OA05.04
Background: High viral load (VL) and rapid loss of CD4+ T cells are a hallmark of acute HIV infection. The association between the subsequent emergence of HIV-specific CD8+ T cells and the decrease in VL support that CD8+ T cells are crucial in the initial control of viral replication. However, little is known about the kinetics of emerging T cell responses during early acute infection (Fiebig [F] I to III) and the effect of early initiation of antiretroviral treatment (ART) on the development of HIV-specific T cells.
Methods: 28 patients with acute HIV infection (11 FI/II, 17 FIII) were enrolled in the RV254/Search 010 study and immediately received ART. HIV-specific immune responses against Gag and Env peptide pools were determined in PBMC using IFN-γ intracellular cytokine staining prior to ART initiation and 6 and 24 months post-ART.
Results: At time of diagnosis, no HIV-specific T cell responses were detected in FI/II, while in FIII predominantly Gag-specific CD4+ responses were observed in 2/17 (12%) and CD8+ responses in 4/17 (24%) patients. Median plasma VL in FI/II was 5.5 log10 copies/ml vs. 6.7 log10 copies/ml in FIII (p=0.001). At 6 and 24 months post-ART all patients had undetectable VL. However, 6 months post-ART there was no significant difference observed in the frequency of Gag-specific CD4+ and CD8+ responses between patients treated in FI/II (2/11 [18%] and 6/11 [55%], respectively), and FIII (4/17 [23%], and 8/17 [47%], respectively). The frequency of Gag-specific CD8+ T cell responses was maintained 24 months post-ART, primarily in patients that initiated ART in FIII (FI/II CD4+: 0/11, CD8+: 4/11 [36%]; FIII CD4+: 5/17 (29%), CD8+: 9/17 [53%] p>0.05).
Conclusions: HIV-specific T cell responses, primarily CD8+ mediated against Gag, were detected at FIII but not FI/II. However, after 6 months of ART, both groups had similar numbers of responders maybe due to viremia during the initial post-ART period or ongoing viral replication in privileged sites.
