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PERSISTENT DETECTION OF HIV RNA+ CELLS WITH ART STARTED IN FIEBIG 1&2 VS FIEBIG 3-5
Eugène Kroon1, Mark de Souza1, Suthat Chottanapund1, Jodi Anderson2, Sopark Manasnayakorn3, Siri Jorstad2, Caitlin David2, Adam Conner2, Erika Helgeson2, Cavan Reilly2, Merlin L. Robb4, Daniel Douek5, Jintanat Ananworanich4, Timothy Schacker2
1Thai Red Cross AIDS Research Center, Bangkok, Thailand,2University of Minnesota, Minneapolis, MN, USA,3Chulalongkorn University, Bangkok, Thailand,4US Military HIV Research Program, Silver Spring, MD, USA,5NIH, Bethesda, MD, USA
The reservoir of HIV DNA+ cells is stable during treatment of chronic HIV infection; however, it is unknown if treatment during acute HIV infection (AHI) will limit reservoir size or the pathology of virus replication in lymph nodes (LN).
We obtained LNs from 2 groups enrolled into the RV254 study; 55 individuals sampled during AHI and 31 identified in acute infection but were sampled after a mean of 348 days of ART (range 269 – 849 days, Table). We analyzed LNs by in situ hybridization (ISH) to determine the frequency of viral RNA (vRNA+) and DNA (vDNA+) cells and by immunohistochemistry (IHC) to determine the extent of LN fibrosis as a marker of inflammatory damage.
Prior to ART, the mean frequency of vRNA+ and vDNA+ cells was 2.3 x 10...5 cells/g LN (interquartile range 7.6 x 10...4 - 4.1 x 10...5) and 5.4 x 10...5 cells/g LN (interquartile range 2.3 x 10...5 – 1.5 x 10...6), respectively with no significant effect of Fiebig stage at the time of diagnosis. In the group receiving ART, the mean frequency of detection of vRNA+ and vDNA+ cells was 0.0 cells/g (interquartile range 0, 4.7 x 10...4) and 3.0 x 10...5 cells/g (interquartile range 1.6 x 10...5- 7.3 x 10...5), respectively. However, 15/31 (48%) LNs did have vRNA+ detectable cells (mean 9.1 x 10...4 cells/g, range 2.2 x 10...3 – 2.4 x 10...5 cells/g) and people initiating ART in F1 or F2 were significantly more likely to have vRNA+ cells (adjusted O.R. 6.48, p = 0.0354). There was no significant difference in vDNA+ cells/g in the group sampled during AHI or the group receiving ART. Significant collagen deposition into the parafollicular T cell zone (TZ) began as early as F1 and did not decay as a result of ART, however there was no significant increase over time.
We found that the of reservoir of vDNA+ cells was established as early as F1 and did not decay with ART. Further, inflammatory damage occurred (as measured by TZ collagen) as early as F1 and did not appear to decrease if ART was started in acute infection, however it did not progress. Finally, the detection of persistent vRNA production in LNs in people treated very early suggests that interventions to both block viral replication and elicit immune clearance of infected cells in LNs will be important.