Skip Navigation LinksHome > June 2007 - Volume 21 - Issue 10 > Kaposi's sarcoma-associated herpesvirus-specific immune reco...
doi: 10.1097/QAD.0b013e328182df03
Basic Science

Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma

Bihl, Floriana; Mosam, Anisac; Henry, Leah Na; Chisholm, John V IIIa; Dollard, Sheilae; Gumbi, Pamelag; Cassol, Edanai,k; Page, Tarynd; Mueller, Nicolasj; Kiepiela, Photinig; Martin, Jeff Nf; Coovadia, Hoosen Mh; Scadden, David Tb,l; Brander, Christiana

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Background: Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic in South Africa and the clinical manifestation of AIDS-associated Kaposi's sarcoma (KS) represents a significant clinical problem. Whereas the positive effects of HAART on the regression of KS have been well established, less is known about the role of herpesvirus-specific cellular immunity in disease improvement.

Design: Thirty-three treatment-naive HIV clade C-infected individuals with KS were randomly assigned into two treatment arms (HAART plus systemic chemotherapy versus HAART alone). KSHV-specific cellular immune responses, viral loads and clinical outcome were evaluated.

Methods: KSHV, Epstein–Barr virus and HIV-specific cellular immunity was measured using an IFN-γ enzyme-linked immunospot assay in samples obtained at baseline and up to 11 months after treatment initiation. Cell-associated KSHV viremia was determined by real-time polymerase chain reaction.

Results: Robust increases in CD4 cell counts and suppressed HIV viral loads were seen in parallel with significant increases in the KSHV-specific cellular immune responses over time. Although slowly increasing after 5 months, KSHV-specific T-cell responses were significantly elevated only after 11 months, with both lytic and latent antigens being more frequently targeted. A trend towards better clinical outcome with HAART plus chemotherapy treatment was observed compared with HAART alone, and was accompanied by a significant reduction in cellular KSHV viral load in the HAART plus chemotherapy-treated subjects but not those treated with HAART alone after 11 months of treatment.

Conclusion: The data show a temporal association between the clinical improvement of KS and the re-appearance of KSHV-specific cellular immunity, and demonstrate an effective suppression of KSHV viral replication using combination therapy.

© 2007 Lippincott Williams & Wilkins, Inc.


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