Intermittent antiretroviral therapy in patients with controlled HIV infection.
BACKGROUND
To assess the safety of a drug-sparing treatment regimen in patients with high CD4 cell counts and controlled HIV replication under antiretroviral therapy.


METHODS
An open-label, non-inferiority study involving 403 adults with CD4 cell counts of 450 x 10(6) cells/l or greater and plasma HIV-1-RNA levels less than 200 copies/ml, randomly assigned to switch to an 8-week off, 8-week on regimen or to continue their antiretroviral regimen. The primary endpoint was the proportion of patients reaching a confirmed CD4 cell count less than 300 x 10(6) cells/l.


RESULTS
Over 96 weeks, the proportion of patients meeting this endpoint was non-inferior in the intermittent group (3.6 versus 1.5%, upper bound of the 95% confidence interval of the difference 5.6%). No AIDS-defining event and two non-HIV-related deaths (intermittent arm) were recorded. The median decrease from baseline in the CD4 cell count was greater in the intermittent arm (-155 versus -8 x 10(6) cells/l, P < 0.0001). Minor HIV-related events, mainly lymphadenopathy and mucosal candidiasis, were more frequent in the intermittent group (14 versus 7%, P = 0.04) as were thrombocytopenia. The incidence of grade 3-4 non-HIV-related events and laboratory abnormalities were not statistically different between the groups. At week 96, the proportion of patients with plasma HIV-1-RNA levels less than 400 copies/ml were 81 and 90% in the intermittent (8 weeks after treatment resumption) and continuous groups (P = 0.02), respectively, with similar patterns of HIV resistance genotypes.


CONCLUSIONS
Despite some limitations, an 8-week off and on intermittent treatment regimen appeared clinically safe over 96 weeks while sparing half of the drug exposure.
Marchou
Bruno
B
Hôpital Purpan, Toulouse, France. marchou.b@chu-toulouse.fr
Tangre
Philippe
P
Charreau
Isabelle
I
Izopet
Jacques
J
Girard
Pierre-Marie
PM
May
Thierry
T
Ragnaud
Jean-Marie
JM
Aboulker
Jean-Pierre
JP
Molina
Jean-Michel
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents