HIV PEP in Patients with Altered Liver and Renal Function
In patients with impaired liver and renal function requiring HIV post-exposure prophylaxis, use tenofovir alafenamide (TAF)-based regimens rather than tenofovir disoproxil fumarate (TDF), specifically bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days, with dose adjustments and enhanced monitoring based on the severity of organ dysfunction. 1, 2
Preferred Regimen Selection Based on Organ Function
For Renal Impairment
TAF-based regimens are strongly preferred over TDF-based regimens because TAF has significantly less impact on renal function and lower rates of proximal renal tubulopathy compared to TDF, even though these adverse events are less common with short-duration PEP. 1, 2
First-line choice: BIC/FTC/TAF (one tablet once daily for 28 days) provides optimal renal safety while maintaining efficacy. 2, 3
Alternative option: Dolutegravir 50mg once daily plus emtricitabine/tenofovir alafenamide 200mg/25mg once daily for 28 days if BIC/FTC/TAF is unavailable. 2
Dose adjustments for emtricitabine and tenofovir may be required depending on creatinine clearance; baseline renal function (creatinine, eGFR) must be assessed before initiating any tenofovir-based regimen. 2, 4
Enhanced creatinine monitoring is required during the 28-day PEP course for patients with baseline renal impairment. 1
For Hepatic Impairment
Liver disease with cirrhosis may contraindicate certain antiretroviral regimens or require dosage modifications in persons with Child-Pugh class B or C disease. 1
For patients with hepatitis B virus (HBV) co-infection, regimens containing agents active against HBV are preferred (tenofovir and lamivudine/emtricitabine-containing regimens). 1
Additional monitoring for liver transaminase elevation is required during and after PEP, as elevation can occur when taking or discontinuing antiretrovirals and is more common in persons with HBV or hepatitis C virus (HCV) infection. 1
Drug-induced liver injury is more common in patients with HCV/HIV co-infection, necessitating closer monitoring. 1
For patients with HBV/HCV co-infection or those on direct-acting antiviral (DAA) agents, expert consultation with clinicians knowledgeable in antiretroviral medications is strongly recommended due to risk of HBV reactivation. 1
Critical Monitoring Protocol
Baseline Assessment (Before Starting PEP)
Complete blood count, renal function tests (creatinine, eGFR), and hepatic chemical function tests must be performed at baseline. 1
Assess hepatitis B vaccination status and anti-HBs antibody levels immediately if HBV exposure is possible. 2
During PEP Course
Repeat toxicity monitoring at 2 weeks after starting PEP at minimum, with scope of testing determined by pre-existing medical conditions and specific drugs in the regimen. 1
For patients with baseline organ dysfunction, more frequent monitoring (weekly or biweekly) may be warranted based on severity. 1
Monitor for crystalluria, hematuria, hemolytic anemia, and hepatitis if protease inhibitors are used (though these are not preferred in modern regimens). 1
Regimens to Avoid in Organ Dysfunction
Contraindicated or High-Risk Options
Avoid didanosine (ddI) plus stavudine (d4T) as serious toxicity including pancreatitis, neuropathy, and hepatitis can occur; fatal and nonfatal pancreatitis has been reported, and patients require careful assessment for pancreatitis, lactic acidosis, and hepatitis. 1
Avoid indinavir (IDV) in patients with renal impairment due to risk of nephrolithiasis and in those with hepatic impairment due to hyperbilirubinemia. 1
TDF-based regimens should be avoided when TAF-based options are available in patients with any degree of renal impairment. 1, 2
Timing and Adherence Considerations
PEP must be initiated as soon as possible, ideally within 1-2 hours but no later than 72 hours post-exposure, regardless of organ dysfunction status. 2, 3
Do not delay PEP initiation while awaiting detailed organ function results; start with the safest regimen (BIC/FTC/TAF) and adjust if necessary based on laboratory results. 2, 3
The full 28-day course must be completed regardless of subsequent information about the source patient, as incomplete adherence significantly reduces effectiveness. 2, 3
If toxicity develops during PEP, modification of the regimen should be considered after expert consultation rather than discontinuation; symptoms like nausea and diarrhea can often be managed with antimotility and antiemetic agents without changing the regimen. 1
Expert Consultation Triggers
Contact the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 888-448-4911 for complex cases involving severe organ dysfunction, known drug resistance, pregnancy, or delayed presentation, but do not delay PEP initiation while awaiting consultation. 2, 3
Seek consultation with clinicians experienced in antiretroviral therapy for patients with Child-Pugh class B or C cirrhosis or those with HBV/HCV co-infection on DAAs. 1
Common Pitfalls to Avoid
Never delay PEP initiation to obtain complete organ function testing; start immediately with the safest available regimen. 2, 3
Do not use older regimens (zidovudine-based, stavudine-based, or protease inhibitor-based) when modern integrase inhibitor-based regimens with better safety profiles are available. 1, 2
Do not discontinue PEP prematurely due to mild adverse effects; manage symptoms supportively and consider regimen modification only after expert consultation. 1, 2
For patients with HBV co-infection receiving tenofovir/emtricitabine-containing regimens, ensure close monitoring when stopping these agents, as elevation in liver transaminases can occur and HBV reactivation is possible. 1