What is the recommended initial antiretroviral therapy for a 6-year-old patient weighing 22 kg, who is HLA-B*5701 (Human Leukocyte Antigen B*5701) positive and can swallow tablets?

Recommended Antiretroviral Regimen for HLA-B*5701 Positive 6-Year-Old

The correct answer is B) Bictegravir/emtricitabine/tenofovir alafenamide 30/120/15mg once daily, as this patient is HLA-B*5701 positive and therefore must avoid all abacavir-containing regimens due to the risk of potentially life-threatening hypersensitivity reactions. 1

Critical Contraindication: Abacavir and HLA-B*5701

• Patients who test positive for HLA-B*5701 should not be given abacavir under any circumstances (evidence rating AIa), as approximately half of HLA-B*5701 positive individuals will experience a potentially life-threatening hypersensitivity reaction to abacavir 1

• This absolute contraindication immediately eliminates options A and D, both of which contain abacavir 1

• The hypersensitivity reaction can be fatal, particularly upon rechallenge with abacavir, making this contraindication non-negotiable 2, 3

• This information must be documented prominently in the medical record to prevent future inadvertent abacavir exposure 1

Pediatric Dosing Considerations

Weight-Based Formulation Selection

• For this 22 kg patient, the pediatric formulation of bictegravir/emtricitabine/tenofovir alafenamide (30/120/15mg) is specifically indicated for children weighing 14 kg to less than 25 kg 4

• The adult dose formulation (50/200/25mg) is only recommended for patients weighing at least 25 kg, making option C inappropriate for this patient's weight 4

• Bictegravir is approved for pediatric patients weighing at least 14 kg as part of a complete regimen for HIV-1 treatment 5, 4

Tablet Administration

• Since this patient can easily swallow tablets, the standard tablet formulation is appropriate 4

• For children unable to swallow whole tablets, the 30/120/15mg formulation can be split, with each part taken separately within approximately 10 minutes 4

Why Bictegravir-Based Regimen is Optimal

First-Line Recommendation

• Integrase strand transfer inhibitor (InSTI)-based regimens are the optimal initial therapy for HIV treatment, with bictegravir being a preferred InSTI due to its high barrier to resistance and low pill burden 5

• Bictegravir-based regimens are recommended as first-line therapy with approval in 2018 as part of a complete regimen for HIV-1 treatment 5

• Bictegravir does not require pharmacologic boosting, has a high barrier to resistance, and is associated with low pill burden and toxicity 5

Tenofovir Alafenamide (TAF) Backbone

• TAF results in lower plasma levels of tenofovir and higher intracellular concentration compared to TDF, with similar virologic efficacy 1, 5

• TAF has fewer tenofovir-associated toxic effects, including less proximal renal tubular toxicity and smaller reductions in bone mineral density compared to TDF 1

• The combination of bictegravir with TAF/emtricitabine has shown 92.4% virologic suppression rate at 48 weeks in clinical trials 6

Why Other Options Are Incorrect

Option A (Abacavir/dolutegravir/lamivudine 600/50/300mg)

• Absolutely contraindicated due to abacavir content in an HLA-B*5701 positive patient 1

• Additionally, this adult dose formulation is inappropriate for a 22 kg pediatric patient 4

Option C (Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 150/150/200/10mg)

• While this is an acceptable InSTI-based regimen, the dosing is inappropriate for a 22 kg patient 4

• Elvitegravir regimens have a lower barrier to resistance compared to bictegravir and include cobicistat, which results in more drug interactions 1

• This formulation is designed for adults and larger pediatric patients weighing at least 25 kg 4

Option D (Abacavir/dolutegravir/lamivudine dispersible tablets)

• Absolutely contraindicated due to abacavir content in an HLA-B*5701 positive patient 1

• The dispersible formulation is unnecessary since this patient can swallow tablets 4

Important Clinical Considerations

Baseline and Monitoring Requirements

• Prior to initiating bictegravir/emtricitabine/tenofovir alafenamide, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein 4

• This regimen requires an estimated creatinine clearance greater than or equal to 30 mL/min for pediatric patients 4

• HIV RNA level testing should be performed within 6 weeks of starting antiretroviral therapy, then every 3 months until viral load is <50 copies/mL for 1 year, then every 6 months 5

Hepatitis B Coinfection Screening

• Test for hepatitis B virus infection before or when initiating therapy, as severe acute exacerbations of hepatitis B can occur upon discontinuation of emtricitabine/tenofovir-containing regimens 4

Administration Details

• Bictegravir/emtricitabine/tenofovir alafenamide can be taken once daily with or without food 4

• The regimen is contraindicated with rifampin due to decreased bictegravir plasma concentrations 4