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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

doi: 10.1097/QAD.0b013e328182df03
Basic Science

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.

From the aPartners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, USA

bCenter for Regenerative Medicine and Technology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA

cDepartment of Dermatology, South Africa

dHIV Pathogenesis Program, Doris Duke Medical Research Institute, South Africa

eDepartment of Virology, South Africa

fCentre for HIV/AIDS Research, Faculty of Health Science, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

gCenters for Disease Control and Prevention, Atlanta, Georgia, USA

hAIDS Immunopathogenesis Unit DIBIT, San Raffaele Scientific Institute, Milan, Italy

iDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland

jHIV-1 Immune Pathogenesis and Therapeutics Research Program, University of Pretoria, Pretoria, South Africa

kDepartments of Epidemiology and Biostatistics, University of California, San Francisco, California, USA

lHarvard Stem Cell Institute, Boston, Massachusetts, USA.

Received 10 October, 2006

Revised 7 March, 2007

Accepted 16 March, 2007

Correspondence to Christian Brander, PhD, Partners AIDS Research Center, Building149, 13th Street, Charlestown, MA 02129-2000, USA. Tel: +1 617 724 5789; fax: +1 617 726 5411; e-mail: cbrander@partners.org

The first two authors contributed equally to this work.

© 2007 Lippincott Williams & Wilkins, Inc.