Rate of CD4+ cell count increase over periods of viral load suppression: relationship with the number of previous virological failures.
BACKGROUND
Although the kinetics of CD4(+) cell counts have been extensively studied in antiretroviral-naive HIV-infected patients, data on individuals who have failed combination antiretroviral therapy (cART) are lacking.


METHODS
This analysis was based on the ICONA Foundation Study. Subjects with > or = 1 episode of viral suppression after starting first-line cART were included (n = 3537). Following a viral rebound, patients who achieved another episode of viral suppression could reenter the analysis. The percentage of patients with an increase in CD4(+) cell count >300 cells/mm(3) was estimated using Kaplan-Meier techniques; the rate of CD4(+) cell count increase per year was estimated using a multivariable, multilevel linear model with fixed effects of intercept and slope. Multivariable models were also fitted to include several covariates.


RESULTS
The median time to reach a CD4(+) cell count increase >300 cells/mm(3) from baseline was significantly associated with the number of failed regimens: 34 months, 41 months, 51 months, and 45 months in subjects without evidence of previous virological failure, or 1, 2, or > or = 3 previous virologically failed regimens, respectively (P < .001, by log-rank test). The annual estimated increases in CD4(+) cell count were 36 cells/mm(3) (95% confidence interval [CI], 34-38 cells/mm(3)), 28 cells/mm(3) (95% CI, 11-21 cells/mm(3)), 31 cells/mm(3) (95% CI, 26-36 cells/mm(3)), and 26 cells/mm(3) (95% CI, 18-33 cells/mm(3)), respectively. Differences in the annual CD4(+) cell count increase were observed between specific antiretrovirals.


CONCLUSIONS
Subjects with > or = 1 virological failure took a longer time to reach a CD4(+) cell count >300 cell/mm(3) and had a slower annual increase than those without virological failure. Efforts should be made to optimize first-line cART, because this represents the best chance of achieving an effective CD4(+) response.
Trotta
Maria Paola
MP
Clinical Department, National Institute for Infectious Diseases L. Spallanzani, Roma, Italy. mariapaola.trotta@inmi.it
Cozzi-Lepri
Alessandro
A
Ammassari
Adriana
A
Vecchiet
Jacopo
J
Cassola
Giovanni
G
Caramello
Pietro
P
Vullo
Vincenzo
V
Soscia
Fabrizio
F
Chiodera
Alessandro
A
Ladisa
Nicoletta
N
Abeli
Clara
C
Cauda
Roberto
R
Buonuomi
Anna Rita
AR
Antinori
Andrea
A
d'Arminio Monforte
Antonella
A
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents