Long-cycle structured intermittent versus continuous highly active antiretroviral therapy for the treatment of chronic infection with human immunodeficiency virus: effects on drug toxicity and on immunologic and virologic parameters.
We evaluated the effect of long-cycle structured intermittent therapy (SIT; 4 weeks without highly active antiretroviral therapy [HAART] followed by 8 weeks with HAART) versus continuous HAART. The study was prematurely terminated to new enrollment because of the emergence of genetic mutations associated with resistance to antiretroviral drugs in 5 patients. After 48 weeks, there was no significant difference between groups in lipid, hepatic transaminase, and C-reactive protein levels in 41 patients. Although there were no differences in CD4(+) or CD8(+) T cell counts or the percentage of cells that were CD4(+)CD25(+), CD8(+)CD25(+), or CD4(+)DR(+), patients who received SIT had a significantly higher percentage of CD8(+)CD38(+) and CD8(+)DR(+) cells. There was no clear autoimmunization effect by immunologic or virologic parameters. There was no benefit to long-cycle SIT versus continuous HAART with regard to certain toxicity, immunologic, or virologic parameters.
Dybul
Mark
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. mdybul@nih.gov.
Nies-Kraske
Elizabeth
E
Daucher
Marybeth
M
Hertogs
Kurt
K
Hallahan
Claire W
CW
Csako
Gyorgy
G
Yoder
Christian
C
Ehler
Linda
L
Sklar
Peter A
PA
Belson
Michael
M
Hidalgo
Bertha
B
Metcalf
Julia A
JA
Davey
Richard T
RT
Rock Kress
Diane M
DM
Powers
April
A
Fauci
Anthony S
AS
D000410:Alanine Transaminase / Q000097:blood; D000626:Aminopeptidases / Q000097:blood; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002097:C-Reactive Protein / Q000032:analysis; D016516:CD4-CD8 Ratio; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005500:Follow-Up Studies; D043384:Glutamyl Aminopeptidase; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008055:Lipids / Q000097:blood; D018655:Lymphocyte Count; D012367:RNA, Viral / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D008055:Lipids; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D002097:C-Reactive Protein; D000410:Alanine Transaminase; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase