Possible mechanism of toxicity of zidovudine by induction of apoptosis of CD4+ and CD8+ T-cells in vivo.
Some HIV-infected patients have a discordant response to highly active antiretroviral therapy with a low virus load and an incomplete restoration of CD4+ T-cell counts. Zidovudine may limit CD4+ restoration by a hematotoxic mechanism. Apoptosis and T-cell counts were assessed in two patients before and after they switched from zidovudine to stavudine. Whereas CD4+ T-cell apoptosis fell from 52% and 66% before the zidovudine switch to 7% and 12%, respectively, after the switch, the patients' CD4+ counts rose gradually to +183 and +150 cells, respectively. It was therefore hypothesized that zidovudine directly induced apoptosis. Zidovudine withdrawal could be tested before immunological interventions such as interleukin-2 therapy are considered.
Benveniste
O
O
Service des Maladies Infectieuses et Tropicales, Hĵpital Bichat-Claude Bernard, Paris, France. olivier.benveniste@psl.ap-hop-paris.fr
Estaquier
J
J
Lelièvre
J D
JD
Vildé
J L
JL
Ameisen
J C
JC
Leport
C
C
D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015215:Zidovudine / Q000009:adverse effects*
D019380:Anti-HIV Agents; D015215:Zidovudine