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CASE REPORT
Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 57-59

Tenofovir-induced quadriparesis


1 Department of Pharmacology, Rajiv Gandhi Institute of Medical Sciences, Kadapa, Andhra Pradesh, India
2 Department of General Medicine, Rajiv Gandhi Institute of Medical Sciences, Kadapa, Andhra Pradesh, India

Date of Submission31-Aug-2018
Date of Acceptance19-Oct-2018
Date of Web Publication14-May-2020

Correspondence Address:
Dr. Ashalatha Muppur
Department of Pharmacology, Rajiv Gandhi Institute of Medical Sciences (RIMS), Kadapa - 516 003,Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_82_18

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  Abstract 


With an ever-increasing trend in the side effects of antiretroviral therapy (ART), usage of new regimens to decrease the mortality and morbidity has come into picture. Here we report a case of tenofovir-induced hypokalemic paralysis. A 60-year-old female patient came to a medical outpatient department with quadriparesis. History revealed that she was diagnosed with HIV 6 years back and was on zidovudine, lamivudine, and efavirenz. Three months later, she developed severe anemia because of which zidovudine was replaced by tenofovir. On evaluation, there was hypokalemia with appropriate electrocardiography changes. As previous literature showed association of hypokalemia with tenofovir, we attributed this finding to the usage of tenofovir. ART was stopped, and the patient was given potassium supplements and potassium-rich diet. There was dramatic improvement with the treatment and the patient regained muscle strength. After 1 week, she was put on other alternative regimen consisting of abacavir, lamivudine, and efavirenz. Her CD4 count was improved without any complaints. The patient was monitored on outpatient basis in ART center.

Keywords: Abacavir, antiretroviral therapy, hypokalemic paralysis, tenofovir


How to cite this article:
Muppur A, Sidhartha J M, Allahuddin S. Tenofovir-induced quadriparesis. J NTR Univ Health Sci 2020;9:57-9

How to cite this URL:
Muppur A, Sidhartha J M, Allahuddin S. Tenofovir-induced quadriparesis. J NTR Univ Health Sci [serial online] 2020 [cited 2020 May 30];9:57-9. Available from: http://www.jdrntruhs.org/text.asp?2020/9/1/57/284324




  Introduction Top


According to 2018 statistics, the estimated population with HIV infection is 2.1 million in India.[1] Today, about 528 antiretroviral therapy (ART) centers are established in India under National AIDS Control Organization (NACO), of which 41 are present in Andhra Pradesh. ART should be initiated at any World Health Organization (WHO) clinical stage with CD4 count <250 or WHO stage 3 or 4 irrespective of CD4 count. In both these cases, cotrimoxazole is started prophylactically. Classes of drugs available for ART in India are nucleoside reverse transcriptase inhibitors (NRTI) which include zidovudine (AZT), stavudine (d4T), lamivudine (3TC), didanosine (dd1), abacavir (ABC), and tenofovir (TDF). The second group includes non-nucleoside reverse transcriptase (NNRTI) which include nevirapine (NVP) and efavirenz (EFV). The third group includes protease inhibitors which include saquinavir (SQV), ritonavir (/r), nelfinavir (NFV), amprenavir, indinavir (IDV), and atazanavir (ATV). Combination therapy usually consists of three drugs from at least two different classes which is referred as highly active antiretroviral therapy (HAART).[2] Most HAART regimens consist of three drugs, of which two are NRTIs (backbone) and one PI/NNRTI (base).


  Case Report Top


A 60-year-old female patient presented to ART center, Kadapa, Andhra Pradesh, with generalized weakness of both the upper and lower limbs. She had no other complaints. History revealed that she was diagnosed with HIV infection 6 years back (2012) when she went to a physician for mild fever. Her CD4 count was 240 cells/mm[3]. Although her fever subsided in few days, because her CD4 count was less, she was started withfirst-line regimen (according to NACO), that is, zidovudine[3] (300 mg) + lamivudine (150 mg) + efavirenz (600 mg) twice daily from March 2012 to October 2016. In November 2016, she developed severe anemia with Hb <6 g/dL, and one packed cell blood transfusion was done (according to old medical reports). Later, she was put on tenofovir (300 mg) + lamivudine (150 mg) + efavirenz (600 mg) once daily. This was the regimen now she was on.

On examination, the patient was conscious and coherent. She was hemodynamically stable with pulse rate 84, blood pressure 140/80 mmHg, and SpO292% at room temperature. Her abdomen was soft, with no abnormality detected. Her respiratory system and cardiovascular system were normal.

Physical examination of CNS: On inspection, no voluntary movements were observed in both the upper and lower limbs. On palpation, hypotonia was observed in all the four limbs. The motor power grade was 3/5 {proximal and distal} in all the four extremities. Deep tendon reflexes were absent. Plantars were equivocal, suggestive of predominant lower motor neuron (LMN) type of quadriparesis, and higher centers were normal.

The patient's weight was normal, with no HIV-related skin problems and no enlarged lymph nodes (post cervical nodes). Her oral cavity (tongue and roof of mouth) was normal. No hepatosplenomegaly or jaundice was noted, and anogenital lesions were absent.

Routine investigations including hematology, renal function test, blood sugar, liver function test, CD4 count, serum electrolytes (sodium, potassium, and chlorine), and urine microscopy were done. X-ray (PA view), HbsAg, ultrasound abdomen, sputum for AFB, and VDRL test were done.

