What is the recommended initial medication regimen for a patient with Human Immunodeficiency Virus (HIV)?

Initial Antiretroviral Therapy for HIV

Start antiretroviral therapy (ART) immediately upon HIV diagnosis for all patients, regardless of CD4 count, using an integrase strand transfer inhibitor (InSTI)-based regimen as first-line treatment. 1, 2

When to Initiate Treatment

• Begin ART as soon as possible after diagnosis, including at the first clinic visit if the patient is ready to commit to treatment 1
• Treatment should be started regardless of CD4 cell count for all viremic patients with established HIV infection 1
• In acute HIV infection, initiate ART immediately 1
• Remove structural barriers that delay ART receipt to enable same-day treatment initiation when appropriate 1

The rationale for immediate treatment is compelling: HIV replicates at 1 to 10 billion viruses per day, causing ongoing inflammation associated with earlier onset of multiple comorbidities 3. Delaying treatment provides no benefit and likely causes significant long-term harm 3. Additionally, early treatment prevents HIV transmission to others 3.

Recommended First-Line Regimens

The preferred initial regimens are InSTI-based combinations 1, 2:

Primary Recommendations (listed alphabetically):

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - preferred for most patients due to high efficacy, favorable side effect profile, and high barrier to resistance 2
• Dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) - highly effective with strong resistance profile 1, 2
• Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) - requires HLA-B*5701 testing before use 1, 2
• Elvitegravir/cobicistat/TAF/emtricitabine 1
• Raltegravir plus TAF/emtricitabine 1

These InSTI-based regimens demonstrate superior efficacy and tolerability compared to older regimens 4, 5.

Alternative Regimens When InSTI Not an Option

If an InSTI cannot be used 1, 2:

• Darunavir (boosted with ritonavir or cobicistat) plus TAF/FTC or TDF/FTC - particularly useful when InSTI resistance is suspected, such as after exposure to long-acting cabotegravir as PrEP 1, 2
• Efavirenz/TDF/emtricitabine 1
• Rilpivirine/TAF (or TDF)/emtricitabine - only for patients with HIV RNA <100,000 copies/mL and CD4 >200/μL 1, 6

Critical Pre-Treatment Testing

Mandatory Testing:

• HLA-B*5701 must be performed before prescribing any abacavir-containing regimen 1, 2
• Those who test positive should never receive abacavir due to risk of potentially life-threatening hypersensitivity reactions 1, 2
• Resistance testing should be performed before starting therapy to guide regimen selection 7

Special Population Considerations

Pregnancy:

• Dolutegravir plus TAF/FTC is the recommended regimen during pregnancy 1, 2, 6
• Alternative options include atazanavir/ritonavir, darunavir/ritonavir, efavirenz, or raltegravir (all combined with TDF/FTC or TDF/3TC) 1
• HIV-infected pregnant women should initiate ART for their own health and to reduce transmission to the infant 1

Hepatitis B Co-infection:

• Use regimens containing tenofovir (TAF or TDF) plus lamivudine or emtricitabine 1, 2
• Avoid dolutegravir/lamivudine (DTG/3TC) two-drug regimen in HBV co-infection 2
• Entecavir may be used for HBV treatment but should be avoided if HIV RNA is not suppressed due to risk of HIV resistance 1

Hepatitis C Co-infection:

• Select ART regimens without significant drug interactions with HCV therapies 1

Tuberculosis Co-infection:

• Use dolutegravir 50 mg twice daily, efavirenz 600 mg daily, or raltegravir 800 mg twice daily plus 2 NRTIs when receiving rifamycin-based TB treatment 1, 6
• Bictegravir with rifampin is contraindicated due to drug interactions 1
• Boosted protease inhibitors should only be used if InSTI-based or efavirenz-based regimens are not options; consider substituting rifabutin for rifampin 1
• For TB with CD4 ≥50/μL, initiate ART within 2-8 weeks of starting TB treatment 1

Cryptococcal Meningitis:

• Delay ART initiation until 4-6 weeks after starting antifungal therapy 1

Renal Impairment:

• Avoid tenofovir disoproxil fumarate (TDF) in patients with or at risk for kidney disease, osteopenia, or osteoporosis 1, 2, 6
• TDF should be avoided or dose-adjusted when creatinine clearance is below 60 mL/min 1, 6
• Tenofovir alafenamide (TAF) is not recommended when creatinine clearance is below 30 mL/min 1
• TAF has fewer renal and bone toxicities compared to TDF, especially when used with pharmacological boosters 2
• Monitor renal function with estimated GFR, urinalysis, and testing for glycosuria and proteinuria at ART initiation/change and every 6 months 1

Bone Disease:

• Prefer TAF over TDF in patients with osteopenia or osteoporosis 1, 2

Two-Drug Regimens

• Dolutegravir/lamivudine (DTG/3TC) is only recommended when:
  • HIV RNA level is <500,000 copies/mL
  • No lamivudine resistance present
  • No hepatitis B co-infection 2
• Two-drug regimens should otherwise only be used in rare situations when patients cannot take abacavir, TAF, or TDF 1

Common Pitfalls to Avoid

• Never prescribe abacavir without HLA-B*5701 testing - this can cause life-threatening hypersensitivity reactions 1, 2
• Do not start DTG/3TC without confirming HIV RNA level, resistance status, and HBV status 2
• Do not overlook drug interactions, particularly with cobicistat-boosted regimens or in patients taking rifampin 2, 8
• Do not delay ART initiation - this leads to poorer outcomes and continued viral replication 1, 3
• Do not use rilpivirine in patients with HIV RNA >500,000 copies/mL or CD4 <200/μL 2, 6

Monitoring After Initiation

• Measure viral load 4-6 weeks after starting ART to assess initial response 2
• Once viral suppression is achieved, monitor every 3 months until suppression is maintained for at least 1 year 2
• After 1 year of viral suppression, monitoring can be reduced to every 6 months 2
• Regularly assess for drug-specific toxicities and adherence 2
• Monitor renal function every 6 months along with HIV RNA once stable 1

Rationale for Current Approach

The shift toward immediate treatment initiation and InSTI-based regimens reflects decades of evidence showing that: (1) unchecked viral replication causes inflammation and accelerates comorbidities 3, (2) modern medications are more efficacious and less toxic than older agents 4, 9, (3) treatment prevents transmission to others 3, and (4) waiting to treat provides no benefit while potentially causing harm 3. With life-long therapy expected, starting at CD4 732 versus 493 cells/μL makes little difference over a 40-50 year treatment course, but earlier treatment prevents irreversible damage 3.