Journal Article

Relationship between HIV/Highly Active Antiretroviral Therapy (HAART)—associated Lipodystrophy Syndrome and Stavudine-Triphosphate Intracellular Levels in Patients with Stavudine-Based Antiretroviral Regimens

Pere Domingo, Maria Carmen Cabeza, Alain Pruvost, Juliana Salazar, Maria del Mar Gutierrez, Maria Gracia Mateo, Joan C. Domingo, Irene Fernandez, Francesc Villarroya, Jessica Muñoz, Francesc Vidal and Montserrat Baiget

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 7, pages 1033-1040
Published in print April 2010 | ISSN: 1058-4838
Published online April 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/651117
Relationship between HIV/Highly Active Antiretroviral Therapy (HAART)—associated Lipodystrophy Syndrome and Stavudine-Triphosphate Intracellular Levels in Patients with Stavudine-Based Antiretroviral Regimens

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Background

The link between human immunodeficiency virus/highly active antiretroviral therapy (HAART)—associated lipodystrophy syndrome (HALS) and the use of thymidine analogues has been well established. However, to our knowledge, no relationship has been proven between intracellular levels of stavudine (d4T) and HALS.

Methods

We measured peripheral blood mononuclear cell intracellular levels of d4T-triphosphate (TP) in patients who were receiving d4T as part of their antiretroviral regimens. d4T-TP levels were determined by a validated liquid chromatography-tandem mass spectrometry assay method. The diagnosis of HALS was made in accordance with the criteria of a lipodystrophy severity grading scale. The Student t test, Pearson correlations, 1-way analysis of variance with Bonferroni correction, and stepwise logistic regression were used for statistic analyses.

Results

This was a cross-sectional study. There were 33 patients: 17 with HALS and 16 without HALS. The median concentration of d4T-TP for patients with HALS was 20.60 femtomoles (fmol)/1 × 106 cells (interquartile range [IQR], 14.90–26.92 fmol/1 × 106 cells) and for patients without HALS was 13.85 fmol/1 × 106 cells (IQR, 8.65–20.15 fmol/1 × 106 cells) (P = .013). The median d4T-TP intracellular level in patients who had developed an AIDS-defining condition was 22.50 fmol/1 × 106 cells (IQR, 15.80–27.37 fmol/1 × 106 cells) and in those who had not was 14.40 fmol/1 × 106 cells (IQR, 10.80–20.40 fmol/1 × 106 cells) (P = .037). There were no statistically significant differences in d4T-TP intracellular levels with respect to the presence of metabolic syndrome, the clinical form of HALS (pure lipoatrophic vs mixed), the degree of facial lipoatrophy, the presence of hepatitis C virus infection, and the pair of nucleosides in HAART. d4T-TP levels correlated only with cumulative d4T exposure in time and dose. d4T-TP intracellular levels were independently associated with HALS (odds ratio, 1.58; 95% confidence interval, 1.08–2.32; P = .019).

Conclusions

Intracellular levels of d4T-TP are strongly associated with the development of HALS.

Journal Article.  5583 words. 

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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