INTRODUCTION:

Acquired Immuno Deficiency Syndrome (AIDS) caused by HIV is a deadly syndrome for which Highly Active Anti-retroviral therapy is essential to reduce the viral load. Reduction in blood haemoglobin leading to anemia is very common especially when treated with Zidovudine ¹. This has on some occasions caused deaths². Adding to that, Zidovudinealso can cause hematotoxicity, bone marrow depression which can also cause anemia^2,3. The mechanism behind Zidovudine induced anemia is via the inhibition of heme/globin synthesis, blood cell progenitor cells. Mostly the hematotoxicity can be reversed.

Females are at most risk to anemia caused by Zidovudine⁴. After analysing the drug profile of Lamivudine we found that gastrointestinal effects such as nausea, vomiting, abdominal pain, diarrhea are the most common side effects of the drug. In this case report, we present a HIV positive patient receiving ZLN regimen with mild anemia and gastritis.

CASE REPORT:

A 38-years-old HIV positive female patient (confirmed 8 years back - 2013) was admitted in female medical ward with the chief complaints of vomiting, cough, diarrhoea, headache, and decreased appetite. On general examination, the patient was conscious and oriented, but looking very weak, hydration was poor and her vitals were BP – 170/90mm of Hg, PR – 92 beats per minute, RR – 19 cycles per minute. On system examination: CVS – S1S2 +ve, CNS – NFND (No abnormality detected). Her liver function tests (LFT) were unbalanced.

She was under regular treatment with ZLN 30 regimen (Zidovudine, Lamivudine and Nevirapine) from past 8 years. Her husband is also a known HIV patient and was expired 8 years back.

Based on general examination (pale skin, eyes are yellowish) and haematological tests (Hb – 10.2 g/dl) patient was confirmed to have anaemia. Other haematological reports shown that WBC – 7.5*10 cells/mm3, differential counts: Polymorphs 73%, Lymphocytes 15%, Monocytes 12%, platelet count – 281*10/mm³.

She has also shown the symptoms of Acute Gastroenteritis (AGE) such as vomiting, diarrhoea and indigestion. Along with the regular treatment ZLN regimen, patient was treated with parenteral anti emetic drug (ondansetron 4mg IV BD), anti-ulcer drug (Ranitidine 150mg IV BD), anti-pyretic drug (Paracetamol 500mg P/O tds), parenteral antibiotic (ciprofloxacin 500mg IV BD) and metronidazole (500mg/100ml IV TDS) for 2 days and on the last day (3^rd day) all the above following drugs are changed from IV to PO with the addition of Vitamin B complex tablet. She was advised for the medication adherence on ART drug (ZLN) and she is advised to report to physician if any symptoms of AGE occurs again & she was advised to take iron supplements because of her low haemoglobin.

ADR ANALYSIS:

The patient’s past medical and medication history was collected and analysed. It was suspected that the patient had developed mild anaemia and gastritis. The ADR profiles of the ART drugs were analysed and found that the most suspected drug for gastritis is Lamivudine and the most suspected drug to cause anaemia is Zidovudine. Causality assessment was done using Naranjo’s scales, WHO-UMC ADR assessing scale and Karch and Lasagna scale as shown in Table 1 ^{4, 5}. Severity, predictability and preventability were also assessed using Modified HartwigSeigel severity scale, Schumok and Thornton Preventability scale as shown in Table 2 ^{5, 6}.

Table 1: Causality Assessment of Suspected ADR’s

ADR

Naranjo’s Scale

WHO-UMC

Karch and Lasagna

Lamivudine induced gastritis

Possible

Zidovudine induced mild anaemia

Possible

Table 2: Severity, Predictability and Preventability of suspected ADR’s

ADR	Drug	Severity	Predictability	Preventability
Lamivudine induced gastritis	Lamivudine	Moderate level 4	Not predictable (Type B)	Definitely preventable
Zidovudine induced mild anaemia	Zidovudine	Moderate level 4	Predictable (Type A)	Definitely preventable

ADR MANAGEMENT:

General management of ADR includes drug withdrawal or suspension, reduction of drug dose or interval or/and supportive therapy ⁵. No withdrawal can be done in this case as ART must be continued for HIV infection. The patient was administered drugs for gastritis and the patient was counselled about the importance of iron intake in the diet and encouraged to take iron supplements to improve the condition as patient was not having nutritional diet due to gastritis⁶.

