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Therapy Insight: AIDS-related malignancies—the influence of antiviral therapy on pathogenesis and management

Nature Clinical Practice Oncology volume 2, pages 406–415 (2005)Cite this article

Abstract

Patients with HIV infection are at an increased risk of a number of malignancies, including Kaposi's sarcoma (KS) and certain B-cell lymphomas. Most of these tumors are caused by oncogenic DNA viruses, including KS-associated herpesvirus and Epstein–Barr virus. HIV contributes to the development of these tumors through several mechanisms, including immunodeficiency, immunodysregulation, and the effects of HIV proteins such as Tat. The development of highly active antiretroviral therapy (HAART) has reduced the incidence of many HIV-associated tumors and has generally improved their responsiveness to therapy. However, the number of people living with AIDS is increasing, and it is possible that the number of AIDS-associated malignancies will rise and the pattern of tumors will change as more people live longer with HIV infection. The goal of KS therapy is long-term tumor control with minimal toxicity. HAART is an important component of this therapy, and some patients do not require other KS-specific therapies. By contrast, the goal of AIDS-related lymphoma therapy in most cases is the attainment of a complete response with curative intent, and the benefits of administering HAART during therapy must be weighed against possible disadvantages. The past decade has seen substantial improvements in the treatment of AIDS-related lymphoma, which is attributed partially to a shift in tumor type and more effective regimens. There is currently an interest in developing new therapies for HIV-associated malignancies, based on viral, vascular or other pathogenesis-based targets.

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Figure 1: Trends in the incidence of AIDS, the number of AIDS-related deaths, and the prevalence of AIDS in the US from 1985 to 2003.

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Author information

Authors and Affiliations

  1. HIV and AIDS Malignancy Branch,

    Robert Yarchoan, Giovanna Tosato & Richard F Little

  2. HIV and AIDS Malignancies Branch,

    Robert Yarchoan, Giovanna Tosato & Richard F Little

  3. Molecular and Cell Biology Section of the Experimental Transplantation and Immunology Branch, at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Robert Yarchoan, Giovanna Tosato & Richard F Little

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  1. Robert Yarchoan
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  2. Giovanna Tosato
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  3. Richard F Little
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Correspondence to Robert Yarchoan.

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Competing interests

Co-authors of this article are co-inventors on one or more patents involving the use of certain antiviral drugs including didanosine and zalcitabine; on the use of IL-12 to treat KS; on an assay for KSHV viral IL-6; and on certain antiangiogenic and pro-hematopoeitic therapies not yet in clinical trial. These inventions were made when they were full-time employees of the US government under 45 Code of Federal Regulations Part 7. All rights, title, and interest to these patents have been assigned to the US government. The government conveys a portion of the royalties it receives to its employee inventors under the Federal Technology Transfer Act of 1986 (P.L. 99-502). Moreover, some of the authors' research has been supported by Clinical Trial Agreements or Cooperative Research and Development Agreements with companies that include Genetics Institute, Bristol-Myers Squibb Co., Celgene Corporation, Japan Energy Corporation, and US Bioscience Corp.

Glossary

TAT PROTEIN

A trans-activating factor of HIV that is also an extracellular molecule, which can modulate gene expression, cell survival, growth, transformation, and angiogenesis

SPINDLE CELLS

Elongated cells characteristic of certain tumors

OPEN READING FRAME

A long DNA sequence that is uninterrupted by a stop codon, and has the potential to encode a protein or polypeptide

G-PROTEIN-COUPLED RECEPTOR

Cell-surface receptors that are coupled to G proteins and have seven membrane-spanning domains, often stimulating or inhibiting the activity of downstream enzymes; G proteins consist of three subunits: the α-subunit, which contains the GTP-binding site; the β-subunit, and the γ-subunit

VIRAL LATENT GENES

Viral genes that are expressed during a state of infection (called the latent state), during which the virus persists in a cell but does not replicate

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI)

Antiretroviral drugs that are nucleoside analogs and act by inhibiting the essential and unique viral protein reverse transcriptase, which makes a DNA copy of RNA

ZIDOVUDINE

A nucleoside reverse transcriptase inhibitor, also called azidothymidine, which is used to treat HIV infection; the first effective AIDS drug to be developed

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME

Transient worsening of an AIDS-related complication caused by an immune response associated with the HAART-associated immune reconstitution

CRYOTHERAPY

A surgical technique that uses freezing with argon gas or liquid nitrogen to destroy or excise tissue

PHOTODYNAMIC THERAPY

Use of light and a photosensitizing drug, such as porfirmer sodium, to ablate abnormal tissue

CIDOFOVIR

An antiviral medication used for the treatment of cytomegalovirus infection

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Yarchoan, R., Tosato, G. & Little, R. Therapy Insight: AIDS-related malignancies—the influence of antiviral therapy on pathogenesis and management. Nat Rev Clin Oncol 2, 406–415 (2005). https://doi.org/10.1038/ncponc0253

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