Cumulative exposure to ritonavir-boosted atazanavir is associated with cholelithiasis in patients with HIV-1 infection.

Abstract

OBJECTIVES:

This study aimed to examine the effect of long-term treatment with ritonavir-boosted atazanavir (atazanavir/ritonavir) on cholelithiasis.

METHODS:

A single-centre, cross-sectional study was conducted to elucidate the prevalence of cholelithiasis in patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Univariate and multivariate logistic regression analyses were applied to estimate the effects of >2 years of atazanavir/ritonavir exposure on cholelithiasis as the primary exposure.

RESULTS:

Of the 890 study patients, 84 (9.4%) had >2 years of atazanavir/ritonavir exposure. Cholelithiasis was twice as frequent in those treated for >2 years with atazanavir/ritonavir [15 (18%) of 84 patients] compared with those treated for <2 years [72 (8.9%) of 806 patients] (P = 0.018). Univariate analysis showed a significant association between >2 years of atazanavir/ritonavir exposure and cholelithiasis (OR = 2.216; 95% CI = 1.206-4.073; P = 0.010) and the association almost persisted in multivariate analysis (adjusted OR = 1.806; 95% CI = 0.922-3.537; P = 0.085). Long-term treatment (>2 years) with other commonly used protease inhibitors, such as ritonavir-boosted lopinavir and ritonavir-boosted darunavir, was not associated with cholelithiasis in univariate and multivariate analysis. Additional analysis showed that >1 year of exposure to atazanavir/ritonavir was significantly associated with cholelithiasis (OR = 1.857; 95% CI = 1.073-3.214; P = 0.027), whereas >1 year of exposure to ritonavir-boosted lopinavir and ritonavir-boosted darunavir was not.

CONCLUSIONS:

Long-term treatment of patients with HIV-1 infection for >2 years with atazanavir/ritonavir was associated with an increased risk of cholelithiasis compared with patients with shorter exposure. Long-term exposure to atazanavir/ritonavir appears to increase the risk of cholelithiasis in patients with HIV-1 infection.

• Authors: Takeshi Nishijima, Takuro Shimbo, Hirokazu Komatsu, Yohei Hamada, Hiroyuki Gatanaga, Yoshimi Kikuchi, Shinichi Oka
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 5 Pg. 1385-9 (May 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24379301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Oligopeptides
• Pyridines
• Atazanavir Sulfate
• Ritonavir

Topics

• Abdomen (diagnostic imaging)
• Adult
• Anti-HIV Agents (adverse effects, therapeutic use)
• Atazanavir Sulfate
• Cholelithiasis (chemically induced, epidemiology)
• Cross-Sectional Studies
• Female
• HIV Infections (complications, drug therapy, virology)
• HIV-1 (isolation & purification)
• Humans
• Male
• Oligopeptides (adverse effects, therapeutic use)
• Prevalence
• Pyridines (adverse effects, therapeutic use)
• Ritonavir (adverse effects, therapeutic use)
• Time Factors
• Ultrasonography