DISCUSSION:

In HIV positive patients who are under Highly Active Anti-Retro Viral Therapy, ADRs are likely to happen. The most common ADRs include bone marrow suppression, anemia, gastrointestinal symptoms, myalgia, loss of appetite etc.⁷. The common side effects of Lamivudine include gastrointestinal effects like diarrhea vomiting, gastritis and lactic acidosis, malaise, hepatic damage etc., The common ADRs of Zidovudine include bone marrow depression, anemia, neutropenia, anorexia, headache, vomiting etc.⁷. Since the anemia caused by the drug is mild, it can be managed by improving the diet by adding iron rich food and supplements ^8,9. We suspect that the patient has not taken a good diet because of the effects of gastritis which may have aggravated the condition. By this case report we recommend to strictly monitor the patients on this combination therapy to avoid any drastic event.

CONCLUSION:

In this case, we suspect that gastritis was caused by Lamivudine and mild anemia was caused by Zidovudine. Hence, it is necessary to monitor the patients who are on ZLN (Zidovudine+ Lamivudine+ Nevirapine) regimen for the treatment of HIV for Hemoglobin to prevent anaemia and gastric disturbances which helps in better management.

ACKNOWLEDGEMENTS:

The authors acknowledge the support and cooperation provided by the staffs of JSS Academy of Higher Education & Research, Ooty.

Conflicts of interest:

The authors declare that there is no conflict of interest.

REFERENCES:

1. Tamir Z, Alemu J, Tsegaye A. Anemia among HIV infected individuals taking art with and without zidovudine at Addis Ababa, Ethiopia. Ethiopian Journal of Health Sciences. 2018; 28(1):73.

2. Madan Mohan Rao., Rama R., Reddy GA, Samson Deepak., R Rohith., Subbiah M., Vijayan Venugopala., Case report on severe anemia and acute gastritis due to zidovudine, lamivudine, nevirapine (zln) regimen. Reactions Weekly. 2015; 1559(1):101.

3. Maheshwari P, Manju Sunny. A Prospective Study on the Knowledge, Attitude and Perception on HIV/AIDS among the Nursing and other Healthcare Professionals. Research J. Pharm. and Tech 2016; 9(9):1403-1406.

4. Belperio PS, Rhew DC. Prevalence and outcomes of anaemia inindividuals with human immunodeficiency virus: a systematic review of the literature. Am J Med 2004; 116 (Suppl 7A): 27S-43S.

5. Naranjo C.A., Busto U., Sellers E.M., Sandor P., Ruiz I., Roberts E.A., Janecek E., Domecq C., Greenblatt D.J. A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 1981; 30:239–245. doi: 10.1038/clpt.1981.154.

6. Schumock G.T., Thornton J.P. Focusing on the preventability of adverse drug reactions. Hosp. Pharm. 1992; 27:538.

7. Hartwig S.C., Siegel J., Schneider P.J. Preventability and severity assessment in reporting adverse drug reactions. Am. J. Hosp. Pharm. 1992; 49:2229–2232.

8. Sullivan PS, Hanson DL, Chu SY, Jones JL, Ward JW. Epidemiology of anaemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project. Blood 1998; 91 : 301-8.

9. Abdullahi Rabiu Abubakar, Nordin Bin Simbak, Mainul Haque. Adverse Drug Reactions: Predisposing Factors, Modern Classifications and Causality Assessment. Research J. Pharm. and Tech. 7(9): 2014;1091-1098.

Received on 29.08.2020 Modified on 17.11.2020

Research J. Pharm. and Tech 2021; 14(11):5911-5912.

DOI: 10.52711/0974-360X.2021.01027