Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters.
Although continuous highly active antiretroviral therapy (HAART) is effective for many HIV-infected patients, it can be toxic and prohibitive in cost. By decreasing the total amount of time patients receive medications, intermittent HAART could reduce toxicity and cost. Therefore, we initiated a pilot study in which 10 HIV-infected individuals receiving effective therapy that resulted in levels of HIV RNA <50 copies per ml of plasma and CD4(+) T cell counts >300 cells per mm(3) of whole blood received repeated cycles of 7 days on HAART followed by 7 days off of HAART. Patients maintained suppression of plasma viremia for 32-68 weeks. There was no significant increase in HIV proviral DNA or replication-competent HIV in peripheral CD4(+) T cells or HIV RNA in peripheral blood or lymph node mononuclear cells. There was no significant change in CD4(+) T cell counts, no significant increase in CD4(+) or CD8(+) T cells expressing activation markers or producing IFN-gamma in response to HIV, no increase in CD4(+) T cell proliferation to p24 antigen, and no evidence for the development of resistance to HAART medications. There was a significant decrease in serum cholesterol and triglyceride levels. Thus, in this proof-of-concept study, short-cycle intermittent HAART maintained suppression of plasma viremia as well as HIV replication in reservoir sites while preserving CD4(+) T cell counts. In addition, there was a decrease in serum cholesterol and triglyceride levels. Intermittent therapy may be an important strategy to reduce cost and toxicity for HIV-infected individuals.
Dybul
M
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mdybul@nih.gov
Chun
T W
TW
Yoder
C
C
Hidalgo
B
B
Belson
M
M
Hertogs
K
K
Larder
B
B
Dewar
R L
RL
Fox
C H
CH
Hallahan
C W
CW
Justement
J S
JS
Migueles
S A
SA
Metcalf
J A
JA
Davey
R T
RT
Daucher
M
M
Pandya
P
P
Baseler
M
M
Ward
D J
DJ
Fauci
A S
AS
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D010865:Pilot Projects; D012367:RNA, Viral
D019380:Anti-HIV Agents; D012367:RNA, Viral