Background:
Starting antiretroviral therapy (ART) during acute HIV infection (AHI) is known to limit damage to the immune system and lower the size of the viral reservoir. In light of HIV cure interventions, it is important to understand the longitudinal dynamics of the early host immune responses in relation to the viral reservoir size. Therefore, we investigated the viral reservoir size and HIV specific immune responses in participants of the Netherlands Cohort Study on Acute HIV Infection (NOVA study), who initiated ART immediately after diagnosis of AHI.
Methods:
Participants in the NOVA study diagnosed during Fiebig II-VI were included in the analysis (n=22). PBMC from leukapheresis at 24 and 156 weeks after initiation of ART were analyzed. Viral reservoir size was assessed by Intact Proviral DNA Assay and qPCR. HIV specific precursor T-cell responses after HIV peptide pool stimulation (Env, Gag, Nef, Pol) were determined by flowcytometry. Correlations were determined using Pearson’s correlations (p<0.05).
Results:
A mean decline in intact proviral DNA (Fig.1A) and total HIV-DNA load, but not defective proviral DNA and cell-associated US-RNA between 24 and 156 weeks after ART initiation was observed. We measured a positive HIV specific CD4+ and CD8+ T-cell response to at least 3 different viral proteins in the majority of individuals at both time points (Fig.1 B+C). At 24 weeks, intact proviral DNA load was associated with CD4+ T-cell responses to Env (p<0.001, R2=0.96), Gag (p=0.005, R2=0.6), Nef (p<0.001, R2=0.9) and Pol (p=0.002, R2=0.6). At 156 weeks, intact proviral DNA load was correlated with CD8+ T-cell response to Gag (p=0.034, R2=0.59) and Pol (p<0.001, R2=0.77). Moreover, we observed a positive association between the decay of intact proviruses between 24 and 156 weeks with CD4+ T-cell responses to Env (p=0.034, R2=0.64) and Nef (p=0.007, R2=0.76). No associations between T-cell responses and other viral reservoir measurements (defective proviral DNA load, total HIV-DNA and US-RNA) were observed.
Conclusions:
We detected a positive association between HIV specific T-cell responses and the decay of intact proviral DNA load in individuals treated during AHI. This implies that a potent HIV specific T-cell response, in addition to early ART, leads to a reduction of intact proviral DNA load. This finding potentially provides a promising avenue for cure interventions aimed at reservoir induction in combination with T-cell activating strategies.
