What is the management approach for a patient with chronic kidney disease (CKD), human immunodeficiency virus (HIV), and ileocecal tuberculosis, currently on antitubercular therapy (ATT) and antiretroviral therapy (ART) with dolutegravir (Tivicay), abacavir (Ziagen), and tenofovir (Viread), presenting with hyperbilirubinemia and pancytopenia?

From the Guidelines

The patient should immediately discontinue tenofovir due to its potential nephrotoxicity, as suggested by the elevated bilirubin levels and pancytopenia, and consider replacing it with lamivudine while maintaining dolutegravir and abacavir if tolerated, as recommended by 1. The management of this complex patient requires a multifaceted approach, considering the potential drug toxicities associated with both antitubercular therapy (ATT) and antiretroviral therapy (ART). The presence of hyperbilirubinemia and pancytopenia in a patient with chronic kidney disease (CKD), human immunodeficiency virus (HIV), and ileocecal tuberculosis, who is on ATT and ART with dolutegravir, abacavir, and tenofovir, strongly suggests drug toxicity.

• The patient's medication regimen should be temporarily discontinued to allow for urgent laboratory testing, including liver function tests, complete blood count with differential, CD4 count, HIV viral load, and drug levels if available.
• A modified ATT regimen avoiding hepatotoxic drugs, such as a rifampin-sparing regimen with levofloxacin, ethambutol, and amikacin, should be considered once the patient is stabilized, as suggested by 1.
• The ART regimen should be adjusted by removing tenofovir, which has been associated with nephrotoxicity, particularly in patients with CKD, as noted in 1.
• Renal function must be closely monitored with regular estimation of glomerular filtration rate and proteinuria assessment, and supportive care including hydration, possible transfusion for severe anemia, and nutritional support is essential.
• The patient requires weekly monitoring of liver function, blood counts, and renal parameters during the initial adjustment period, with multidisciplinary involvement from infectious disease, nephrology, and hepatology specialists, as the patient's compromised renal function affects drug clearance, as discussed in 1 and 1. Key considerations in managing this patient include:
• The potential for drug-drug interactions, particularly with the use of rifampin and other hepatotoxic agents in the ATT regimen, which may exacerbate liver dysfunction.
• The need for careful monitoring of renal function, given the patient's CKD and the potential nephrotoxic effects of certain antiretroviral and antitubercular agents.
• The importance of maintaining effective ART to control HIV replication and prevent disease progression, while minimizing the risk of drug toxicity and adverse effects. By prioritizing the patient's renal function, minimizing drug toxicity, and maintaining effective ART, it is possible to optimize the management of this complex patient and improve their overall morbidity, mortality, and quality of life, as emphasized by 1 and 1.

From the Research

Management Approach

The patient's presentation with hyperbilirubinemia (s.bilirubin of 5.4) and pancytopenia requiring blood transfusion, while on antitubercular therapy (ATT) and antiretroviral therapy (ART) with dolutegravir, abacavir, and tenofovir, necessitates a careful management approach.

• The patient's chronic kidney disease (CKD) and human immunodeficiency virus (HIV) status, along with ileocecal tuberculosis, complicate the clinical picture.
• The presence of pancytopenia and hyperbilirubinemia may indicate a hemophagocytic syndrome, as described in a case report 2, which can be associated with tuberculosis, especially in immunocompromised patients.
• The API TB Consensus Guidelines 2006 3 provide guidance on the management of tuberculosis in special situations, including HIV co-infection, but do not specifically address the management of hyperbilirubinemia and pancytopenia in this context.
• The use of dolutegravir, abacavir, and tenofovir as ART is supported by studies such as the one by 4 and 5, which demonstrate the efficacy and safety of these regimens in treatment-naive patients, including women with HIV-1 infection.
• However, the management of tuberculosis in patients with chronic liver disease, as discussed in 6, highlights the need for careful consideration of hepatotoxicity and liver function monitoring when using anti-tuberculosis drugs.

Considerations for Management

• Close monitoring of liver function tests and bilirubin levels is essential to assess the severity of hyperbilirubinemia and potential hepatotoxicity.
• The patient's CKD status requires careful consideration of drug dosing and potential nephrotoxicity, as discussed in 3.
• The use of blood transfusions may be necessary to manage pancytopenia, but the underlying cause of the condition should be investigated and addressed.
• A bone marrow biopsy or aspiration, as suggested in 2, may be considered to investigate the cause of pancytopenia and rule out other conditions such as hemophagocytic syndrome.
• The patient's ART regimen should be continued, with close monitoring of viral load and CD4 cell count, as well as potential drug interactions with ATT.
• The ATT regimen should be adjusted according to the patient's response and potential side effects, with consideration of hepatotoxicity and nephrotoxicity.