Urolithiasis in a Patient with HIV Receiving Atazanavir

Case in Point Urolithiasis in a Patient With HIV Receiving Atazanavir

Roula Baroudi, MD; David Posnick, DO; and Marquetta Flaugher, DSN, ARNP-BC

A 61-year-old man with HIV who had a history of renal stone development presented with bilateral renal stones within 5 months of switching from an efavirenz- to an atazanavir-based therapy. The patient’s high creatinine levels dropped after undergoing a bilateral lithotripsy along with stenting of his right ureter due to obstructive uropathy. Infrared analysis of the stone showed the composition to be 97% atazanavir.

tazanavir is a protease in- on efavirenz-based therapy. His past was admitted to a community hospi- hibitor (PI) indicated for medical history included 3 incidents tal due to complaints of worsening the treatment of human of renal stone development between right flank pain for the duration of immunodeficiency virus 1970 and 1990, which were success- 3 days. A(HIV) as part of the highly active an- fully passed without medical inter- The patient was found to have bi- tiretroviral therapy (HAART). Lim- vention. On initial evaluation, the lateral renal stones. He underwent ited data exist documenting the risk patient’s laboratory data revealed an a bilateral lithotripsy along with of patients developing urolithiasis undetectable HIV viral load, a CD4 stenting of his right ureter due to while being treated with certain anti- count in the range of 200 cells/µL, obstructive uropathy. Shortly fol- retroviral therapies. However, the risk and creatinine (Cr) and bilirubin lowing the urology procedure, the of urolithiasis due to administration levels at 0.97 mg/dL and 0.4 mg/dL, patient’s Cr dropped to 1.30 mg/ of atazanavir seems to exceed the respectively. dL. Infrared laboratory analysis of combined risk associated with other In September 2010, the option of the stone showed the composition drugs used for treatment of HIV. De- considering a PI-based HARRT regi- to be 97% atazanavir. The patient’s velopment of a right-sided urethral men was discussed with the patient atazanavir and ritonavir were dis- calculus related to atazanavir therapy due to previous data supporting that continued. Nelfinavir was started as in a patient with HIV is described in patients infected with HIV treated a new PI and emtricitabine/tenofovir this case study. with PIs may have improvements disoproxil fumarate was continued in their CD4 T-cell numbers.1 The at the standard dose. Since the med- CASE STUDY patient shared his concern about ications were changed, the patient A 61-year-old man diagnosed with his chronic low CD4 count; thus, did well without further renal issues. HIV in 1991 presented to Bay Pines the patient’s antiviral treatment was Veterans Affairs Healthcare System changed to emtricitabine/tenofovir DISCUSSION in Florida in November 2008 to es- disoproxil fumarate, atazanavir, and A limited number of cases have been tablish his medical care. He had been ritonavir. In February 2011, the pa- reported indicating patients with HIV tient’s Cr rose to 1.38 mg/dL, and who are treated with PIs may be at Dr. Baroudi is a physician in infectious disease and Dr. Flaugher is a nurse practitioner, both at Bay in July, it rose again to 1.42 mg/d. an increased risk for renal stones. In Pines Veterans Affairs Healthcare System in Florida. The tenofovir dose was adjusted the literature, an increased risk of Dr. Posnick is a dermatology resident PGY-1 at accordingly. In early August 2011, renal stones in patients treated with Palisades Medical Center in North Bergen, New Jersey. Dr. Baroudi is also an assistant professor at the patient’s Cr was elevated at atazanavir has been reported com- the University of South Florida in Tampa. 2.08 mg/dL. At that time, the patient pared with other HIV drug regi-

