Atazanavir-Associated Choledocholithiasis Leading to Acute Hepatitis in an HIV-infected Adult

Jacques, Amanda; Giguère, Pierre; Zhang, Guijun; Touchie, Claire; Porte, C.J.L. la

doi:10.1345/aph.1m489

Cited by 18 publications

(6 citation statements)

References 13 publications

(8 reference statements)

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“…An increase in ALP within the normal range, has been detected in both groups and this is in accordance with previous reports on atazanavir containing regimens [30]. In addition, previous studies have shown that abacavir use in combination with atazanavir-r may result in abnormal fasting lipid profile as was the case with ART_B group [31][32][33].…”

Section: Discussionsupporting

confidence: 91%

Ιn Vivo Effects of Tenofovir-DF/Emtricitabine and Abacavir/Lamivudine with Atazanavir-R on Platelet Activating Factor Metabolism in HIV Naive Patients

Papakonstantinou¹,

Chini²,

Mangafas³

et al. 2017

J Infect Dis Preve

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Antiretroviral therapy (ΑRT) has successfully decreased AIDS morbidity and mortality and increased the lifespan of HIV patients to several decades. However, numerous factors contribute with unknown mechanisms to chronic immune activation and inflammation leading to severe "non-AIDS morbidities''. Platelet Activating Factor (PAF) is a potent lipid inflammatory mediator with important role in the ''non-AIDS morbidities''. The purpose of this study was to investigate whether tenofovir-DF/emtricitabine and abacavir/lamivudine with atazanavir boosted ritonavir (ART_A and ART_B, respectively) affect in vitro PAF activity and in vivo PAF levels and metabolism.In this intent, the two ART regimens were examined in vitro against platelet aggregation induced by PAF. In addition, PAF levels and PAF metabolic enzymes were determined in HIV-1 infected volunteers before and after the initiation of antiretroviral therapy for a 12-month period.The in vitro results showed that ritonavir was the most potent inhibitor against PAF induced platelet aggregation while abacavir presented the less potent action. The in vivo results showed that tenofovir-DF/emtricitabine with atazanavir-r seems not to affect PAF levels and metabolism while abacavir/lamivudine with atazanavir-r increased bound and total PAF blood levels, PAF biosynthesis in platelets and also decreased Lp-PLA2 activity. In addition, ART_B revealed higher lyso-PAF-AT specific activity at 3rd, 6th and 9th month (p 3 =0.04, p 6 =0.04 and p 9 =0.03) compared to ART_A.In conclusion, there is a direct relation between in vitro and in vivo effect of antiretrovirals on PAF and abacavircontaining regimen activates PAF biosynthesis leading to elevated PAF levels.

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Section: Discussionsupporting

confidence: 91%

Ιn Vivo Effects of Tenofovir-DF/Emtricitabine and Abacavir/Lamivudine with Atazanavir-R on Platelet Activating Factor Metabolism in HIV Naive Patients

Papakonstantinou¹,

Chini²,

Mangafas³

et al. 2017

J Infect Dis Preve

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“…Previous reports suggested the association between ATV/r use and cholelithiasis [4]–[6]. However, the association was not demonstrated in this cohort study of 1,242 patients.…”

Section: Discussioncontrasting

confidence: 91%

“…This incidence is 10 times lower than that of ATV/r-associated renal stones reported in our previous study [3]. In fact, only 16 cases with ATV/r-induced cholelithiasis have been reported to date [4]–[6], compared with substantial number of ATV/r-associated renal stone reported by several groups [3], [12]–[16]. Thus, the potential risk of cholelithiasis in patients on PIs seems low compared to urolithiasis and may not be a major factor in the selection of ART.…”

Section: Discussionmentioning

confidence: 56%

Is Ritonavir-Boosted Atazanavir a Risk for Cholelithiasis Compared to Other Protease Inhibitors?

et al. 2013

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ObjectiveTo compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs).DesignWe conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy.MethodsThe incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure.ResultsComplicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275–6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276–7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively.ConclusionIn this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r.

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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: 69%

“…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: 92%

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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Atazanavir-Associated Choledocholithiasis Leading to Acute Hepatitis in an HIV-infected Adult

Cited by 18 publications

References 13 publications

Ιn Vivo Effects of Tenofovir-DF/Emtricitabine and Abacavir/Lamivudine with Atazanavir-R on Platelet Activating Factor Metabolism in HIV Naive Patients

Ιn Vivo Effects of Tenofovir-DF/Emtricitabine and Abacavir/Lamivudine with Atazanavir-R on Platelet Activating Factor Metabolism in HIV Naive Patients

Is Ritonavir-Boosted Atazanavir a Risk for Cholelithiasis Compared to Other Protease Inhibitors?

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

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