HIV-1–Infected Individuals in Antiretroviral Therapy React Specifically With Polyfunctional T-Cell Responses to Gag p24

TY - JOUR

T1 - HIV-1–Infected Individuals in Antiretroviral Therapy React Specifically With Polyfunctional T-Cell Responses to Gag p24

AU - Brandt, Lea

AU - Benfield, Thomas

AU - Kronborg, Gitte

AU - Gerstoft, Jan

AU - Fomsgaard, Anders

AU - Karlsson, Ingrid

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Background:: Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine. METHODS:: In this study, the magnitude, breadth, and quality of the HIV-1-specific T-cell response in HIV-1-infected viremic individuals (n = 19) and individuals on highly active antiretroviral treatment (HAART) (n = 14) using multicolor flow cytometry were determined. RESULTS:: We found that magnitude and breadth of the CD8 T-cell response were significantly higher in viremic individuals than individuals on HAART (P < 0.0001 and P < 0.0001, respectively) and that the functionality of the overall HIV-1-specific response was significantly different in individuals on HAART and viremic individuals (P = 0.0020). In individuals on HAART, the remaining responses were primarily detected upon stimulation with overlapping peptides from Gag p24, integrase, and Nef. The Gag p24 response was more polyfunctional than corresponding responses observed in viremic individuals. CONCLUSIONS:: Identification of highly immunogenic regions also recognized by individuals on HAART may be important for HIV-1 vaccine development. Irrespective of HLA haplotype, specific regions within the HIV-1 genome that is targeted more frequently in individuals on HAART have been identified. However, further studies are required to establish if these particular regions could be interesting for a future vaccine that might limit the time and opportunity for escape mutations.

AB - Background:: Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine. METHODS:: In this study, the magnitude, breadth, and quality of the HIV-1-specific T-cell response in HIV-1-infected viremic individuals (n = 19) and individuals on highly active antiretroviral treatment (HAART) (n = 14) using multicolor flow cytometry were determined. RESULTS:: We found that magnitude and breadth of the CD8 T-cell response were significantly higher in viremic individuals than individuals on HAART (P < 0.0001 and P < 0.0001, respectively) and that the functionality of the overall HIV-1-specific response was significantly different in individuals on HAART and viremic individuals (P = 0.0020). In individuals on HAART, the remaining responses were primarily detected upon stimulation with overlapping peptides from Gag p24, integrase, and Nef. The Gag p24 response was more polyfunctional than corresponding responses observed in viremic individuals. CONCLUSIONS:: Identification of highly immunogenic regions also recognized by individuals on HAART may be important for HIV-1 vaccine development. Irrespective of HLA haplotype, specific regions within the HIV-1 genome that is targeted more frequently in individuals on HAART have been identified. However, further studies are required to establish if these particular regions could be interesting for a future vaccine that might limit the time and opportunity for escape mutations.

U2 - 10.1097/qai.0b013e31828fa22b

DO - 10.1097/qai.0b013e31828fa22b

M3 - Journal article

C2 - 23507659

SN - 1525-4135

VL - 63

SP - 418

EP - 427

JO - Journal of acquired immune deficiency syndromes (1999)

JF - Journal of acquired immune deficiency syndromes (1999)

IS - 4

ER -