IL-1beta (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART) against lipodystrophic syndrome.
OBJECTIVE
To evaluate the impact of acquired and inherited factors on the development of lipodystrophic syndrome in patients on highly active antiretroviral therapy.


METHODS
Two hundred forty-three human immunodeficiency virus-infected Caucasians on highly active antiretroviral therapy were prospectively followed-up for 3 years. Eleven were naIve and 232 were on antiretrovirals (mean, 93.0 months +/- 43.8 months). Lipodystrophic syndrome was diagnosed clinically with a lipodystrophy severity grading scale. Polymorphisms of cytokines (IL-1beta, IL-6, TNF-alpha), TLR4, and NOS genes were genotyped.


RESULTS
Ninety (37%) patients developed lipodystrophic syndrome. The polymorphic T allele of the (+3954C/T) polymorphism of IL-1beta was less frequent in patients with lipodystrophic syndrome compared with those without (17.8% vs. 27.0%, P = 0.03). Factors significantly associated with lipodystrophic syndrome were time on stavudine (P < 0.001), use of stavudine (P = 0.001), absence of the T allele of the (+3954C/T) IL-1beta polymorphism (P = 0.02), acquired immune deficiency syndrome diagnosis (P = 0.005), nadir levels of CD4 (P = 0.003), and time on highly active antiretroviral therapy (P = 0.003). Of these factors, only the time on stavudine (hazard ratio [95% confidence intervals] 1.007 [1.001-1.013]), use of stavudine (1.678 [1.048-2.68]), and absence of the T allele of the IL-1beta (+3954C/T) polymorphism (0.569 [0.347-0.931]) were significantly associated with lipodystrophic syndrome by Cox regression.


CONCLUSIONS
Genotyping of the (+3954C/T) polymorphism of IL-1beta could be useful in patients starting highly active antiretroviral therapy, especially in potential users of stavudine, to predict their risk of developing lipodystrophic syndrome.
Asensi
Victor
V
Infectious Diseases and Molecular Genetics Sections, Hospital Central de Asturias, Oviedo, Spain.
Rego
Carolina
C
Montes
A Hugo
AH
Collazos
Julio
J
Carton
José A
JA
Castro
Mónica G
MG
Alvarez
Victoria
V
Fernández
Cristina
C
Maradona
José A
JA
Valle-Garay
Eulalia
E
D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D017931:DNA Primers; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008060:Lipodystrophy / Q000235:genetics* / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D017931:DNA Primers; D053583:Interleukin-1beta