Cytokine and Chemokine Signature in Elite versus Viremic Controllers infected with HIV

BACKGROUND: HIV long-term non-progressors (LTNP) maintaining high CD4+ T-cell counts without antiretroviral therapy (ART)) are divided into elite controllers (EC) with undetectable and viremic controllers (VC) with low viral loads. Little is known about the long-term changes of T-cell subsets and inflammation patterns in EC versus VC. Objective To explore the long-term evolution of CD4+ T-cell levels in LTNP and to analyze cytokine profiles in EC versus VC.

SUBJECTS AND METHODS: Nineteen EC and 15 VC were enrolled from the natural virus controller cohort (NaViC). T-cell counts were monitored over years, the mean annual change was calculated and plasma concentrations of 25 cytokines were evaluated using a multiplex bead array.

RESULTS: While absolute numbers of T-cells did not differ between EC and VC over time, we observed a significant decrease of CD4+ T-cell percentages in VC but not in EC (median [interquartile range]: EC: 37% [28-41] vs. VC: 29% [25-34]; p=0.02). ECs had lower levels of macrophage inflammatory protein-1β (MIP-1β, p = 0.003), interferon γ-induced protein-10 (IP-10, p = 0.03) and monokine induced by interferon-γ (MIG, p = 0.02). CD4+ T-cell percentages inversely correlated with MIP 1-β (r = -0.42, p = 0.017) and IP-10 (r = -0.77, p< 0.0001) Conclusions: A subtle decline of CD4+ T-cell percentages could be observed in VC but not in EC, which was associated with higher plasma levels of proinflammatory cytokines. Hence, even low levels of HIV replication might go along with a progressive decline in CD4+ T-cell counts in LTNP.