The New York case: lessons being learned.
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Disease Notification↗
Biomedical subjects
Paul A Volberding
Publications and source records attributed to Paul A Volberding.
Baboon bone-marrow xenotransplant in a patient with advanced HIV disease: case report and 8-year follow-up.
BACKGROUND: Xenotransplantation offers a solution to the shortage of organ donors and may offer resistance to human-specific pathogens. Baboons are resistant to productive infection with HIV-1. A baboon bone-marrow transplant (BMT) was performed in an attempt to reconstitute the immune system of a patient with advanced AIDS. The aims of this pilot study were to evaluate the safety of the procedure and develop an approach to prevent and monitor for xenozoonoses. METHODS: A source animal was selected on the basis of infectious disease surveillance protocols. Baboon bone marrow, engineered to remove graft-versus-host-disease-producing mature lineages, but to retain hematopoietic stem cells and facilitating cells, was infused into the patient after nonmyeloablative conditioning. Serial clinical, virologic, immunologic, and hematologic evaluations were performed. RESULTS: A 38-year-old male with advanced AIDS, who had failed to respond to triple-drug antiretroviral therapy, underwent baboon BMT in 1995. The patient tolerated the procedure without complication. Baboon cells were detected in the peripheral blood on days 5 and 13 after transplantation. Baboon endogenous virus (BaEV) was detected on day 5 but not subsequently. Antibody to BaEV was not detected. HIV-1 viral load declined 1.5 log and remained low until 11 months. The patient improved clinically, and no adverse events occurred. The patient is alive 8 years after the procedure. CONCLUSIONS: Baboon BMT to treat AIDS was attempted using nonmyeloablative conditioning and resulted in transient microchimerism and clinical and virologic improvements. Long-term improvement was not achieved; however, no adverse events occurred, and no evidence of transmission of xenogeneic infections was found.
Acquired Immunodeficiency Syndrome↗
Epoetin alfa for treatment of anemia in HIV-infected patients: past, present, and future.
Despite the availability of highly active antiretroviral therapy and the resulting reduction in severe anemia associated with HIV infection, epoetin alfa has continued to play an important role in the management of HIV-infected patients. Mild-to-moderate anemia remains common, and its correction with epoetin alfa has resulted in significant improvements in quality of life, physical functioning, and possibly prolongation of survival. New research has demonstrated that epoetin alfa may have therapeutic potential beyond its ability to stimulate erythropoiesis due to its neuroprotective and antiapoptotic properties. Current and future research will further clarify the role of epoetin alfa in the clinical management of the HIV-infected population.
Anemia↗
Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel.
CONTEXT: Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection. OBJECTIVE: To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails. DATA SOURCES: Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management. STUDY SELECTION: Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004. DATA EXTRACTION: Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached. DATA SYNTHESIS: Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel). CONCLUSION: Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.
Adult↗
Anemia in HIV infection: clinical impact and evidence-based management strategies.
Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.
Anemia↗
Initiating HIV therapy. Timing is critical, controversial.
Currently available antiretroviral drug regimens are able to suppress HIV replication and allow CD4 recovery in the vast majority of patients with HIV infection. The challenge is to match each patient to the regimen that is most likely to durably suppress HIV replication enough to prevent resistance selection without causing treatment-limiting toxicities. It is also critical, but difficult, to know when to begin treatment relative to CD4 cell count and plasma viral load. In this article, Dr Volberding addresses the central questions surrounding antiretroviral treatment initiation and reviews some available treatment options.
Anti-Retroviral Agents↗
Opportunities and options for treatment research in resource-constrained settings.
HIV clinical research faces limitations even in research-rich settings. Even though important questions remain unanswered, clinical trials will probably never be conducted that address, prospectively, when treatment is optimally indicated, for example. In resource-constrained settings, large, prospective clinical trials are also unlikely. On the other hand, ones with a more observational design or that compare cohort experiences may well be feasible and able to provide information important in those settings, as well as in regions with abundant financial resources.
Anti-HIV Agents↗
HIV therapy in 2003: consensus and controversy.
