JAC Advance Access originally published online on November 11, 2008
Journal of Antimicrobial Chemotherapy 2009 63(1):184-188; doi:10.1093/jac/dkn461
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Original research |
Influence of repeated cycles of structured therapy interruption on the rate of recovery of CD4+ T cells after highly active antiretroviral therapy resumption
1 Infectious Diseases Department, Hospital Clinic of Barcelona, Villarroel 170, 08036 Barcelona, Spain 2 Immunology Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain 3 Laboratory of Retrovirology and Viral Immunopathology, Hospital Clinic of Barcelona, 08036 Barcelona, Spain
Received 9 June 2008; returned 8 July 2008; revised 30 September 2008; accepted 12 October 2008
* Corresponding author. Tel: +34-93-2275586; Fax: +34-93-4514438; E-mail: aleon{at}clinic.ub.es
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).
Conclusion: 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.
Keywords: STI , HAART , CD4+ T cell recovery