24 • FEDERAL PRACTITIONER • NOVEMBER 2013 mens.2 However, kidney stones have Rockwood and colleagues found especially patients with a history of also been documented in patients several patients had comorbidities, urolithiasis or renal disease, may be receiving various other PIs, such as such as hepatitis C, hepatitis B, pre- at risk for urinary crystal formation indinavir and lopinavir.2 Atazanavir existing renal disease, or a history compromising their renal function. is approved for administration as a of nephrolithiasis.5 In addition, a Considerations for alternative regi- once-daily dose of 300 mg boosted high urinary pH was a factor that mens should be explored. ● with 100 mg of ritonavir. Atazana- may have increased the likelihood vir is similar to indinavir, as both of urinary crystallization.5 The max- Author disclosures are primarily metabolized and elimi- imal solubility of atazanavir takes The authors report no actual or poten- nated by the liver through multiple place at a pH of 1.9.2 Thus, a high tial conflicts of interest with regard to pathways, including the CYP3A4 urinary pH tends to favor atazana- this article. pathway, which forms 2 inactive vir precipitation. Couzigou and col- metabolites. Both indinavir and ata- leagus reviewed stone analysis of Disclaimer zanavir are slightly soluble in water 11 patients diagnosed with ata- The opinions expressed herein are (4-5 mg/mL) with a pH-dependent zanavir-associated urolithiasis. The those of the authors and do not nec- solubility.2 Despite liver metabolism, stones contained atazanavir crystals; essarily reflect those of Federal 13% of a 400-mg dose of atazanavir 8 stones had an atazanavir core and Practitioner, Quadrant HealthCom is recoverable in the urine, of which 4 had a calcium oxalate core (1 pa- Inc., a division of Frontline Medi- 7% is unchanged; 79% is excreted in tient had 2 stones).2 cal Communications, Inc., the U.S. the feces, which represents 20% of Studies have shown that pa- Government, or any of its agencies. the drug being unchanged.3 tients taking atazanavir who devel- This article may discuss unlabeled or Common clinical adverse effects oped nephrolithiasis contained a investigational use of certain drugs. (AEs) associated with atazanavir in- stone composition in the range of Please review complete prescribing in- clude asymptomatic elevations in 40% to 100% of atazanavir concen- formation for specific drugs or drug unconjugated bilirubin; fat redis- trations.4 Rockwood compared the combinations—including indications, tribution (due to increased glucose incidence of stones in a cohort of contraindications, warnings, and ad- and lipids; however, these AEs are 6,255 patients undergoing antiretro- verse effects—before administering less frequent in atazanavir com- viral regimens containing atazanavir, pharmacologic therapy to patients. pared with other PIs); and hyper- efavirenz, lopinavir, and darunavir.5 sensitivity reactions, including rash, Of the 1,206 patients who received REFERENCES 1. Kravcik S, Magill A, Sanghvi, et al. Comparative angioedema, anaphylaxis, and bron- atazanavir, 24 (2%) developed renal CD4 T-cell responses of reverse transcriptase inhib- chospasm. Other noted AEs may stones.5 In 2006, Chang and Pella itor therapy with or without nelfinavir matched for viral exposure. HIV Clin Trials. 2001;2(2):160-170. include immune reconstitution syn- reported a patient who developed 2. Couzigou C, Daudon M, Meynard JL, et al. Uro- drome and nephrolithiasis (which atazanavir-related urolithiasis. How- lithiasis in HIV-positive patients treated with ata- zanavir. Clin Infect Dis. 2007;45(8):e105-e108. has been reported in postmarketing ever, the patient had a history of 3. Atazanavir: Drug information. UpToDate. surveillance).3 A meta-analysis from mild renal insufficiency. His Cr level Waltham, MA: UpToDate; 2013. http://www .uptodate.com/contents/atazanavir-drug 2004 to 2007 documented that of was 1.6mg/dL when the diagnosis -information?topickey=DRUG_GEN%2F9353. 1,134 patients treated with atazana- of urolithiasis was made.6 The pa- Accessed October 15, 2013. 4. Chan-Tack KM, Truffa MM, Struble KA, vir, 11 patients received a diagnosis tient underwent a cystoscopy with Birnkrant DB. Atazanavir-associated nephrolithia- of atazanavir-associated urolithiasis right ureteroscopic extraction and sis: Cases from the U.S. Food and Drug Admin- 2 istration’s adverse event reporting system. AIDS. with an overall prevalence of 0.97%. stent placement. On stone analysis, 2007;21(9):1215-1218. Chan-Tack and colleagues identified the composition was determined to 5.  Rockwood N, Mandalia S, Bower M, Gazzard B, Nelson M. Ritonavir-boosted atazanavir expo- 30 cases of nephrolithiasis in pa- be 60% atazanavir and 40% calcium sure is associated with an increased rate of renal tients infected with HIV taking an phosphate.6 stones compared with efavirenz, ritonavir-boosted lopinavir and ritonavir-boosted darunavir. AIDS. atazanavir-based regimen from De- 2011;25(13):1671-1673. cember 2002 to January 2007.4 CONCLUSION 6. Chang HR, Pella PM. Atazanavir urolithiasis. N The mechanism for PI-associated Clinicians should be aware that pa- Engl J Med. 2006;355(20):2158-2159. nephrolithiasis remains unknown. tients receiving atazanavir therapy,

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