|Year : 2021 | Volume
| Issue : 4 | Page : 249-251
A rare case of adverse drug reaction and drug interaction in a human immunodeficiency virus patient
Kaza Kavya1, MV S. Subbalaxmi1, Mutnuru Phani Chakravarty2, Soanker Radhika3, Mallika Goyal4
1 Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Radiology and Imageology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Clinical Pharmacology and Medical Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
4 Department of Ophthalmology, Apollo hospitals, Hyderabad, Telangana, India
|Date of Submission||24-Jan-2020|
|Date of Acceptance||11-Apr-2020|
|Date of Web Publication||25-Oct-2021|
M V S. Subbalaxmi
Additional Professor, Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
We are reporting a case of rifabutin-induced uveitis in a woman with human immunodeficiency virus (HIV)-tuberculosis (TB) coinfection involving the right hip. Identifying the culprit drug and tailoring the appropriate regimen was a challenge to the clinicians. We described the clinical features, ophthalmological findings, laboratory findings and radiological findings in skeletal TB and follow-up in a woman with HIV-TB coinfection. Improvement of vision on stopping rifabutin with rifampicin confirmed our diagnosis. This case highlights about adverse drug reactions and drug interactions in case of HIV and TB coinfection. Patients receiving therapy with combinations of any of these agents should be warned about signs and symptoms of uveitis and monitored closely for the development of rifabutin toxicity.
Keywords: Human immunodeficiency virus, rifabutin, tuberculosis, uveitis
|How to cite this article:|
Kavya K, S. Subbalaxmi M V, Chakravarty MP, Radhika S, Goyal M. A rare case of adverse drug reaction and drug interaction in a human immunodeficiency virus patient. J Clin Sci Res 2021;10:249-51
|How to cite this URL:|
Kavya K, S. Subbalaxmi M V, Chakravarty MP, Radhika S, Goyal M. A rare case of adverse drug reaction and drug interaction in a human immunodeficiency virus patient. J Clin Sci Res [serial online] 2021 [cited 2022 May 21];10:249-51. Available from: https://www.jcsr.co.in/text.asp?2021/10/4/249/329176
| Introduction|| |
Usual causes of uveitis include autoimmune disorders and infections. Medications in various forms of administration are recognised as increasingly important causes of uveitis. We are presenting a case of rifabutin-induced uveitis in the case of human immunodeficiency virus (HIV) infection and improvement following stopping the drug. Rifabutin is usually well tolerated and is used in the management of tuberculosis (TB) in special situations. Cases of rifabutin-induced uveitis in HIV-infected patients have been reported since 1994,,,, but it is still a rare occurrence.
| Case Report|| |
A 38-year-old homemaker was diagnosed to have HIV 1 infection 12 years ago. After 5 years, she was evaluated at a government antiretroviral therapy (ART) centre and was started on first-line ART. The patient used ART irregularly for 5 years following which she developed failure of first-line ART and CD4 cell count dropped to 24 cells/μL. She was started on second-line ART from 2017, consisting of tenofovir-, lamivudine- and ritonavir-boosted atazanavir. After 4 months, the patient presented to our institute with pain in the right hip. Magnetic resonance imaging of the right hip [Figure 1] and bone scan revealed findings suggestive of TB. She was started on anti-tuberculosis treatment (ATT), consisting of isoniazid 300 mg once a day (OD), rifabutin 150 mg OD, ethambutol 800 mg OD and pyrazinamide 1000 mg OD. After 1 month, the patient presented with a complaint of pain in the left eye and blurred vision for 4 days. In view of her HIV status, cytomegalovirus retinitis was suspected. Expert opinion of an ophthalmologist revealed visual acuity: right eye 6/6, N6; left eye 6/6, N6 and intraocular pressure: 14 mmHg in the right eye and 16 mmHg in the left eye. In the left eye, there are conjunctival trace congestion, anterior chamber and vitreous cells occasional, inferior settled vitreous exudates, and the fundus is normal. Based on the above findings, it was opined that the uveitis of the left eye was due to rifabutin. Hence, we stopped rifabutin, and the patient was started on rifampicin in the place of rifabutin. In view of drug interactions, ART was changed to dolutegravir 50 mg BD, lamivudine 150 mg BD and abacavir 300 mg BD. The patient was discharged and advised for follow-up. On follow-up, the patient's vision improved, and the same treatment strategy was continued. ATT was given for 18 months, considering multiple interactions and interruptions. Whole-body positron emission tomography-computed tomography scan done for the patient on follow-up showed no metabolically significant active disease.
