Influence of repeated cycles of structured therapy interruption on the rate of recovery of CD4+ T cells after highly active antiretroviral therapy resumption.
BACKGROUND
CD4+ T cell recovery dynamics were analysed during the 'on treatment' periods in structured therapy interruption (STI) as well as the long-term immune reconstitution with highly active antiretroviral therapy (HAART) after finishing STI.


METHODS
One hundred and twenty HIV-1-infected patients on successful HAART were randomized to receive for 2 years continuous HAART (n=37) or two different strategies of STI (n=83). After this period, most patients received continuous HAART for 2 years.


RESULTS
During the STI period, the rate of recovery of CD4+ T cells decreased progressively from the first to the last resumption of HAART {median change of increase: +232 [interquartile range (IQR): +126, +318], +116 (IQR: +10, +471), +87 (IQR: -54, +252) and -26 (IQR: -352, +211) cells/mm3 after the first, second, third and fourth resumption, respectively}. After the STI period and 2 years of continuous HAART, the median CD4+ count remained significantly lower than at baseline in STI arms, both in the virological arm [559 (IQR: 383, 727) versus 771 (IQR: 625, 913) cells/mm3, P<0.0001] and the immunological arm [619 (IQR: 501, 789) versus 787 (IQR: 657, 954) cells/mm3, P<0.0001], but not in the control arm [886 (IQR: 564, 1122) versus 780 (IQR: 539, 945) cells/mm3, P=0.68]. In a multivariate analysis, the nadir of CD4+ T cells and the baseline value of CD4+ before the STI period independently predicted the level of CD4+ T cells 2 years after resumption of HAART (in both cases, P<0.0001).


CONCLUSIONS
The drop in CD4+ cell count after a first and a second period of 3 months of interruption of HAART was completely recovered after resuming HAART; conversely, interruptions longer than 6 months were deleterious for the recovery of CD4+. CD4+ cell count did not rebound completely in patients who received 2 years of HAART after 2 years of STIs.
León
Agathe
A
Infectious Diseases Department, Hospital Clinic of Barcelona, Villarroel 170, 08036 Barcelona, Spain. aleon@clinic.ub.es
Martinez
Esteban
E
Milinkovic
Ana
A
Mora
Borja
B
Mallolas
Josep
J
Blanco
Jose L
JL
Larrousse
María
M
Laguno
Montserrat
M
Gallart
Teresa
T
Plana
Montserrat
M
Gatell
José M
JM
Garcia
Felipe
F
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D028761:Withholding Treatment
D019380:Anti-HIV Agents