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

Brandt, Lea PhD*; Benfield, Thomas MD, DMSc†,‡; Kronborg, Gitte MD; Gerstoft, Jan MD§; Fomsgaard, Anders MD, DMSc*,‖; Karlsson, Ingrid PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2013 - Volume 63 - Issue 4 - p 418–427
doi: 10.1097/QAI.0b013e31828fa22b
Basic and Translational Science

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.

*Department of Virology, Statens Serum Institut, Copenhagen, Denmark;

Department of Infectious Diseases and Clinical Research Center, Hvidovre University Hospital, Hvidovre, Denmark;

Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;

§Department of Infectious Diseases, University Hospital Copenhagen, Copenhagen, Denmark; and

Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.

Correspondence to: Ingrid Karlsson, PhD, Department of Virology, Building 351/209, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark (e-mail: iks@ssi.dk).

Presented in part at the Keystone Symposia on Molecular and Cellular Biology—HIV Vaccine, March 21–26, 2012, Keystone, CO.

The authors have no conflicts of interest to dislcose.

Supported by grants from the Danish International Development Agency, the European and Developing Countries Clinical Trials Partnership, and the Danish AIDS Foundation.

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Received October 12, 2012

Accepted February 27, 2013

© 2013 by Lippincott Williams & Wilkins