HIV therapy has well-established and substantial clinical benefits. Awareness of these benefits has brought many infected persons into care. Many more infected persons would be treated were it not for the frequent side effects associated with antiretroviral drugs. All antiretroviral agents can cause both short-term and long-term toxicities. This is a particularly vexing problem as current data does not allow accurate predictions of treatment toxicities and, in many cases, side effects are only partially reversible. Moreover, therapy is frequently associated with the selection of drug-resistant viral isolates and incomplete viral suppression. This is commonly caused by inadequate medication adherence and leads to increasingly severe virologic failure. The present review will address both the striking advantages of HIV therapy as well as the ongoing challenges in its application.
Antiretroviral Therapy, Highly Active↗
The pavia consensus statement.
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Antiretroviral Therapy, Highly Active↗
Human immunodeficiency virus hematology.
The advent of potent antiretroviral therapy has altered the expected natural history of human immunodeficiency virus (HIV) infection and of many previously associated opportunistic complications, including malignancies. At the same time, HIV suppression has not affected all of these complications equally and the longer expected survival of infected patients may allow the development of newer complications. Additionally, the use of potent antiretroviral combination therapy may itself lead to hematological toxicities. Together these changes affect the consultation role of the hematology-oncology specialist in comprehensive HIV care and demand ongoing education. In Section I, Dr. Paul Volberding reviews the biology of antiretroviral drug development and the progression in discovering new agents as the viral life cycle is further elucidated. He briefly summarizes the process of combining agents to achieve the degree of viral suppression required for long-term clinical benefit. In Section II, Dr. Kelty Baker reviews the effects of HIV and its therapy on hematologic dyscrasia and clotting disorders. She summarizes how therapy may decrease certain previously common manifestations of HIV disease while adding new problems likely to result in referral to the hematologist. In addition, she addresses the role of secondary infections, such as parvovirus, in this spectrum of disorders. In Section III, Dr. Alexandra Levine discusses the still challenging aspects of HIV associated non-Hodgkin's lymphoma and the association between HIV infection and Hodgkin's disease. She addresses current controversies in the pathogenesis of HIV related lymphomas and summarizes a number of recent trials of combination chemotherapy, with or without monoclonal antibodies, in their management. Additionally, she reviews the complex relationship of HIV disease with multicentric Castleman's disease and recent attempts to manage this disorder.
Anti-Retroviral Agents↗
Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel.
OBJECTIVE: New information warrants updated recommendations for the 4 central issues in antiretroviral therapy: when to start, what drugs to start with, when to change, and what to change to. These updated recommendations are intended to guide practicing physicians actively involved in human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related care. PARTICIPANTS: In 1995, physicians with specific expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care were invited by the International AIDS Society-USA to serve on a volunteer panel. In 1999, others were invited to broaden international representation. The 17-member panel met regularly in closed meetings between its last report in 2000 and April 2002 to review current data. The effort was sponsored and funded by the International AIDS Society-USA, a not-for-profit physician education organization. EVIDENCE AND CONSENSUS PROCESS: The full panel was convened in late 2000 and assigned 7 section committees. A section writer and 3 to 5 section committee members (each panel member served on numerous sections) identified relevant evidence and prepared draft recommendations. Basic science, clinical research, and epidemiologic data from the published literature and abstracts from recent (within 2 years) scientific conferences were considered by strength of evidence. Extrapolations from basic science data and expert opinion of the panel members were included as evidence. Draft sections were combined and circulated to the entire panel and discussed in a series of full-panel conference calls until consensus was reached. Final recommendations represent full consensus agreement of the panel. CONCLUSIONS: Because of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease. However, the optimal time to initiate therapy remains imprecisely defined. Availability of new drugs has broadened options for therapy initiation and management of treatment failure, which remains a difficult challenge.
Adjuvants, Immunologic↗
Does hepatitis C virus infection increase the risk of HIV disease progression?
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Antiretroviral Therapy, Highly Active↗
Who cares for AIDS?
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Clinical Competence↗