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Longitudinal Assessment of Changes in HIV-Specific Effector Activity in HIV-Infected Patients Starting Highly Active Antiretroviral Therapy in Primary Infection ¹

Galit Alter^*, George Hatzakis^*, Christos Micheal Tsoukas^*, Karen Pelley^*, Danielle Rouleau, Roger LeBlanc^*, Jean-Guy Baril, Harold Dion, Eric Lefebvre, Réjean Thomas, Pierre Côté, Normand Lapointe^¶, Jean-Pierre Routy^*, Rafik-Pierre Sékaly^||, Brian Conway^# and Nicole Flore Bernard^2,*

^* McGill University Health Center, Montreal, Quebec, Canada; Center Hospitalier de l’Université de Montreal, Montreal, Quebec, Canada; Clinique Médical du Quartier Latin, Montreal, Quebec, Canada; Clinique l’Actuel, Montreal, Quebec, Canada; ^¶ Hôpital Ste. Justine, Montreal, Quebec, Canada; ^|| University of Montreal, Montreal, Quebec, Canada; and ^# University of British Columbia, Vancouver, British Columbia, Canada

Both the magnitude and breadth of HIV-specific immunity were evaluated longitudinally on samples collected from six subjects starting highly active antiretroviral therapy (HAART) preseroconversion (group 1), 11 recently infected subjects starting HAART postseroconversion (group 2), five subjects starting HAART in the second half of the first year of infection (group 3), and six persons starting treatment in the chronic phase of infection (group 4). HIV-specific immunity was measured by IFN- ELISPOT, detecting the frequency of cells responding to a panel of HLA-restricted HIV-1 peptides. Intracellular cytokine staining was used to detect the frequency of HIV-1 Gag p55-specific CD4⁺ and CD8⁺ T cells in a subset of participants. The magnitude and breadth of HIV-specific responses persisted in all group 1 subjects and in 5 of 11 (45%) group 2 subjects. Both of these parameters declined in 6 of 11 (55%) group 2 and in all group 3 and 4 individuals. All persons who maintained detectable numbers of HIV-1 Gag p55-specific CD4⁺ and CD8⁺ T cells after starting HAART preserved the intensity and breadth of their HIV-specific effector response. Our results show that HIV-specific immunity can be preserved even if HAART is initiated beyond the acute phase of infection.

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