Urolithiasis in HIV-Positive Patients Treated with Atazanavir

Couzigou, C.; Daudon, Michel; Meynard, Jean Luc; Lebas, Françoise Borsa; Higueret, D.; Escaut, L.; Zucman, David; Liotier, Jean-Yves; Quencez, Jean-Louis; Asselah, Karine; May, Thierry; Néau, Didier; Vittecoq, D.

doi:10.1086/521930

Cited by 81 publications

(56 citation statements)

References 8 publications

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“…Unfortunately, ATV could not be identified in the crystals, because those obtained were too small in size to analyze the components. Nevertheless, all these findings are fully consistent with those found in the patients with ATV crystal nephropathy (17,18).…”

Section: Discussionsupporting

confidence: 90%

“…He did not show a high concentration of uric acid in the serum and the urine, which eliminated the possibility of uric acid crystals. Importantly, it is generally accepted that ATV crystal nephropathy alone does not induce progressive renal impairment (18). It is possible that the preexisting chronic renal injuries due to the previous administration of TDF may have rendered the patient more susceptible to the renal toxicity of ATV.…”

Section: Discussionmentioning

confidence: 99%

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Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

et al. 2012

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This report presents a human immunodeficiency virus (HIV) patient that developed a slowly progressive renal impairment over years under highly active antiretroviral therapy (HAART). The renal biopsy showed diffuse tubulointerstitial nephritis accompanied by crystal formations that were surrounded by multinuclear giant cells. Furthermore, rod-like crystals were detected in the urinary sediments. Tenofovir and Atazanavir were thought to be the causative drugs for the renal injury. Therefore, the possibility of HARRT-induced nephrotoxicity should be considered in HIV-infected patients, even though the activity of HIV is controlled by such therapies.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

et al. 2012

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“…It is well known that ATV/r is associated with renal lithiasis and there have been reports of ATV-associated choledocholithiasis [2][3][4]. We can postulate that our patients may have had semicircular canal lithiasis causing similar symptoms, though the short duration between onset and starting the drug and the complete resolution of symptoms after stopping the drug make this mechanism less likely.…”

Section: Discussionmentioning

confidence: 68%

“…In this case the patient had a 3-year history of ATV, 3TC and TDF use and was admitted to hospital for objective vertigo, nausea and sweating triggered by postural changes. He was diagnosed as having lithiasis of his posterior semicircular canal, possibly related to his ATV use [1].It is well known that ATV/r is associated with renal lithiasis and there have been reports of ATV-associated choledocholithiasis [2][3][4]. We can postulate that our patients may have had semicircular canal lithiasis causing similar symptoms, though the short duration between onset and starting the drug and the complete resolution of symptoms after stopping the drug make this mechanism less likely.…”

mentioning

confidence: 93%

Atazanavir Causing CNS Toxicity? Unexplained Neurological Symptoms in Two Patients Recently Started on Atazanavir

