viral enteritis is a common gastrointestinal ( gi ) disorder in human immunodeficiency virus ( hiv)-infected patients . several viruses such as cytomegalovirus ( cmv ) , herpes simplex virus ( hsv ) , adenovirus ( adv ) , norovirus , astrovirus , and rotavirus , have been implicated in the causation of viral enteritis . although it can affect the entire gi tract , it frequently involves the esophagus and colon . here , we present a case of a female patient , on tenofovir - based antiretroviral therapy , who was started on ganciclovir for suspected cmv infection . she presented with vomiting , anorexia , altered sensorium , and later there was gradual deterioration in her renal function , implicating a drug interaction between tenofovir and ganciclovir . to the best of our knowledge , this is the first case report in which the interaction between ganciclovir and tenofovir is reported . a woman of age 51 years was diagnosed with hiv 1 infection , five years ago , and since then was under antiretroviral therapy ( art ) with tenofovir 300 mg , emtricitabine 200 mg , and efavirenz 600 mg , once daily . ganciclovir 250 mg orally and fluconazole 150 mg orally once daily were started 14 days prior , at an outside hospital , for loss of appetite and dysphagia . she presented to the emergency department of our hospital with complaints of vomiting and decreased food intake of 10 days duration , with altered sensorium of one - day duration . there was no history of fever , dyspnea , chest pain or palpitations , diarrhea or decreased urine output . the patient underwent left nephrectomy in 2003 , for unknown reasons and for which records are not available . on examination , she was found to have pallor , with no signs of icterus , cyanosis , lymphadenopathy , clubbing and pedal edema . blood glucose levels were low , so she was started on 25% dextrose and her sensorium improved . she was started on oxygen inhalation , intravenous fluids , infusion of sodium bicarbonate ( nahco3 ) , infusion of potassium chloride ( kcl ) and ryle 's tube feeding . routine investigations were done , which revealed , on day 1 , a serum creatinine of 1.5 mg / dl , blood urea of 49 mg / dl , and arterial blood gas ( abg ) showed metabolic acidosis . on the second day , her serum creatinine was 1.9 mg / dl , blood urea was 68 mg / dl , serum electrolytes were na 165 meq / l , k 2.4 meq / l , and cl 123 meq / l . an ultrasound abdomen done on the third day revealed post left nephrectomy and grade ii renal parenchymal changes in the right kidney . magnetic resonance imaging ( mri ) showed diffuse cerebral atrophy and her cd4 count was 99 cells / microliter . tablet co - trimoxazole ( 160 mg/800 mg ) , one tablet , once daily , was added for prevention of opportunistic infection . serum creatinine and blood urea gradually increased to 2 mg / dl and 69 mg / dl respectively on the fourth day . on the fourth day , the case was referred to a clinical pharmacologist , for dosage adjustment of the drugs the patient was taking , as acute kidney injury was diagnosed , with a rise in the renal function parameters . after reviewing the case details , a drug interaction was suspected between tenofovir and ganciclovir , which might have caused a rise in the tenofovir concentrations and led to acute kidney injury . therefore , taking into account this drug interaction , on the fourth day , art and ganciclovir were withheld . on the fifth day , serum creatinine decreased from 2 mg / dl to 1.7 mg / dl and blood urea decreased from 69 mg / dl to 51 mg / dl . on the fifth day , the patient was discharged at request . gastroenteritis is one of the most common and debilitating conditions that affect individuals with acquired immunodeficiency syndrome ( aids)/hiv . several viruses have been implicated in the causation of gastroenteritis , of which , cmv is the most common opportunistic agent in hiv - infected patients . although it can infect the entire gastrointestinal tract ( git ) , it frequently involves the esophagus and colon . in a study done on hiv - positive patients on art , 22 out of the 26 virus - positive patients were infected with cmv which included 11 single infections , two coinfections with adenovirus or herpes simplex virus-2 and five coinfections with parasites . despite the widespread use of highly active antiretroviral therapy ( haart ) in hiv infection , hiv - infected patients often present with non - specific gi symptoms . in this case , the patient was started on oral ganciclovir empirically for suspected cmv infection , by a private practitioner . however , when routine investigations were done for evaluating the patient 's condition , it was observed that there was a persistent rise in the serum creatinine and blood urea levels during the first three days of admission . on the third day , grade ii renal parenchymal changes were noticed on an ultrasound of the abdomen , which prompted a call to the clinical pharmacologist for dosage adjustment of the antiretroviral drugs and ganciclovir , in this patient . after taking the detailed history , there were three important suggestions made , one was a suspected drug interaction between tenofovir and ganciclovir , which could have increased the tenofovir concentrations , leading to acute kidney injury , second , to hold back administration of tenofovir and ganciclovir , and third , substitution of oral ganciclovir by valganciclovir , if treatment for cmv infection was unavoidable . in addition , dosage adjustments were recommended for fluconazole , emtricitabine , and trimethoprim - sulfamethoxazole , as the creatinine clearance was approximately 33 ml / minute . it was recommended that