CD4+ T cell evolution and predictors of its trend before and after tenofovir/didanosine backbone in the presence of sustained undetectable HIV plasma viral load.
BACKGROUND
Tenofovir with full-dose didanosine has been associated with paradoxical CD4 + T cell decrease despite virological suppression. We investigated whether tenofovir plus didanosine at a weight-adjusted dosage could be responsible for such an effect, and factors associated with CD4 + T cell count evolution under this combination.


METHODS
This was a prospective observational multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts). Patients with HIV plasma viral load suppression for >/= 6 months who switched to an antiretroviral combination including tenofovir plus didanosine were studied, as long as virological success was maintained. CD4 + T cell count variations over time (slopes) were compared before and after switching to tenofovir plus didanosine using linear mixed models and segmented regression analysis.


RESULTS
Annual time-weighted CD4 + T cell count slope did not change significantly after the prescription of tenofovir plus didanosine: it was 14 cells/mm(3) [95% confidence interval (CI) - 7 to 35] from month - 24 to month - 12, 12 cells/mm(3) (95% CI - 14 to 38) from month - 12 to the time of switching, 30 cells/mm(3) (95% CI 5-55) from switching to month + 12 and 15 cells/mm(3) (95% CI - 8 to 39) from month + 12 to month + 24 after switching to tenofovir plus didanosine. No significant change in the slope of the segment after the switch to tenofovir plus didanosine-containing regimens when compared with the segment preceding the intervention was found (CD4 + T cell count slope change: 24 cells/mm(3); 95% CI - 10 to 58). Similar results were obtained using CD4 + T cell percentage over total lymphocytes. The significant independent predictors of lower CD4 + T cell count slope were older age (P = 0.006), lower nadir CD4 + T cell count (P < 0.001) and positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated creatinine clearance was an additional independent predictor of lower CD4 + T cell count slope (P = 0.02), but only after excluding nadir CD4 + T cell count.


CONCLUSIONS
Tenofovir plus didanosine (weight-adjusted dosage) was not associated with paradoxical CD4 + T cell decrease in our patients maintaining undetectable HIV plasma viral load for a maximum of 24 months after switching. Several factors could explain variability in CD4 + T cell count evolution in these patients.
Torti
Carlo
C
Università degli Studi di Brescia, p le Spedali Civili 1, Brescia, Italy. torti.carlo@libero.it
Lapadula
Giuseppe
G
Barreiro
Pablo
P
Soriano
Vicente
V
Mandalia
Sundhiya
S
De Silvestri
Annalisa
A
Suter
Fredy
F
Maggiolo
Franco
F
Antinori
Andrea
A
Antonucci
Francesco
F
Maserati
Renato
R
El Hamad
Issa
I
Pierotti
Piera
P
Sighinolfi
Laura
L
Migliorino
Guglielmo
G
Ladisa
Nicoletta
N
Carosi
Giampiero
G
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000375:Aging / Q000502:physiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015331:Cohort Studies; D016049:Didanosine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012307:Risk Factors; D012727:Sex Characteristics; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine; D016049:Didanosine