Toby¹

2013

J AIDS Clinic Res

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CaseA 39-year-old, homosexual man from the Philippines was diagnosed with HIV (no resistance mutations, CD4 count 315 cells/ µl, HIV viral load 120,033 copies/ml) and hepatitis B (HBV) infections (HBV e antigen negative , HBV DNA 2349 IU/ml. Three months after diagnosis he was started on a one-pill combination regimen of tenofovir, emtricitabine and efavirenz (TDF/FTC/EFV). After 10 days he developed a widespread erythematous rash without mucosal involvement and TDF/FTC/EFV was stopped immediately. Routine biochemistry and hematology blood tests done at this time were all within normal limits and he was started on a new regimen of TDF/FTC and ritonavir-boosted atazanavir (ATV/r; 300 mg/100 mg) once daily.He returned to the clinic 2 weeks later complaining of weakness, mild headache, agitation and difficulty sleeping in the first week of taking his new regimen. This had progressed and after the second week, 4 hours after taking his antiretrovirals in the morning he became disorientated in time and place, described severe vertigo and became tremulous. These episodes occurred for 5 consecutive days and lasted approximately 3 hours each time.He tried taking his antiretrovirals at night; his partner reported that 3 hours after taking the medication he woke up from sleep completely disorientated and complained of nausea and extreme vertigo rendering him unable to walk. The patient stopped his antiretrovirals of his own volition after this night-time episode. He was seen in clinic 48 hours later by which time he was completely asymptomatic; he was apyrexial with a normal physical examination. Hematological and biochemistry blood tests were unremarkable apart from an elevated alanine aminotransferase (ALT) of 127 IU/L (4-59 IU/L).The patient's symptoms were attributed to ATV and not FTC having not experienced these symptoms taking FTC previously. His regimen was changed to FTC/TDF and ritonavir-boosted darunavir (DRV/r; 800 mg/100 mg) and he was seen 2 weeks later in clinic. He reported no further symptoms and his ALT had returned to normal.A second patient was an Ecuadorian woman diagnosed HIV positive with a CD4 count of 10 cells/µl at diagnosis. She was thus started on TDF, lamivudine (3TC) and lopinavir/ritonavir (LPV/r; 400 mg/100 mg). She had remained stable on this regimen for 2 years with virological suppression to less than 50 copies/ml. She requested simplification of the regimen due to high pill burden and twice daily dosing and her LPV/r was thus switched to ATV/r 300 mg/100 mg along with her existing TDF and 3TC.The patient returned to clinic after 10 days complaining of mild dizziness in the first week, which progressed to severe positional vertigo, tremulousness and nausea in the second week. The examination was unremarkable but turning her head provoked extreme vertigo. She was apyrexial and all other vital signs were within normal limits. Routine biochemistry and hematology blood tests done at this time were within normal parameters as were her inflammatory markers. As the only recent change had been th...

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“…In one retrospective study the prevalence of ATV-associated urolithiasis was 0.97%. 49 Patients with low water intake, high urinary pH, and prior history of urinary stones are at higher risk for ATV-associated urine crystallization.…”

Section: Toxicitymentioning

confidence: 99%

Role of atazanavir in the treatment of HIV infection

Soriano¹

2008

TCRM

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Atazanavir (ATV) is one of the latest protease inhibitors (PI) approved for the treatment of HIV infection. The drug has a relatively long-life (∼7 h) and large inhibitory quotient which allows once daily administration. It is generally well tolerated and the main side effect is hyperbilirubinemia, since ATV inhibits the hepatic uridin-glucoronyl-transferase. A signature mutation at the protease gene, I50L, may confer loss of susceptibility to the drug. Interestingly, it produces hypersusceptibility to all other PIs. When ATV is pharmacokinetically boosted with ritonavir (r) 100 mg/day, a greater genetic barrier for resistance is achieved, and generally more than 3 major PI resistance associated mutations are needed to result in ATV resistance. In drugnaïve subjects, regimens based on ATV/r have shown non-inferiority compared to lopinavir (LPV)/r (CASTLE study) or fosamprenavir/r (ALERT trial), generally with improved tolerance (less diarrhea and dyslipidemia). Given its good tolerance and convenience, ATV has been proven to be successful as a simplifi cation strategy in switch studies (ie, SWAN and SLOAT) conducted in patients with complete virological suppression under other PI-based regimens. Finally, ATV/r-based combinations have shown to be equivalent in terms of viral response to other PI/r-containing regimens, including LPV/r, in rescue interventions in patients failing other PI regimens (ie, studies AI424-045 and NADIS).

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Urolithiasis in HIV-Positive Patients Treated with Atazanavir

Cited by 81 publications

References 8 publications

Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

Atazanavir Causing CNS Toxicity? Unexplained Neurological Symptoms in Two Patients Recently Started on Atazanavir

Role of atazanavir in the treatment of HIV infection

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