fluconazole be administered in a dose of 50 mg once daily , emtricitabine 200 mg every 48 hours , and trimethoprim - sulfamethoxazole at half the usual dose . in this case , the patient was under treatment with tenofovir since five years , with good tolerability , but there was a persistent rise of serum creatinine during the first three days of admission , from 1.5 to 2 mg / dl , which was most probably due to tenofovir - induced nephrotoxicity . a sudden onset of intolerability with tenofovir , raised suspicion into what factors could have triggered this event . risk factors for tenofovir - induced glomerular filtration rate ( gfr ) reduction include advanced age , low body weight , higher serum creatinine levels before starting tenofovir treatment , comorbidities ( diabetes , hypertension , hepatitis c virus ( hcv ) coinfection ) , concomitant nephrotoxic medications , advanced hiv infection ( low cd4 counts , aids ) , and male sex according to a multivariate analysis done on postmarketing data . in this case , the factors that need attention include solitary kidney and concomitant medications . the evidence from living donors indicates that renal function , as measured by gfr , shows an initial decline of 25 - 35% following donation , with a long - term gfr around 10 ml / minute per 1.73 m , less than that expected without nephrectomy . there is no evidence of an accelerated decline when compared with the age - matched controls . however , we do not know , the indication for which nephrectomy was done in this case . a review article by mark a. perazella , on renal vulnerability to drug toxicity , that reviewed the factors that increase vulnerability of the kidney to potential toxins , identifies patient - specific factors , kidney - specific factors , and drug - specific factors , among which , a solitary kidney is not listed . therefore , in the light of the available literature it seems that the solitary kidney might not have contributed to acute kidney injury in this case . among the concomitant medications prescribed , emtricitabine , trimethoprim - sulfamethoxazole , and fluconazole are excreted by the kidney and therefore dosage adjustments were recommended , but they are not known to cause nephrotoxicity . although ganciclovir is not nephrotoxic , it 's interaction with tenofovir was suspected , as the timing at which the events occurred , coincided with the time at which ganciclovir was started . tenofovir is primarily excreted by the kidneys , by glomerular filtration and active tubular secretion . twenty to thirty percent of tenofovir is excreted unchanged in the urine through active secretion by the proximal tubular cells . organic anion transporter 1 ( oat1 ) is the main transporter taking tenofovir into the proximal tubular cell . once inside this mitochondrial rich cell type , tenofovir must be extruded into the tubular lumen by mrp-2 and mrp-4 . therefore , blocking tenofovir extrusion by mrp-2 and mrp-4 by pharmacological interference boosts tenofovir nephrotoxicity . ganciclovir being a mrp-4 inhibitor , may have raised the concentrations of tenofovir , leading to nephrotoxicity . treatment of cmv enterocolitis requires parenteral therapy , with either ganciclovir ( 5 mg / kg twice daily ) or foscarnet ( 90 mg / kg twice daily ) . in an open - label , randomized study , comparing a two - week course of foscarnet with ganciclovir , no significant difference in clinical response was found between the two therapies . around 75% of the patients had good clinical and endoscopic responses , with the disappearance of the inclusion bodies , as determined histologically . the use of oral ganciclovir in the maintenance of gi remission has not been evaluated . most of the experience has been established in transplant recipients and in patients with aids , who have cmv retinitis , for which ( oral ) valganciclovir is of equal efficacy to intravenous ganciclovir , for treating cmv disease . on account of the poor bioavailability of oral ganciclovir , as the therapeutic effect is uncertain , valganciclovir , a valine ester prodrug of ganciclovir , was suggested . however , as valganciclovir also inhibits mrp-4 , its co - administration with tenofovir could raise the concentrations of tenofovir , leading to nephrotoxicity . subsequent to the clinician 's decision of stopping ganciclovir and art , the serum creatinine and blood urea showed a decline on the fifth day . as ganciclovir or valganciclovir are the drugs of choice for cytomegalovirus infections that are commonly encountered opportunistic infections in hiv - infected individuals , in whom tenofovir - based art is better tolerated ( the most commonly employed art regimen ) , this interaction assumes clinical relevance . to the best of our knowledge , there is no case report published in this regard , and this would be the first one . therefore , whenever a patient is on tenofovir - based art , ganciclovir or valganciclovir co - administration should be avoided . in case ganciclovir or valganciclovir are indicated for treatment of the co - infection , then tenofovir may be substituted with any other appropriate antiretroviral drug , to preserve renal function .
viral enteritis is an important gastrointestinal disorder in human immunodeficiency virus ( hiv)-infected patients . 
 cytomegalovirus ( cmv ) is the most common opportunistic agent in these patients . 
 as ganciclovir and tenofovir are the most commonly used drugs for the treatment of cmv and hiv infection , respectively , this case report showcases the potentiality of drug interaction as well as the safety measures to be taken when using these two drugs together in unavoidable situations .