What is the recommended first-line treatment for a patient with HIV-1 (Human Immunodeficiency Virus type 1) infection, considering Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) as an option?

Biktarvy for HIV-1 Treatment

First-Line Treatment Recommendation

Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) is a preferred first-line antiretroviral regimen for treatment-naïve adults and adolescents with HIV-1 infection. 1

Guideline-Based Recommendations

Generally Recommended Initial Regimens

The International Antiviral Society-USA Panel consistently lists Biktarvy among the top-tier options for initial HIV-1 treatment:

• Bictegravir/TAF/emtricitabine is classified as a "generally recommended initial regimen" with the highest evidence rating (AIa) 1
• This recommendation has been maintained across multiple guideline updates from 2018 through 2025 1
• The 2025 guidelines continue to endorse Biktarvy as a preferred option for treatment-naïve patients 1

FDA-Approved Indications

Biktarvy is FDA-approved as a complete regimen for HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history 2

The drug is also approved to replace current antiretroviral regimens in virologically suppressed patients (HIV-1 RNA <50 copies/mL) with no known resistance to bictegravir or tenofovir 2

Dosing and Administration

Standard Adult Dosing

• One tablet containing 50 mg bictegravir, 200 mg emtricitabine, and 25 mg tenofovir alafenamide taken once daily with or without food 2

Pediatric Dosing

• For patients weighing 14-25 kg: One tablet containing 30 mg bictegravir, 120 mg emtricitabine, and 15 mg tenofovir alafenamide once daily 2
• For patients weighing ≥25 kg: Adult dosing applies 2

Pregnancy Considerations

For pregnant individuals who are virologically suppressed on a stable regimen with no known resistance, Biktarvy can be continued at the standard adult dose 2

Pre-Treatment Testing Requirements

Before initiating Biktarvy, the following tests must be performed 2:

• Hepatitis B virus infection testing (due to risk of HBV exacerbation upon discontinuation)
• Serum creatinine and estimated creatinine clearance
• Urine glucose and urine protein
• Serum phosphorus in patients with chronic kidney disease

The 2018 IAS-USA guidelines recommend obtaining HIV-1 RNA level, CD4 count, and HIV genotype testing before starting therapy, though treatment may begin before results are available 1

Contraindications and Restrictions

Absolute Contraindications

Biktarvy must not be co-administered with dofetilide or rifampin 2

Renal Impairment Restrictions

• Not recommended for patients with estimated creatinine clearance 15 to <30 mL/min 2
• Not recommended for patients with creatinine clearance <15 mL/min who are not receiving chronic hemodialysis 2
• Not recommended for treatment-naïve patients with creatinine clearance <15 mL/min 2

Hepatic Impairment

Biktarvy is not recommended in patients with severe hepatic impairment 2

Clinical Efficacy Evidence

Treatment-Naïve Patients

At 96 weeks, Biktarvy demonstrated non-inferiority to dolutegravir/abacavir/lamivudine, with 88% achieving HIV-1 RNA <50 copies/mL versus 90% in the comparator arm 3

The regimen showed high efficacy with no emergent resistance through 96 weeks of follow-up 3

Virologically Suppressed Patients Switching Therapy

In patients switching from boosted protease inhibitor regimens, Biktarvy maintained virologic suppression with only 2% experiencing HIV-1 RNA ≥50 copies/mL at week 48, identical to those continuing their baseline regimen 4

Women-Specific Data

In a study of 470 virologically suppressed women, switching to Biktarvy was non-inferior to staying on baseline regimen, with 1.7% experiencing virologic failure in both arms at week 48 5

No treatment-emergent resistance developed in any participant receiving Biktarvy 5

Pediatric and Adolescent Data

In 100 virologically suppressed children and adolescents (ages 6-18 years), all maintained suppression at week 24, and 98% maintained suppression at week 48 6

The regimen was well tolerated with no treatment-emergent resistance 6

Advantages Over Alternative Regimens

Key Clinical Benefits

• Single-tablet, once-daily regimen improves adherence 1
• High genetic barrier to resistance 7, 3
• No treatment-emergent resistance observed in clinical trials through 96 weeks 3, 4
• Can be taken with or without food 2
• Fewer drug interactions compared to boosted protease inhibitors 1

Tolerability Profile

The most common adverse events are diarrhea, nausea, and headache (each occurring in ≥5% of patients) 2

Discontinuation rates due to adverse events are extremely low, with only 1% discontinuing in the phase 3 switching study 4

Important Safety Warnings

Hepatitis B Co-infection

Severe acute exacerbations of hepatitis B can occur upon discontinuation of Biktarvy in patients co-infected with HIV-1 and HBV 2

Close monitoring of hepatic function is required for several months after stopping therapy, and anti-hepatitis B therapy may be warranted 2

Renal Monitoring

New or worsening renal impairment can occur; assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein when initiating and during therapy 2

Also assess serum phosphorus in patients with chronic kidney disease 2

Immune Reconstitution Syndrome

Immune reconstitution syndrome may occur when starting Biktarvy, potentially unmasking hidden opportunistic infections 2

Lactic Acidosis Risk

Rare but serious lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues 2

Discontinue treatment if symptoms or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity 2

Comparison with Other Integrase Inhibitors

Bictegravir vs. Dolutegravir

While both are highly effective integrase inhibitors, the guidelines note that there are fewer long-term safety and efficacy data with bictegravir than with dolutegravir 1

However, bictegravir demonstrated non-inferiority to dolutegravir in head-to-head trials at 24 weeks and 96 weeks 7, 3

Resistance Barrier

Bictegravir has demonstrated the lowest risk of resistance with virologic failure among integrase inhibitors in comparative trials 1

Role in Post-Exposure Prophylaxis

The CDC recommends Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) as a preferred single-tablet regimen for HIV post-exposure prophylaxis in adults and adolescents 1, 8

This represents a convenient option as it provides all three required antiretroviral drugs in a single tablet 1, 8

Common Pitfalls to Avoid

Do Not Use as Monotherapy

Biktarvy is a complete regimen; do not co-administer with other antiretroviral medications for HIV-1 treatment 2

Resistance Testing Before Switching

When switching virologically suppressed patients to Biktarvy, ensure there are no known or suspected substitutions associated with resistance to bictegravir or tenofovir 2

HBV Co-infection Management

Never discontinue Biktarvy in HBV co-infected patients without ensuring alternative HBV suppressive therapy is in place 2

Drug Interaction Screening

Always screen for potential drug interactions, particularly with dofetilide (contraindicated) and rifampin (contraindicated) 2