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Session 104 Poster Abstracts
Systemic and Organ Complications of HIV-1 and Antiretroviral Therapies
Monday, 1:30 - 3:30 pm
Poster Hall


749    
Unexpected CD4 Cell-count Decline in Patients Receiving Didanosine- and Tenofovir-based Regimens Despite Undetectable Viral Load
E Negredo*1, J Moltó1, D Burger2, P Viciana3, E Ribera4, J Puig1, R Paredes1, L Ruiz1, A Pruvost5, J Grassi5, and B Clotet1
1Lluita contra la SIDA Fndn. and “Irsicaixa” Fndn., Germans Trias i Pujol Hosp., Barcelona, Spain; 2Nijmegen Univ. Hosp., The Netherlands; 3Virgen del Rocio Univ. Hosp., Seville, Spain; 4Vall d’Hebron Hosp., Barcelona, Spain; and 5CEA Pharmacology and Immunology Unit, Saclay, France

Background:  We recently observed a significant CD4 cell count decline in  patients receiving didanosine (ddI) 400 mg,  tenofovir (TDF), and nevirapine, despite virological suppression.

Methods:  We identified from our database subjects who initiated combinations containing ddI or TDF for reasons other than virological failure, including simplification or intolerance. Changes in total, CD4+ and CD8+ lymphocyte counts since the initiation of therapy were analyzed retrospectively. Plasma concentration of ddI  was prospectively determined in 8 of these patients receiving ddI 400 mg+TDF+NVP and 3 weeks after a ddI dosage reduction.

Results:  A total of 302 patients were studied. A significant decrease in CD4 and CD8 and in total lymphocyte counts was seen only in subjects receiving  ddI standard dose +TDF-containing regimens, despite the maintenance of viral suppression. More than 50% of these patients showed a decline of more than 100 CD4 cells at 48 weeks. In contrast, subjects not receiving ddI+TDF together experienced the expected progressive increase in CD4 T cell counts. Plasma levels of ddI were elevated in all patients receiving standard ddI dose +TDF. DdI levels significantly decreased when patients weighting >60 kg reduced ddI dose to 250 mg, achieving similar levels to those generated by ddI 400 mg without TDF.

Conclusions:  Co-administration of ddI at standard doses plus TDF appears to exert a deleterious effect on CD4 and CD8 counts. Although lymphocyte toxicity related to excessive ddI plasma levels could explain our findings, other mechanisms cannot be excluded. Pharmacokinetic data suggest ddI dose reduction when coadministered with TDF.

Keywords: CD4 cell decline; Didanosine; Tenofovir