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Standard vaccines increase HIV-1 transcription during antiretroviral therapy.

Standard vaccines increase HIV-1 transcription during antiretroviral therapy.
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Yek C, Gianella S, Plana M, Castro P, Scheffler K, García F, Massanella M, Smith DM,


Yek C, Gianella S, Plana M, Castro P, Scheffler K, García F, Massanella M, Smith DM, (click to view)

Yek C, Gianella S, Plana M, Castro P, Scheffler K, García F, Massanella M, Smith DM,

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AIDS (London, England) 30(15) 2289-98 doi 10.1097/QAD.0000000000001201

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.

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