Impact of Integrase Inhibition Compared With Nonnucleoside Inhibition on HIV Reservoirs in Lymphoid Tissues
| Autor: | Thomas Reimann, Jake S. Jasurda, Timothy W. Schacker, Krystelle Nganou-Makamdop, Meghan K Rothenberger, Jodi Anderson, Francis Ssali, Peter J. Southern, Katherine Perkey, Jeffrey G. Chipman, Cavan S. Reilly, Gregory J. Beilman, Erika S. Helgeson, Torfi Hoskuldsson, Hope Pearson, Caitlin David, Thomas E. Schmidt, Courtney V. Fletcher, Samuel P. Calisto, Ashley T. Haase, Cissy Kityo, Daniel C. Douek, Stephen W. Wietgrefe |
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| Přispěvatelé: | Global Health, Graduate School, AII - Infectious diseases, APH - Personalized Medicine, APH - Quality of Care |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Cyclopropanes Male animal structures Anti-HIV Agents Lymphoid Tissue Human immunodeficiency virus (HIV) Integrase inhibitor HIV Infections Viremia In situ hybridization 030312 virology antiviral effect medicine.disease_cause Young Adult 03 medical and health sciences Raltegravir Potassium Translational Research medicine Humans Pharmacology (medical) HIV Integrase Inhibitors In Situ Hybridization 0303 health sciences biology Follicular dendritic cells HIV Viral Load medicine.disease Raltegravir Antiretroviral therapy Virology Benzoxazines CD4 Lymphocyte Count 3. Good health Integrase Infectious Diseases virus decay Alkynes biology.protein Female Lymph Nodes pharmacology Dendritic Cells Follicular drug levels medicine.drug |
| Zdroj: | Journal of Acquired Immune Deficiency Syndromes (1999) Journal of acquired immune deficiency syndromes (1999), 81(3), 355-360. Lippincott Williams and Wilkins |
| ISSN: | 1525-4135 |
| DOI: | 10.1097/qai.0000000000002026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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