Standard vaccines increase HIV-1 transcription during antiretroviral therapy
AIDS
Authors: Yek, Christina; Gianella, Sara; Plana, Montserrat; Castro, Pedro; Scheffler, Konrad; Garcia, Felipe; Massanella, Marta; Smith, Davey M.
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. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Using Elecsys (R) HIV Combi PT assay to identify acute and early HIV infection in a teaching hospital of southwest China
INTERNATIONAL JOURNAL OF STD & AIDS
Authors: Zhu, Siyuan; Li, Dongdong; An, Jingna; Chen, Qixia; Liu, Qianqian; Tao, Chuanmin
Abstract
This study is the first attempt to evaluate the use of the Elecsys (R) HIV combi PT assay in identifying acute and early HIV infection in southwest China. We also analyzed the extent of cutoff ratios overlap between false-positive and true-positive results to aid the identification of HIV infection, using samples from the West China Hospital in Chengdu, Sichuan Province from April 2012 to December 2013. Reactive results from a screening test were retested and all repeatedly reactive samples - if available - were confirmed with Western blot, HIV-1 p24 antigen, or HIV-1 RNA. Of 241,840 samples screened, the Elecsys (R) HIV combi PT assay identified 54 patients with acute and early HIV infection; 99.8% cases with cutoff index ratios 50 were proved to be true-positive HIV infection and 95.6% cases with cutoff index ratios <15 were falsely positive. In conclusion, the Elecsys (R) HIV combi PT assay can identify acute and early HIV infection, including those who might have been missed by third-generation HIV screening assays and Western blot. However, cutoff index ratios <15 are not always false-reactive results; a definitive result cannot be attained without further confirmation. In resource-poor regions where a HIV-1 nucleic acid test may be unaffordable, detection of HIV-1 p24 antigen can be an alternative strategy to diagnose HIV infection in individuals with a negative or indeterminate Western blot.