HIV-1 viruses detected during episodic blips following interleukin-7 administration are similar to the viruses present before and after interleukin-7 therapy

Abstract

Background: Administration of recombinant human interleukin (IL)-7 leads to CD4 and CD8 T-cell expansions in HIV-infected individuals, demonstrating promising capacity for immune reconstitution. However, a proportion of patients treated with recombinant human IL-7 experience transient increases in plasma HIV-RNA (‘blips’), possibly reflecting ‘purging’ of a quiescent reservoir that provides a barrier to viral eradication. Objective: To identify the sources of HIV detected during transient viremic episodes following IL-7 administration, viral quasispecies were analyzed in a total of 281 primary sequences derived from seven patients who experienced the episodic blips following IL-7 therapy. Method: The C2-V3 regions of the HIV-1 env gene were sequenced from HIV-1 RNA in plasma and HIV DNA from peripheral blood mononuclear cells (PBMCs) obtained at baseline (day 0 of recombinant human IL-7 therapy), during the episode of viral blips (day 4), and at a time when levels of plasma HIV-RNA had returned to less than 50 copies/ml (day 28). Results: The HIV sequences detected during transient viremia following IL-7 administration were closely related to those of the plasma viruses present before and after cytokine administration. All virus quasispecies detected during blips were also present in proviral sequences in PBMCs. Conclusion: The low level viremia induced by IL-7 likely reflects predominantly transient induction or release of virus from a preexisting pool rather than activation of silent quasispecies.