Session 29Oral Abstract Presentations Topics in Primary HIV Infection Session Day and Time: Thursday 10 - 11 am Presentation Time: 10:00 Room: Ballroom B
151 Kinetics of HIV-Specific CD4+ T-cell Responses in Subjects Treated with HAART during Primary HIV Infection D. Kaufmann*, P. Bailey, C. Brander, H. Truong, D. Strick, M.Johnston, M.Altfeld, B. Walker, E. Rosenberg Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA
Background: Increasing evidence suggests that HIV-specific CD4+ T-cell responses in addition to CD8 CTL are critical for effective immune control of HIV infection. However, comprehensive analyses of CD4 responses during primary HIV infection (PHI) are lacking. A better understanding of these responses and of the impact of early initiation of HAART may provide important insight into the immunopathogenesis of HIV infection.
Methods: Fresh CD8-depleted PBMCs from 9 patients (pts) with documented PHI were screened for HIV-specific CD4 responses by IFN-gamma ELISpot using pools of overlapping peptides spanning all expressed HIV proteins (HIV-1 clade B consensus sequence).
Results: Nine (9) subjects diagnosed during acute HIV infection were studied; 8 of 9 study subjects were treated with HAART at the time of diagnosis. All subjects presented with acute retroviral syndrome. The first available time point for immunological studies before HAART (baseline, BL) was at a median of 12 (range 5-24) days following onset of clinical symptoms (DFOS). Six (6) of 9 individuals had a viremia > 750,000 copies/mL, and all subjects had a negative or incomplete Western blot. At BL before initiation of HAART, the total magnitude of HIV-specific CD4 responses assessed in IFN-gamma ELISpot assays ranged from 315-8,650 (median 2,730) SFC/106 CD8- depleted PBMCs, and there was no significant correlation with DFOS. Responses were dominated by gag and nef with a wide spectrum of specificities. At 1 mo after BL, evaluable subjects (n = 6) showed a loss of responses in magnitude (range -15% to -81%; median -64%), whereas breadth of responses was less affected (range -53% to +30%; median -30%). At 3 mos after BL, the total magnitude of responses stabilized in 3/5 pts studied longitudinally, whereas in 2 others it continued to decline. While the magnitude stabilized, a further decline in breadth of responses was observed in 4/5 pts with only a few new responses generated compared to BL.
Conclusions: Our findings demonstrate that most of the pts studied have broad and robust HIV-specific T-helper cell responses at the time of diagnosis of PHI. However, while on therapy, in some individuals these responses wane in magnitude and breadth, suggesting that additional manipulation of the immune system may be necessary to preserve and augment HIV-specific CD4 responses.
