A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection.
BACKGROUND
We previously demonstrated that short-cycle structured intermittent therapy (SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum levels of lipids. Adherence to such a regimen may be problematic for certain patients.


METHODS
Eight patients with a history of receiving combination ART that maintained suppression of plasma HIV RNA to <50 copies/mL received a once-daily SIT regimen of didanosine, lamivudine, and efavirenz.


RESULTS
For 7 patients, suppression of plasma HIV RNA to <50 copies/mL was maintained for 60-84 weeks. Four patients with adequate samples had no evidence for an increase in plasma viremia for up to 72 weeks, by use of an assay with a limit of detection of <1 copy/mL. The lack of rebound viremia may be the result of the persistence of efavirenz in plasma on day 7 of the no-therapy period, as was detected in 7 of 7 patients. There was no significant change in CD4(+) T cell counts or serum hepatic transaminase or lipid levels.


CONCLUSIONS
A once-daily short-cycle SIT regimen maintained suppression of plasma HIV RNA while preserving CD4(+) T cell counts. Such a regimen may have importance in resource-limited settings where the monetary cost of continuous ART is prohibitive.
Dybul
Mark
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland 20892, USA. dybulmr@nih.gov.
Nies-Kraske
Elizabeth
E
Dewar
Robin
R
Maldarelli
Frank
F
Hallahan
Claire W
CW
Daucher
Marybeth
M
Piscitelli
Stephen C
SC
Ehler
Linda
L
Weigand
Ann
A
Palmer
Sarah
S
Metcalf
Julia A
JA
Davey
Richard T
RT
Rock Kress
Diane M
DM
Powers
April
A
Beck
Ingrid
I
Frenkel
Lisa
L
Baseler
Michael
M
Coffin
John
J
Fauci
Anthony S
AS
D000410:Alanine Transaminase / Q000097:blood; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D048588:Benzoxazines; D002784:Cholesterol / Q000097:blood; D003521:Cyclopropanes; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D016049:Didanosine / Q000008:administration & dosage* / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000097:blood; D010078:Oxazines / Q000008:administration & dosage* / Q000097:blood; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D014280:Triglycerides / Q000097:blood
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004279:DNA, Viral; D010078:Oxazines; D012367:RNA, Viral; D014280:Triglycerides; D019259:Lamivudine; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C098320:efavirenz; D016049:Didanosine