Divergent in vitro and in vivo correlates of HIV-specific T-cell responses during onset of HIV viraemia.
BACKGROUND
Cellular immune responses to HIV-1 have been examined mainly in peripheral blood mononuclear cells (PBMC). During onset of HIV replication and antigenaemia after discontinuation of highly active antiretroviral therapy (HAART), PBMC may theoretically contain HIV-specific T cells that are qualitatively and quantitatively different from specific T cells dominating in the tissues. PBMC responses throughout HIV immunotherapy trials may therefore be skewed during recurrent viraemia.


OBJECTIVE
To compare cellular HIV-specific in vitro responses in PBMC during onset of HIV viraemia with corresponding in vivo responses, represented by classical delayed-type hypersensitivity tests (DTH).


METHODS
HIV patients (n = 38), pre-immunized with four HIV-1 p24-like consensus peptides (Vacc-4x) during HAART, were subjected to a 14-week treatment interruption with recurrent HIV viraemia. Proliferative T-cell responses to Vacc-4x p24 peptides, HIV p24 protein, and cytomegalovirus (CMV) proteins were measured in PBMC. Corresponding Vacc-4x peptide DTH were expressed as skin infiltrate areas after 48 h.


RESULTS
After 14 weeks without HAART, HIV-1 RNA increased to 72,500 copies/ml (median). The Vacc-4x p24 peptide- and HIV-1 p24 protein-induced T-cell proliferation concurrently decreased by 81 and 93% in PBMC during viraemia (medians, P < or = 0.03), whereas proliferative responses to CMV antigens were stable. In contrast, the Vacc-4x DTH areas, rather tended to increase by 36% (P = 0.08) and contained infiltrates dominated by proliferating T cells and macrophages.


CONCLUSIONS
Divergent in vitro and in vivo HIV-specific cellular immune responses were found during recurrent HIV viraemia. The clinical relevance of both surrogate markers for HIV-related immune responses should be compared in future studies.
Kvale
Dag
D
Department of Infectious Diseases, Ullevål University Hospital, University of Oslo, Oslo, Norway. dag.kvale@medisin.uio.no
Kran
Anne-Marte Bakken
AM
Sommerfelt
Maja A
MA
Nyhus
Jørgen
J
Baksaas
Ingebjørg
I
Bruun
Johan N
JN
Sørensen
Birger
B
D016915:AIDS Vaccines; D023241:Antiretroviral Therapy, Highly Active; D049109:Cell Proliferation; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D014766:Viremia / Q000276:immunology*; D014779:Virus Replication
D016915:AIDS Vaccines; C494182:Vacc-4x