What once‑daily, single‑tablet antiretroviral regimen should be prescribed for a patient with HIV and chronic hepatitis B, considering a possible estimated glomerular filtration rate less than 60 mL/min, severe osteoporosis, or any contraindication to tenofovir alafenamide?

Recommended Antiretroviral Regimen for HIV/HBV Co-infection with Renal or Bone Contraindications to TAF

For a patient with HIV and chronic hepatitis B who has eGFR <60 mL/min, severe osteoporosis, or any contraindication to tenofovir alafenamide, prescribe dolutegravir 50 mg plus lamivudine 300 mg once daily as a two-drug regimen. 1

Rationale for This Recommendation

Why This Specific Regimen

• Dolutegravir/lamivudine is the only recommended once-daily, single-tablet regimen that maintains both HIV and HBV suppression without requiring tenofovir. 1 This two-drug combination is specifically recommended for virologically suppressed patients and has demonstrated efficacy in maintaining viral suppression. 1

• Lamivudine (or emtricitabine) is essential for HBV suppression when tenofovir cannot be used. 1 Patients with HIV/HBV co-infection must continue taking either tenofovir or lamivudine/emtricitabine to prevent HBV reactivation and potential hepatic decompensation. 1, 2

Why Standard Regimens Are Contraindicated

• Bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) is contraindicated because TAF cannot be used when creatinine clearance is below 30 mL/min. 1, 3 While Biktarvy can be used in patients with creatinine clearance ≥30 mL/min 3, it is not recommended for those with severe osteoporosis, and your patient has either eGFR <60 mL/min or severe osteoporosis as stated contraindications.

• Tenofovir disoproxil fumarate (TDF) is absolutely contraindicated in patients with osteoporosis or osteopenia 1 and should be avoided or dose-adjusted when creatinine clearance falls below 60 mL/min. 1

• TAF is not recommended when creatinine clearance is below 30 mL/min 1, making it unsuitable for patients with significant renal impairment.

Dosing Adjustments for Renal Impairment

• Lamivudine requires dose reduction when creatinine clearance falls below 50 mL/min/1.73 m². 1 The standard dose is 300 mg once daily, but this must be adjusted based on the specific creatinine clearance level.

• Dolutegravir does not require dose adjustment for renal impairment and can be safely used even in severe hepatic impairment. 1

• Most fixed-dose combination tablets are contraindicated when eGFR falls below 50 mL/min/1.73 m², requiring individual component dosing. 1

Critical Monitoring Requirements

Hepatitis B Monitoring

• Never discontinue lamivudine without alternative HBV suppressive therapy, as this can precipitate severe hepatitis flare or hepatic decompensation. 1, 2 This is a life-threatening complication that requires careful management.

• If switching from a tenofovir-containing regimen to dolutegravir/lamivudine, ensure continuous HBV suppression by not creating a gap in therapy. 1

HIV Monitoring

• Measure HIV-1 RNA at 1 month after initiating or switching regimens, then every 3-6 months once stable. 3

• Review resistance testing history before prescribing dolutegravir/lamivudine to ensure both agents are fully active. 1 This two-drug regimen should only be used when both components have full activity.

Renal Function Monitoring

• Monitor serum creatinine and estimated glomerular filtration rate at baseline, 1 month, then every 3-6 months. 1, 2

• If renal function continues to decline, consider alternative HBV therapy such as entecavir (though this can select for HIV resistance if HIV is not fully suppressed). 1

Important Clinical Caveats

When This Regimen May Not Be Appropriate

• Dolutegravir/lamivudine is not recommended for patients with archived M184V/I resistance mutations detected on previous genotypic testing, as lamivudine will not be fully active. 1

• This two-drug regimen requires documented viral suppression before switching; it is not typically used as initial therapy in treatment-naive patients with HBV co-infection. 1

• If the patient has active opportunistic infections, an integrase inhibitor-based three-drug regimen may be preferred initially. 1

Alternative Considerations

• If eGFR is between 30-60 mL/min and osteoporosis is the primary concern (not severe renal impairment), TAF-based regimens may still be considered with careful monitoring. 1 However, given the question specifies "any contraindication to TAF," dolutegravir/lamivudine remains the safest choice.

• For patients requiring tuberculosis treatment, dolutegravir dosing must be increased to 50 mg twice daily when co-administered with rifampin. 1

Weight and Metabolic Monitoring

• Monitor for weight gain, as integrase inhibitor-based regimens including dolutegravir have been associated with modest weight increases. 4 However, this typically remains within healthy BMI ranges. 4