What is the recommended dosage and treatment plan for Delstrigo (doravirine, lamivudine, and tenofovir disoproxil fumarate) in adults with HIV-1 infection?

Delstrigo Dosing and Treatment Plan for HIV-1 Infection in Adults

Delstrigo should be administered as one tablet taken orally once daily, with or without food, in adults and pediatric patients weighing at least 35 kg who are either treatment-naïve or virologically suppressed with no history of treatment failure or resistance to its components. 1

Recommended Dosage

• One tablet once daily containing doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg 1
• Can be taken with or without food—food has no clinically meaningful effect on doravirine bioavailability 1, 2
• No pharmacokinetic interactions occur between the three components when co-administered 3

Patient Eligibility Criteria

Delstrigo is indicated for two specific populations 1:

• Treatment-naïve adults with no prior antiretroviral therapy history
• Virologically suppressed patients (HIV-1 RNA <50 copies/mL) on a stable regimen with no history of treatment failure and no known resistance mutations to doravirine, lamivudine, or tenofovir disoproxil fumarate

Critical Pre-Treatment Testing Requirements

Before initiating Delstrigo, obtain 1:

• Hepatitis B surface antigen (HBsAg) testing—mandatory due to risk of severe hepatitis B exacerbation upon discontinuation
• Serum creatinine and estimated creatinine clearance—do not initiate if CrCl <50 mL/min
• Urine glucose and urine protein
• Serum phosphorus in patients with chronic kidney disease
• HIV genotype testing for NRTI, NNRTI resistance if not treatment-naïve 4

Absolute Contraindications

Do not prescribe Delstrigo if 1:

• Estimated creatinine clearance <50 mL/min—this is a fixed-dose combination where individual components cannot be adjusted
• Co-administration with strong CYP3A inducers including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, or St. John's wort—these significantly decrease doravirine concentrations and reduce effectiveness
• Previous hypersensitivity reaction to lamivudine

Special Dosing Adjustment with Rifabutin

If rifabutin co-administration is necessary 1:

• Take one Delstrigo tablet once daily
• Add one additional doravirine 100 mg tablet (PIFELTRO) approximately 12 hours after Delstrigo for the duration of rifabutin co-administration

Ongoing Monitoring Schedule

Every 3 months 1:

• Serum creatinine and estimated creatinine clearance (on clinically appropriate schedule)
• Urine glucose and urine protein

Every 6-12 months 1:

• Serum phosphorus in patients with chronic kidney disease

Critical Safety Warning: Hepatitis B Co-infection

Severe acute exacerbations of hepatitis B (including liver decompensation and liver failure) have been reported in HIV/HBV co-infected patients who discontinue lamivudine or tenofovir-containing products 1:

• Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after discontinuing Delstrigo in co-infected patients
• Consider initiating anti-hepatitis B therapy if appropriate upon discontinuation 1
• Patients with cirrhosis are at particularly high risk 5

Severe Skin Reaction Warning

Discontinue Delstrigo immediately if 1:

• Painful rash with mucosal involvement develops
• Progressive severe rash develops
• Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected

Position in Treatment Guidelines

While Delstrigo is FDA-approved, it is not listed among the generally recommended initial regimens in the 2018 International Antiviral Society-USA guidelines 4. The preferred first-line regimens are integrase strand transfer inhibitor (INSTI)-based combinations including bictegravir/TAF/emtricitabine, dolutegravir/abacavir/lamivudine, or dolutegravir plus TAF/emtricitabine 4, 5.

Delstrigo may be considered as an alternative when generally recommended regimens are not available or not an option, particularly given that efavirenz/TDF/emtricitabine (another NNRTI-based regimen) remains a recommended alternative 4. However, note that NNRTIs should not be used for rapid ART start on the same day as HIV diagnosis 4.

Clinical Efficacy Data

In the DRIVE-SHIFT trial, switching virologically suppressed patients to Delstrigo maintained viral suppression 6:

• 90.8% maintained HIV-1 RNA <50 copies/mL at week 48 after switching to Delstrigo
• Demonstrated noninferiority compared to continuing baseline regimen
• Patients switching from ritonavir-boosted protease inhibitors experienced significant reductions in LDL-C and non-HDL-C 6

Resistance emergence is rare (<2%) in treatment-naïve individuals, and Delstrigo remains active against K103N viruses, the most prevalent NNRTI resistance mutation 7.