Suboptimal CD4 gains in HIV-infected patients receiving didanosine plus tenofovir.
The combination of nucleos(t)ide analogues (NAs) is essential for the design of effective antiretroviral regimens. Although there are currently many options for the selection of such drug backbones, not all combinations display optimal results. As the number of these compounds has increased, it has become clear that the concomitant administration of certain NAs should be avoided due to high rates of toxicity and/or greater risk of virological failure. As an example, the combination of didanosine and tenofovir has recently been associated with a paradoxical depletion of CD4+ T cells in the face of complete viral suppression. Interference between the pathways leading to the intracellular activation of didanosine and tenofovir, and their blocking of the purine nucleoside phosphorylase, seems to explain this phenomenon.
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Pablo
P
Barreiro
Vincent
V
Soriano
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D011683:Purine-Nucleoside Phosphorylase; D000225:Adenine; D016049:Didanosine