What is the latest recommended treatment for Human Immunodeficiency Virus (HIV) infection?

Latest Recommended Treatment for HIV Infection

Start antiretroviral therapy (ART) immediately upon HIV diagnosis—ideally within 7 days or even at the first clinic visit—using an integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) as the first-line regimen. 1, 2

Preferred First-Line Regimens

The most current guidelines prioritize InSTI-based combinations due to their superior efficacy, high barrier to resistance, and favorable tolerability profile:

Top-Tier Single-Tablet Regimens

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC): This is a preferred option with the highest evidence rating (AIa) 1, 2. Bictegravir requires no pharmacologic boosting, has minimal drug interactions, and demonstrates no emergence of resistant virus in treatment-naïve patients 2.

• Dolutegravir-based regimens: Multiple formulations are recommended with AIa evidence ratings 1, 2:

  • Dolutegravir + tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) + emtricitabine or lamivudine 1
  • Dolutegravir/abacavir/lamivudine (requires HLA-B*5701 testing before initiation to prevent hypersensitivity reactions) 1, 2

NRTI Backbone Selection

Choose tenofovir alafenamide (TAF) over tenofovir disoproxil fumarate (TDF) when possible, particularly for patients with or at risk for kidney disease, bone disease, or osteoporosis 2. TAF achieves higher intracellular concentrations with lower plasma levels, resulting in similar virologic efficacy but improved renal and bone safety 2.

• TAF-based backbones: Preferred for most patients due to better safety profile 2
• TDF-based backbones: Acceptable alternative but requires renal monitoring; avoid in patients with creatinine clearance <60 mL/min 2, 3
• Abacavir/lamivudine: Alternative option but mandatory HLA-B*5701 testing required before use; avoid in hepatitis B co-infection as abacavir lacks activity against HBV 2

The TLD Regimen (Tenofovir/Lamivudine/Dolutegravir)

This fixed-dose combination is widely used globally, particularly in resource-limited settings 1:

• Composition: TDF 300 mg + lamivudine 300 mg + dolutegravir 50 mg as a single daily pill 1
• Key advantages: Single-pill regimen enhancing adherence, high barrier to resistance, cost-effectiveness 1
• Critical caveats:
  • Avoid TDF component in patients with kidney disease or bone disease 1
  • Screen for hepatitis B before initiation 1
  • For pregnant women, dolutegravir is recommended (evidence rating AIb) combined with tenofovir/emtricitabine or lamivudine 1

Alternative Regimens (When InSTIs Cannot Be Used)

If InSTI-based regimens are contraindicated or unavailable:

• Boosted protease inhibitors (PIs): Darunavir/ritonavir + 2 NRTIs is effective but has more side effects and drug interactions 2
• NNRTIs: Rilpivirine or efavirenz + 2 NRTIs, though these have more adverse effects than InSTI-based regimens 4, 2
  • Rilpivirine restrictions: Only use if baseline HIV RNA <100,000 copies/mL and CD4 >200/μL; must be taken with food (≥390 calories); avoid with proton-pump inhibitors 4, 2
  • Efavirenz: Avoid in patients with depression history due to neuropsychiatric effects and increased suicidality risk 4

Emerging Treatment Options

• Long-acting injectables: Cabotegravir (InSTI) + rilpivirine administered intramuscularly every 4-8 weeks for maintenance therapy in virologically suppressed patients 4, 2
• Two-drug regimens: For virologically suppressed patients switching therapy, options include dolutegravir/rilpivirine, dolutegravir/lamivudine, or boosted PI/lamivudine (all with AIa evidence ratings) 4

Special Timing Considerations

Do not delay ART for most opportunistic infections—start within 2 weeks 1:

• Tuberculosis co-infection:

  • If CD4 ≥50/μL: Start ART within 2-8 weeks of TB treatment 1
  • If CD4 <50/μL: Start ART within 2 weeks of TB treatment 1

• Cryptococcal meningitis: Delay ART for 2-4 weeks after starting antifungal therapy; consider 2-week initiation if clinically improved with controlled intracranial pressure 1

Essential Pre-Treatment Testing

Before initiating ART, obtain 4:

• HIV RNA level (viral load)
• CD4 cell count
• HIV genotype resistance testing (reverse transcriptase and protease)
• HLA-B*5701 (if considering abacavir)
• Hepatitis B surface antigen
• Hepatitis C antibody
• Serum creatinine and estimated creatinine clearance
• Screening for sexually transmitted infections and tuberculosis

Monitoring During Treatment

• HIV RNA level: Within 6 weeks of starting ART, then every 3 months until <50 copies/mL for 1 year, then every 6 months 4, 2
• CD4 cell count: Every 6 months until >250/μL for 1 year, then can stop if virus remains suppressed 4
• Renal function: At first quarterly visit and annually thereafter; every 3-6 months for patients at risk for kidney injury 2

Critical Pitfalls to Avoid

1. Never use monotherapy or add a single drug to a failing regimen—this promotes resistance 4
2. Never start NNRTI-based regimens without baseline resistance testing—transmitted NNRTI resistance is common 4
3. Never initiate abacavir without HLA-B*5701 testing—risk of life-threatening hypersensitivity reaction 4, 2
4. Never use rilpivirine in patients with high viral loads (>100,000 copies/mL) or low CD4 counts (<200/μL)—increased risk of virologic failure 4
5. Screen for hepatitis B before starting or stopping tenofovir—severe HBV exacerbations can occur upon discontinuation 3

Expected Outcomes

With modern ART regimens and adherence, survival rates among HIV-infected adults retained in care approach those of uninfected adults 1, 5. Current regimens achieve durable viral suppression, prevent disease progression, and eliminate HIV transmission risk when viral load remains undetectable 5.