JAC Advance Access published online on April 13, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm100
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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
1 Università degli Studi di Brescia, p.le Spedali Civili 1, 25123 Brescia, Italy 2 Carlos III Hospital, c. Sinesio Delgado 10 28029, Madrid, Spain 3 Chelsea-Westmister Hospital, 369 Fulham Road, London SW10, UK 4 Policlinico S. Matteo, p.le Camillo Golgi 2, 27100 Pavia, Italy 5 Ospedali Riuniti di Bergamo, largo Barozzi 1, 24128 Bergamo, Italy 6 INMI L. Spallanzani, via Portuense 292, 00149 Roma, Italy 7 Ospedale S.M. Annunziata, via dell'Antella 52, 50011 Firenze, Italy 8 Azienda Ospedaliera S. Anna, corso Giovecca, 203 44100 Ferrara, Italy 9 Ospedale di Circolo, via A. Da Brescia 1, 21052 Busto Arsizio, Italy 10 Policlinico di Bari, p.za Giulio Cesare 11, 25124 Bari, Italy
Received 22 November 2006; returned 16 January 2007; revised 8 February 2007; accepted 13 March 2007
* Corresponding author. Tel: +39-030-3996624; Fax: +39-030-303061; E-mail: torti.carlo{at}libero.it
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/mm3 [95% confidence interval (CI) –7 to 35] from month –24 to month –12, 12 cells/mm3 (95% CI –14 to 38) from month –12 to the time of switching, 30 cells/mm3 (95% CI 5–55) from switching to month +12 and 15 cells/mm3 (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/mm3; 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.
Key Words: immune recovery , CD4 cell count , immune toxicity , antiretroviral therapy