Reconstitution of thymic function in HIV-1 patients treated with highly active antiretroviral therapy.
The extent to which highly active antiretroviral therapy can restore thymic function in HIV-1 infected patients is not known. We simulate treatment using a temporal model of thymopoiesis during HIV-1 infection, tracking thymic function by the number of recent thymic emigrants (RTE) exported to the periphery per day. Our results suggest that suppressing viral load in peripheral blood and improving inherent thymic function are necessary for the reconstitution of RTE levels in adult thymic infection with either R5 or X4 HIV-1 strains. This is also the case in pediatric thymic infection with R5 strains. However, recovery of RTE levels during pediatric infection with X4 strains also depends on high drug efficacy within the thymus. We further predict that protease inhibitors have high levels of efficacy directly suppressing viral replication within the thymus, while reverse transcriptase inhibitors have low efficacy.
Ye
Ping
P
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kourtis
Athena P
AP
Kirschner
Denise E
DE
D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008954:Models, Biological; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors