Skip to main content
Close
Publication

Partial immunological and mitochondrial recovery after reducing didanosine doses in patients on didanosine and tenofovir-based regimens.

See all publications

Background: Tenofovir disoproxil fumarate (TDF) has a safe toxicity profile; however, administration together with didanosine (ddl) increases ddl levels causing mitochondrial damage and CD4+ T-cell decline. We assessed whether a simple reduction of the ddl dose in patients receiving ddl (400 mg/day) and TDF could revert this side effect.

Methods: Immunological and mitochondrial changes were analysed in 20 patients at baseline, after 14 months of receiving ddl (400 mg/day), TDF (300 mg/day) and nevirapine (NVP; 400 mg/day) and 14 months after a ddl dose reduction to 250 mg/day. Immunological analyses measured CD4+ and CD8+ T-cell counts and mitochondrial studies in peripheral blood mononuclear cells assessed mitochondrial DNA content by quantitative real-time PCR, cytochrome c oxidase (COX) activity by spectrophotometry and mitochondrial protein synthesis (COX-II versus beta-actin or COX-IV expression) by western blot.

Results: Treatment with TDF, ddl (400 mg/day) and NVP for 14 months produced significant decreases in mitochondrial parameters and CD4+ T-cell counts. The reduction in ddl dose resulted in mitochondrial DNA recovery; however, the remaining mitochondrial parameters remained significantly decreased. Levels of CD4+ T-cells were partially restored in 35% of patients. Subjects presenting a significant reduction in CD4+ T-cells during the high ddl dose period showed greater mitochondrial impairment in this stage and better mitochondrial and immunological recovery after drug reduction.

Conclusion: Treatment with TDF, ddl (400 mg/day) and NVP for 14 months produced significant decreases in mitochondrial parameters and CD4+ T-cell counts. The reduction in ddl dose resulted in mitochondrial DNA recovery; however, the remaining mitochondrial parameters remained significantly decreased. Levels of CD4+ T-cells were partially restored in 35% of patients. Subjects presenting a significant reduction in CD4+ T-cells during the high ddl dose period showed greater mitochondrial impairment in this stage and better mitochondrial and immunological recovery after drug reduction.

Not available in
This is not available in . You can go to the translated versions in these languages: