Short- and long-term effects of highly active antiretroviral therapy on Kaposi sarcoma-associated herpesvirus immune responses and viraemia.
OBJECTIVE
To investigate the effect of highly active antiretroviral therapy (HAART) on Kaposi sarcoma-associated herpesvirus (KSHV) DNA load, anti-KSHV antibody responses and KSHV-specific CD8 T cell responses in HIV-infected individuals over a 2 year period.


METHODS
Prospective study of 27 HIV-infected antiretroviral therapy-naive individuals, with (n = 4) and without KS (n = 23), before HAART and at 3-month intervals, during treatment with HAART.


METHODS
Sequential blood samples were collected for anti-KSHV antibody detection, KSHV DNA load in peripheral blood mononuclear cells (PBMC) and plasma, HIV Gag-specific and KSHV-specific CD8 T cell responses, HIV-1 plasma RNA load and CD4 and CD8 T cell counts.


RESULTS
KSHV DNA in PBMC and plasma became less detectable over time during HAART, in particular after 12 months. KSHV DNA was undetectable in plasma after 24 months on HAART. Anti-KSHV lytic, but not latent, antibody levels increased within 12 months of treatment. KSHV-specific CD8 T cell responses were absent prior to HAART but became detectable in some patients within 6 months of starting treatment, and continued to increase thereafter.


CONCLUSIONS
HAART (both protease inhibitor-based and non-nucleoside reverse transcriptase inhibitor-based antiretroviral combinations) is associated with immune reconstitution to KSHV and with undetectable KSHV viraemia. However, this restoration is apparent (in particular) only after a relatively long (> 24 months) period of treatment. These immune responses could contribute to the decreased incidence of KS during HAART, but it is unlikely to be a complete explanation for the often rapid resolution of KS when HAART is started.
Bourboulia
Dimitra
D
Wolfson Institute for Biomedical Research and the Department of Sexually Transmitted Diseases, University College London, London, UK.
Aldam
Diana
D
Lagos
Dimitrios
D
Allen
Elizabeth
E
Williams
Ian
I
Cornforth
David
D
Copas
Andrew
A
Boshoff
Chris
C
D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012514:Sarcoma, Kaposi / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000276:immunology* / Q000821:virology
D000914:Antibodies, Viral; D004279:DNA, Viral