Effects of the change from Stavudine to tenofovir in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy: studies on mitochondrial toxicity and thymic function.
BACKGROUND
Changing from drugs that have significant mitochondrial toxicity to less toxic compounds may be of benefit in human immunodeficiency virus (HIV)-positive patients who receive highly active antiretroviral therapy. Few data on mitochondrial toxicity of antiviral drugs are available in HIV-positive children.


METHODS
Eighteen HIV-positive children (median age, 10.9 years) receiving a stavudine-containing regimen were randomized to maintain stavudine (arm A) or change to tenofovir (arm B), while preserving the remaining drugs. Glucose, lipidic, and viro-immunologic factors were assessed at months 0, 1, 3, 6, 12, and 18. Thymic output and mtDNA content were measured in peripheral blood mononuclear cells at 0 and 6 months, mtDNA in isolated CD4+ and CD8+ T cells after 18 months.


RESULTS
From baseline to month 6, arms A and B showed similar thymic output and mtDNA. After 18 months, a significant decrease in plasma HDL was observed in arm B, along with a small increase in blood glucose; mtDNA showed no difference. In the 2 arms other factors did not show significant differences from the baseline and from the previous values at 18 months.


CONCLUSIONS
Changing from stavudine to tenofovir was well-tolerated, and viro-immunologic success was maintained.
Rosso
Raffaella
R
Infectious Diseases Clinics, San Martino Hospital, University of Genoa, Genoa, Italy.
Nasi
Milena
M
Di Biagio
Antonio
A
Repetto
Ernestina
E
Dentone
Chiara
C
Pinti
Marcello
M
Nemes
Elisa
E
Ferraresi
Roberta
R
Mussini
Cristina
C
Esposito
Roberto
R
Viscoli
Claudio
C
Cossarizza
Andrea
A
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001786:Blood Glucose; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D002648:Child; D004272:DNA, Mitochondrial / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D018119:Stavudine / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir; D013950:Thymus Gland / Q000502:physiology*; D019562:Viral Load
D019380:Anti-HIV Agents; D001786:Blood Glucose; D004272:DNA, Mitochondrial; D008055:Lipids; D063065:Organophosphonates; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine