Barcelona 2013
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| Abstract #366 - E-Posters English | ||||
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Session: 50.6: E-Posters English (Poster) on Sunday in Chaired by Authors: Presenting Author: Dr Irina Tcherepanova - Argos Therapeutics inc., United States |
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| Additional Authors: Dr. Jordi Casabona, Sra Cristina Sanclemente, Dra. Anna Esteve, Dra. Victoria Gonzalez, Grupo HIVITS TS, | ||||
| Aim: Strategies for HIV eradication will hinge on the ability to purge latently infected cells harboring HIV proviral DNA (pDNA). The levels of HIV pDNA in patients treated with ART and in the absence of other interventions are stable for years serving as a reservoir for re-emergence of HIV in the absence of ART therapy. Previously we reported results of a clinical study testing AGS-004 in chronically infected HIV patients. AGS-004 is an autologous immunotherapy consisting of dendritic cells electroporated with autologous PCR-amplified Gag, Vpr, Rev and Nef RNAs along with synthetically-derived CD40L RNA. Twenty-five subjects received four immunizations in combination with ART followed by an analytic treatment interruption (ATI). Subjects were able to receive two more doses of AGS-004 during the ATI according to pre-specified conditions in the clinical protocol. The primary endpoint was to assess the plasma viral load (VL) after 12 weeks of ATI compared to pre-treatment VL set point levels. Twenty-one subjects reached the primary endpoint. The average time to detectable VL after the start of ATI was 3.8 weeks and the time to peak VL was 8 weeks. After 3 months of drug interruption the average change in the new set point for all responders was -1.21 logs. In this study we evaluated the impact of AGS-004 on the HIV proviral reservoir in 20 evaluable patients from this trial. | ||||
| Method / Issue: The integrated HIV pDNA was measured by repetitive sampling Alu-Gag PCR using genomic DNA from purified CD4+ T cells. Samples at a baseline (week 0) and after four immunizations with AGS-004 (week 14) for this analysis were available from 20 of 21 subjects meeting the primary endpoint. Samples from 10 subjects were available after 10 weeks of ATI (week 24). | ||||
| Results / Comments: In the analysis of week 14 versus baseline, 5 of 20 (25%) measured subjects had an increase in pDNA levels, 8 subjects (40%) had stable levels and 7 subjects (35%) had decreased levels. Subjects with lower baseline levels of pDNA were more likely to experience a decrease in pDNA levels during treatment with AGS-004. In the analysis of week 24 samples (after ten weeks of ATI), 8 of 10 had increased pDNA levels which coincided with elevated plasma VL. This is consistent with other reports. However, in 2 of 10 subjects, pDNA levels continued to decline during ATI. This decline was associated with long term VL control in the absence of ART. | ||||
| Discussion: To our knowledge this is the first report of the HIV pDNA levels modulated in response to DC-based immune therapy. Thus the immune therapy such as AGS-004 is a good candidate for combination with ART and latency re-activating agents in pursuit of HIV eradication. | ||||
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