|Figure 1: Magnetic resonance imaging pelvis short-T1 inversion recovery coronal view showing right femoral head (yellow circle) with hyperintensities within (oedema) and adjacent soft-tissue oedema with joint effusion. Hyperintensities also noted in the right acetabulum features suggesting tubercular aetiology|
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| Discussion|| |
Clinicians should be aware of the development of adverse drug reactions while starting any treatment, especially if the patient needs several drugs in TB and HIV infection like in our case. Drug–drug interactions are commonly encountered often in HIV patients, as we have to treat opportunistic infections and HIV simultaneously.
Immune reconstitution inflammatory syndrome (IRIS) should also be a concern in these patients, which is defined as the paradoxical worsening of pre-existing undiagnosed infectious and autoimmune conditions following the initiation of ART due to immediate improvements in immune function that occurs as levels of HIV RNA drop, and immunosuppressive effects of HIV infection are controlled and is most common in patients with CD4+ T-cell counts <50 cells/μL. In our patients, the second-line ART was started as the first-line ART failed and resulted in a low CD4 cell count of 24 cells/μl. Later, TB manifested with an improved CD4+ cell count, and we considered it as TB IRIS.
Rifampicin plays a fundamental role in the management of patients with active TB. It is possible for patients with isoniazid-resistant TB to respond well to short-course (6 months) chemotherapy, even without the benefit of INH, while those with rifampicin-resistant TB, do not. No treatment course shorter than 18 months has an acceptable success rate without a rifamycin in the regimen. Rifampicin should always be used in initial ATT unless the patient has documented rifampicin-resistant TB. Standard ATT regimens for patients infected with HIV pose a special challenge when protease inhibitors (PIs) are also indicated. PI and rifampicin usually should not be taken together, as rifampicin induces the enzymes metabolising PI.
As the patient was on PIs, rifabutin was started as rifampicin markedly lowers the serum levels of PI and non-nucleoside reverse-transcriptase inhibitors (NNRTIs) by inducing the activity of cytochrome P450 CYP3A. It may result in suboptimal antiretroviral activity and subsequently acquired drug resistance. Thus, the use of rifampicin to treat tuberculous disease in a patient receiving a PI or an NNRTI is not recommended. Rifabutin has been shown to be as effective against TB as rifampicin,, and has the advantage of being a less potent inducer of the hepatic CYP 450 enzyme system.,
Causes of uveitis in patients infected with HIV are frequently associated with opportunistic infections and rarely due to HIV itself. However, uveitis, as a side effect of rifabutin therapy, has been recognised. Possible pathogenic mechanisms may be an immune reaction or direct drug toxicity. Direct rifabutin toxicity was advocated by dose dependency, cumulative time dependency and involvement of both eyes in most cases and reversibility on drug discontinuation. Ophthalmologists and physicians treating HIV, and TB should be aware of this adverse drug reaction. If uveitis develops, rifabutin therapy should be discontinued promptly.
We are reporting this case to bring awareness about drug interactions and a rare adverse drug reaction of rifabutin. The risk of rifabutin-associated uveitis may be increased in patients receiving concurrent therapy with clarithromycin or fluconazole because of drug interactions. Patients receiving therapy with combinations of any of these agents should be warned about signs and symptoms of uveitis and be monitored closely for the development of rifabutin toxicity. This case also highlights the adverse drug reaction and drug–drug interaction in the case of HIV and TB coinfection.
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Conflicts of interest
There are no conflicts of interest.
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