What are the first line three-drug regimens for a patient with Human Immunodeficiency Virus (HIV)?

First-Line Three-Drug Regimens for HIV Treatment

Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) is the preferred first-line three-drug regimen for most treatment-naive adults with HIV-1 infection. 1, 2

Generally Recommended Initial Three-Drug Regimens

The following integrase strand transfer inhibitor (InSTI)-based regimens are recommended as first-line therapy, listed in order of preference:

Top-Tier Regimens

• Bictegravir/TAF/emtricitabine (BIC/TAF/FTC) - Single-tablet regimen with high efficacy, favorable side effect profile, and high barrier to resistance 1, 2, 3
• Dolutegravir plus TAF/emtricitabine (DTG + TAF/FTC) - Highly effective with strong resistance profile 1, 2
• Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) - Effective single-tablet regimen, but requires HLA-B*5701 testing before use to prevent hypersensitivity reactions 1, 2

Alternative Three-Drug Regimens When First-Line Options Are Unavailable

• Darunavir/cobicistat plus TAF/emtricitabine - Recommended when InSTI resistance is suspected, particularly after exposure to long-acting cabotegravir as PrEP 1, 2
• Darunavir boosted with ritonavir plus TAF/emtricitabine - Alternative protease inhibitor-based option 1
• Raltegravir plus TAF/emtricitabine - InSTI-based alternative 1
• Elvitegravir/cobicistat/TAF/emtricitabine - Single-tablet InSTI regimen 1

Critical Pre-Treatment Testing Requirements

Before initiating therapy, obtain the following tests (treatment may start before results return, except for HLA-B*5701):

• HLA-B*5701 testing is mandatory before prescribing any abacavir-containing regimen - Patients who test positive must never receive abacavir due to risk of potentially life-threatening hypersensitivity reactions 1, 2
• HIV-1 RNA level and CD4+ cell count 1
• HIV genotype for NRTI, NNRTI, and PI resistance 1
• Hepatitis B and C screening 1
• Renal function (estimated glomerular filtration rate) 1
• Baseline lipid panel and liver function tests 1

Special Population Considerations

Renal Impairment

• Avoid TDF-containing regimens in patients with or at risk for kidney disease - Use TAF instead, which has significantly less renal toxicity 1, 2
• TAF has minimal effect on proximal tubular function and proteinuria compared to TDF 1

Bone Disease

• Prefer TAF over TDF in patients with osteopenia or osteoporosis - TAF has little to no effect on bone mineral density 1, 2

Hepatitis B Coinfection

• Use regimens containing TAF or TDF plus emtricitabine or lamivudine - These provide dual activity against HIV and HBV 1, 2
• Do not use DTG/3TC (two-drug regimen) in HBV coinfection 1, 2

Pregnancy

• Dolutegravir plus TAF/emtricitabine is the recommended regimen during pregnancy 1, 2
• BIC/TAF/FTC is an alternative option 1
• Raltegravir is also recommended for use during pregnancy 1
• Cobicistat-boosted regimens should not be used during pregnancy due to inadequate drug levels 1

Tuberculosis Treatment

• Dolutegravir 50 mg twice daily plus TXF/XTC is recommended during active TB treatment with rifamycin-containing regimens 1
• BIC/TAF/FTC and DTG/3TC are not currently recommended with rifampin due to drug interactions 1

Efficacy Data

The evidence supporting these regimens is robust:

• BIC/TAF/FTC maintains virologic suppression (HIV-1 RNA <50 copies/mL) in 98.6% of patients through 5 years with no treatment-emergent resistance 4
• In pediatric populations aged 6-18 years, BIC/TAF/FTC maintained 98% virologic suppression at 48 weeks 5
• Real-world data from the BICSTaR study showed 94% of treatment-naive patients and 97% of treatment-experienced patients achieved undetectable viral load at 1 year 6

Safety and Tolerability Profile

Common Adverse Effects

• Weight gain averages 1.8-6.1 kg over 48-240 weeks with BIC/TAF/FTC, though BMI typically remains within healthy range 4, 7
• Lipid changes: Total cholesterol increases modestly (median 21 mg/dL), but total cholesterol:HDL ratio remains stable 4
• Drug discontinuation due to adverse events is rare (1.6% over 5 years with BIC/TAF/FTC) 4

Metabolic Considerations

• TAF reduces lipids less than TDF but does not adversely affect the total:HDL cholesterol ratio 1
• No cases of clinical renal disease have been directly attributed to TAF 1

Critical Pitfalls to Avoid

1. Never prescribe abacavir without confirmed negative HLA-B*5701 testing - This can cause life-threatening hypersensitivity reactions 1, 2

2. Do not use NNRTIs or abacavir for rapid ART start - These require specific testing results before initiation 1

3. Avoid cobicistat-boosted regimens during pregnancy - Drug levels are inadequate 1

4. Do not overlook drug-drug interactions - Particularly with cobicistat-boosted regimens and rifampin 1, 2

5. Never delay ART initiation - Treatment should begin as soon as possible after diagnosis, even on the same day if the patient is ready 1, 2

Monitoring After Initiation

• Measure HIV-1 RNA at 4-6 weeks to assess initial virologic response 2
• Continue viral load monitoring every 3 months until suppression is achieved and maintained for at least 1 year 2
• After 1 year of sustained suppression, monitoring can be reduced to every 6 months 2
• Monitor renal function (eGFR, urinalysis, proteinuria) every 6 months once HIV RNA is stable 1
• Assess CD4+ count at baseline and periodically; mean increases of 338 cells/μL are expected over 5 years 4