origins and clinical significance.

It is over 20 years since the identification of HIV as the causative agent of AIDS. Despite the innovation and perseverance of biomedical researchers, HIV has cumulatively infected over 60 million individuals and caused the deaths of over 28 million, the majority in the developing world. There is perhaps no greater need in medical science than the development of more effective treatments for HIV and, ultimately, a protective vaccine. The spread of an extraordinary range of variants of HIV has implications for diagnosis and therapy. As the availability of antiretrovirals increases, data on the clinical response to treatment for non-B subtype infections has increasing relevance. Efficient targeting of the extreme genetic diversity of HIV-1, and an understanding of the processes underlying this, represents one of the major challenges in the control of this ongoing pandemic.

AIDS Vaccines↗