Recommended Initial Regimens for HIV Treatment
The recommended initial regimens for HIV treatment are integrase strand transfer inhibitor (InSTI)-based combinations, with bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) being the preferred first-line regimen for most patients due to its high efficacy, favorable side effect profile, and high barrier to resistance. 1, 2
First-Line Regimens (in order of preference)
Preferred Regimens
- Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - Single-tablet regimen with high efficacy, excellent tolerability, and high barrier to resistance 2, 3
- Dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) - Highly effective combination with strong resistance profile 2, 1
- Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) - Effective regimen but requires HLA-B*5701 testing before use to prevent hypersensitivity reactions 2, 1
Alternative Regimens
- Dolutegravir/lamivudine (DTG/3TC) - Two-drug regimen recommended only if HIV RNA level is <500,000 copies/mL, no lamivudine resistance, and no HBV co-infection 2, 4
- Darunavir (boosted with ritonavir or cobicistat) plus TAF/FTC - Recommended when InSTI resistance is suspected, particularly after exposure to long-acting cabotegravir as PrEP 2
- Elvitegravir/cobicistat/TAF/FTC - Effective but has more drug interactions due to cobicistat booster 2, 1
- Rilpivirine/TAF/FTC - Only for patients with pretreatment HIV RNA <100,000 copies/mL and CD4 count >200/μL 2, 5
Key Considerations for Regimen Selection
Patient-Specific Factors
- Viral load and CD4 count: DTG/3TC should not be used if HIV RNA ≥500,000 copies/mL or CD4 <200/μL 2
- Comorbidities:
- Hepatitis B co-infection: Must use regimens containing TAF or TDF plus FTC or 3TC (avoid DTG/3TC) 2, 1
- Pregnancy: DTG plus TAF/FTC is the recommended regimen; BIC/TAF/FTC is an alternative 2
Drug-Specific Considerations
- HLA-B*5701 testing: Mandatory before using abacavir to prevent potentially life-threatening hypersensitivity reactions 2, 1
- Drug interactions:
Efficacy and Safety Data
Efficacy
- BIC/TAF/FTC demonstrated 98.6% virologic suppression (HIV-1 RNA <50 copies/mL) through 5 years of follow-up with no treatment-emergent resistance 6
- DTG-based regimens show similar high rates of virologic suppression to BIC-based regimens 3, 6
- DTG/3TC demonstrated non-inferiority to 3-drug regimens but should only be used in specific patient populations 2
Safety
- TAF has fewer renal and bone toxicities compared to TDF, especially when used with pharmacological boosters 1, 7
- Weight gain is a consideration with InSTI-based regimens, with median weight increase of 6.1 kg over 5 years reported with BIC/TAF/FTC 6
- BIC/TAF/FTC has demonstrated minimal impact on bone mineral density (≤0.6% change) over 5 years 6
Common Pitfalls to Avoid
- Not testing for HLA-B*5701 before prescribing abacavir-containing regimens, which can lead to potentially life-threatening hypersensitivity reactions 2, 1
- Starting DTG/3TC without confirming HIV RNA level, resistance status, and HBV status 2
- Overlooking drug interactions, particularly with cobicistat-boosted regimens or in patients taking rifampin 2, 1
- Delaying ART initiation, which can lead to poorer outcomes; treatment should be started as soon as possible after diagnosis 1, 4
Monitoring After Initiation
- Measure viral load 4-6 weeks after starting ART to assess initial response 4
- Once viral suppression is achieved, monitor every 3 months until suppression is maintained for at least 1 year 4
- After 1 year of viral suppression, monitoring can be reduced to every 6 months 4
- Regularly assess for drug-specific toxicities and adherence 1