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.
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.


METHODS
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-gamma 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.


CONCLUSIONS
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.
Bihl
Florian
F
Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.
Mosam
Anisa
A
Henry
Leah N
LN
Chisholm
John V
JV
Dollard
Sheila
S
Gumbi
Pamela
P
Cassol
Edana
E
Page
Taryn
T
Mueller
Nicolas
N
Kiepiela
Photini
P
Martin
Jeff N
JN
Coovadia
Hoosen M
HM
Scadden
David T
DT
Brander
Christian
C
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology