Impact of Integrase Inhibition Compared with Nonnucleoside Inhibition on HIV Reservoirs in Lymphoid Tissues

Meghan Rothenberger, Krystelle Nganou-Makamdop, Cissy Kityo, Francis Ssali, Jeffrey G. Chipman, Gregory J. Beilman, Torfi Hoskuldsson, Jodi Anderson, Jake Jasurda, Thomas E. Schmidt, Samuel P. Calisto, Hope Pearson, Thomas Reimann, Caitlin David, Katherine Perkey, Peter Southern, Steve Wietgrefe, Erika Helgeson, Cavan Reilly, Ashley T. HaaseDaniel C. Douek, Courtney V. Fletcher, Timothy W. Schacker

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background:HIV is produced in lymphoid tissues (LT) and stored on the follicular dendritic cell network in LT. When antiretroviral therapy is started, plasma viremia decays in 2 phases; the first within days of starting therapy and the second over weeks. Raltegravir (RAL), an integrase inhibitor, has been associated with only a single rapid phase of decay, and we speculated this may be due to higher intracellular concentration (IC) of RAL in LT. We have previously measured suboptimal ICs of antiretroviral therapy agents in LT, which were associated with slower decay of both vRNA+ cells and the follicular dendritic cell network pool.Setting:Outpatient clinic at the Joint Clinical Research Center in Kampala, Uganda.Methods:We compared the rate of decay in LT in people starting RAL with those starting efavirenz (EFV).Results:There was no difference in the rate of virus decay in LT. The ratio of the ICs of RAL and EFV in lymph node to the concentration of drug that inhibits 95% of virus in blood was 1 log lower in lymph node for EFV and >3 logs lower for RAL.Conclusion:These data further highlight the challenges of drug delivery to LT in HIV infection and demonstrate that RAL is not superior to EFV as judged by direct measurements of the source of virus in LT.

Original languageEnglish (US)
Pages (from-to)355-360
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume81
Issue number3
DOIs
StatePublished - Jul 1 2019

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Keywords

  • HIV
  • antiviral effect
  • drug levels
  • pharmacology
  • virus decay

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Rothenberger, M., Nganou-Makamdop, K., Kityo, C., Ssali, F., Chipman, J. G., Beilman, G. J., Hoskuldsson, T., Anderson, J., Jasurda, J., Schmidt, T. E., Calisto, S. P., Pearson, H., Reimann, T., David, C., Perkey, K., Southern, P., Wietgrefe, S., Helgeson, E., Reilly, C., ... Schacker, T. W. (2019). Impact of Integrase Inhibition Compared with Nonnucleoside Inhibition on HIV Reservoirs in Lymphoid Tissues. Journal of Acquired Immune Deficiency Syndromes, 81(3), 355-360. https://doi.org/10.1097/QAI.0000000000002026