According to hemogram, Hb was normal, and CD4 count was found to be 250 cells/mm[3]. Electrolyte abnormality mainly seen was serum potassium which was 2.7 mEq/L. Electrocardiography (ECG) [Figure 1][4] changes observed included ST segment sagging, with T-wave depression and U-wave elevation, suggesting hypokalemia. Here ECHO was normal. All the other tests were also normal. With this background, we diagnosed our case as “tenofovir-induced quadriparesis” due to hypokalemia.
Figure 1: ECG of hypokalemia

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The patient was admitted and was monitored closely. Potassium supplements via oral and IV routes and potassium-rich diet were given. The potassium levels increased to 4.7 mEq/L on the fifth day. There was subsequent dramatic improvement of muscle power in all the four extremities.

Tenofovir therapy was stopped and replaced with abacavir (600 mg) along with lamivudine and efavirenz. CD4 count was monitored, which raised to 350 cells/mm[3], and there were no other complaints. The patient was discharged and monitored on outpatient basis in ART center.


  Discussion Top


ECG showed hypokalemia in this patient. Hypokalemia[5] is a condition where the levels of potassium in the serum falls below 3.5 mmol/L. Severe hypokalemia may cause muscle weakness, myalgia, and hyporeflexia.

The scientific term quadriparesis[6] means muscle weakness affecting all the four limbs. Typical causes are trauma, stroke, diseases such as transverse myelitis, electrolyte imbalance, and congenital disorders. Higher centers were normal. The quadriparesis appeared mostly like LMN type with hypotonia. After excluding other causes, hypokalemia was decided as the culprit.

The first regimen started in this patient was a combination of AZT, 3TC, and EFV. AZV is an NRTI. The mechanism of action is inhibition of enzyme reverse transcriptase that HIV uses to make DNA, and the side effects that occur after long-term therapy are anemia, neutropenia, cardiomyopathy, and hepatitis. Early side effects include nausea, vomiting, heart burn, and headache. 3TC is an NRTI and the action is similar to AZT. Side effects are nausea, fatigue, headache, cough, and nasal congestion. EFV is an NNRTI. Its action is similar to AZT. The common adverse effects are neuropsychiatric effects. Tenofovir disoproxil[7] is an NRTI. The common side effects are nausea, diarrhea, depression, rash, and sleep disturbances. Tenofovir is also used for treatment of hepatitis B infection.

Although the exact mechanism for tenofovir-induced hypokalemia is not known, it may be due to type 2 renal tubular acidosis.[8] In this condition, there is failure of proximal tubular cells to reabsorb bicarbonate ions resulting in increased excretion of potassium ions. The other less popular theory advocated is type 1 renal tubular acidosis where there is failure of intercalated cells to secrete hydrogen ions and reclaim potassium ions in the distal tubule of kidney. Whatever may be the theory, the pathophysiology is hypokalemia resulting in quadriparesis. The rare complications of tenofovir are Fanconi syndrome[9] (due to damage to tubules of kidney) resulting in proteinuria, glucosuria, lactic acidosis, and hypokalemia.

The new drug used in the place of tenofovir is abacavir.[10] ABC is an NRTI. The action is similar to AZT. The common adverse effects include nausea, loss of appetite, and insomnia. Rare side effects are hypersensitivity reactions, lactic acidosis, and lipodystrophy. In this case, the patient tolerated ABC well, and her CD4 counts improved from 250 to 350 cells/mm[3].


  Conclusion Top


Tenofovir is a relatively safe drug and now has becomefirst-line regimen in India under NACO-prescribed ART. The associated consequences of tenofovir-related hypokalemia may be life-threathening. Physicians should be aware of this complication while prescribing tenofovir. It is better while initiating tenofovir, to make a practice to closely follow the patient's serum electrolytes and urine analysis every 3 months for the first 12–18 months.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sharma, D.HIV/AIDS: A life threatening disease. The Pharma Innovation. TPI Int J 2013;2:146-61.  Back to cited text no. 1
    
2.
Moore RD, Chaisson RE. Natural history of HIV infection in the era of combination antiretroviral therapy.AIDS J1999;13:1933-42.  Back to cited text no. 2
    
3.
Quan Y, Rong L, Liang C, Wainberg MA. Reverse transcriptase inhibitors can selectively block the synthesis of differently sized viral DNA transcripts in cells acutely infected with human immunodeficiency virus type 1.J Virol 1999;73:6700-7.  Back to cited text no. 3
    
4.
Levis JT. ECG diagnosis: Hypokalemia. Perm J 2012;16:57.  Back to cited text no. 4
    
5.
Tsimihodimos V, Kakaidi V, Elisaf M. Cola-induced hypokalaemia: Pathophysiological mechanisms and clinical implications. Int J Clin Pract 2009;63:900-2.  Back to cited text no. 5
    
6.
Young R. Chapter 15: Spastic paresis. In Burks J, editor. Multiple Sclerosis – Diagnosis, Medical Management and Rehabilitation. New York: Demos Medical Publishing, Inc.; 2000. p. 299.  Back to cited text no. 6
    
7.
Ustianowski A, Arends JE. Tenofovir: What we have learnt after 7.5 million person-years of use. Infect Dis Ther 2015;4:145-57.  Back to cited text no. 7
    
8.
Kearney BP, Yale K, Shah J, Zhong L, Flaherty JF. Pharmacokinetics and dosing recommendations of tenofovir disoproxil fumarate in hepatic or renal impairment. Clin Pharmacokinet 2006;45:1115-24.  Back to cited text no. 8
    
9.
Irizarry-Alvarado JM, Dwyer JP, Brumble LM, Alvarez S, Mendez JC. Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: A report of 3 cases. AIDS Read2009;19:114-21.  Back to cited text no. 9
    
10.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J,et al. HLA-B*5701 screening for hypersensitivity to abacavir.N Engl J Med 2008;358:568-79.  Back to cited text no. 10
    


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