Standard vaccines increase HIV-1 transcription during antiretroviral therapy
C Yek, S Gianella, M Plana, P Castro, K Scheffler… - Aids, 2016 - journals.lww.com
Aids, 2016•journals.lww.com
Objectives: Curative strategies using agents to perturb the HIV reservoir have demonstrated
only modest activity, whereas increases in viremia after standard vaccination have been
described. We investigated whether vaccination against non-HIV pathogens can induce HIV
transcription and thereby play a role in future eradication strategies. Design: A randomized
controlled trial (NCT00329251) was performed to compare the effects of clinical vaccines
with placebo on HIV transcription and immune activation. Methods: Twenty-six HIV-infected …
only modest activity, whereas increases in viremia after standard vaccination have been
described. We investigated whether vaccination against non-HIV pathogens can induce HIV
transcription and thereby play a role in future eradication strategies. Design: A randomized
controlled trial (NCT00329251) was performed to compare the effects of clinical vaccines
with placebo on HIV transcription and immune activation. Methods: Twenty-six HIV-infected …
Abstract
Objectives:
Curative strategies using agents to perturb the HIV reservoir have demonstrated only modest activity, whereas increases in viremia after standard vaccination have been described. We investigated whether vaccination against non-HIV pathogens can induce HIV transcription and thereby play a role in future eradication strategies.
Design:
A randomized controlled trial (NCT00329251) was performed to compare the effects of clinical vaccines with placebo on HIV transcription and immune activation.
Methods:
Twenty-six HIV-infected individuals on suppressive antiretroviral therapy were randomized to receive a vaccination schedule (n= 13) or placebo (n= 13). Cell-associated RNA and DNA were extracted from peripheral blood mononuclear cells, and HIV was quantified by droplet digital PCR using primers for gag and 2-LTR (for HIV DNA), unspliced gag RNA (gag usRNA), multispliced tat-rev RNA (tat-rev msRNA) and polyA mRNA.
Results:
Significant increases in gag usRNA after influenza/hepatitis B vaccination (P= 0.02) and in gag usRNA (P= 0.04) and polyA mRNA (P= 0.04) after pneumococcus/hepatitis B vaccination were seen in vaccinees but not controls. HIV DNA and plasma HIV RNA did not change in either group. Increases in CD4+ and CD8+ T-cell activation markers (P= 0.08 and P< 0.001, respectively) and HIV-specific CD8+ responses (P= 0.04 for p24 gag, P= 0.01 for p17 gag and P= 0.04 for total gag) were seen in vaccinees but not controls.
Conclusion:
In this study, vaccination was associated with increases in HIV cell-associated RNA and HIV-specific responses during antiretroviral therapy. Using standard vaccines to stimulate HIV transcription may therefore be a useful component of future eradication strategies.
Lippincott Williams & Wilkins