What is the initial recommendation for Antiretroviral Therapy (ART) management of HIV/AIDS?

Initial Antiretroviral Therapy (ART) for HIV/AIDS

Start all HIV-infected patients with detectable viremia on ART immediately, regardless of CD4 count, using an integrase strand transfer inhibitor (InSTI)-based three-drug regimen as first-line therapy. 1, 2, 3

Preferred First-Line Regimens

The following regimens represent the optimal initial therapy for most treatment-naïve patients, listed in order of preference based on the most recent 2024-2025 guidelines:

Top-Tier Regimens (Strongest Evidence)

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - This is the preferred first-line regimen for most patients due to high efficacy, favorable side effect profile, high barrier to resistance, and single-tablet formulation 2, 3

• Dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) - Highly effective with strong resistance profile and no pharmacologic boosting required 1, 2, 3

• Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) - Effective single-tablet regimen, but requires mandatory HLA-B*5701 testing before initiation to prevent potentially life-threatening hypersensitivity reactions 1, 2

Alternative First-Line Regimens

When preferred regimens cannot be used, the 2020 International Antiviral Society-USA panel recommends these alternatives 4:

• Darunavir/cobicistat/tenofovir alafenamide/emtricitabine - For patients with known or suspected pre-therapy multidrug resistance 4
• Raltegravir plus tenofovir alafenamide/emtricitabine - For patients at high risk of drug-drug interactions 4
• Doravirine-based regimens - For patients intolerant to InSTIs 4

Two-Drug Regimen (Restricted Use)

• Dolutegravir/lamivudine (DTG/3TC) - Only use if HIV RNA <500,000 copies/mL, no lamivudine resistance documented, and no hepatitis B co-infection 2, 3

Critical Pre-Treatment Requirements

Before initiating ART, perform these mandatory tests 1, 3:

• HLA-B*5701 testing - Must be negative before prescribing any abacavir-containing regimen; approximately 50% of HLA-B*5701-positive individuals will experience life-threatening hypersensitivity reactions 1, 2
• HIV genotype resistance testing (baseline) 4, 1
• Hepatitis B and C serology 1, 3
• CD4+ cell count and HIV RNA viral load 1, 3
• Creatinine clearance and basic chemistry panel 1, 3
• Liver function tests 1, 3

Timing of ART Initiation

Initiate ART immediately at the first clinic visit after HIV diagnosis if the patient is ready to commit to treatment. 3 This includes same-day initiation in many centers 4. For acute HIV infection, immediate ART initiation is strongly recommended 4, 3.

The evidence is clear: early ART reduces AIDS-related events, non-AIDS-related events, all-cause mortality, and HIV transmission risk 4. Delaying therapy leads to poorer outcomes 1, 2.

Special Populations and Modifications

Renal Impairment

• Avoid tenofovir disoproxil fumarate (TDF)-containing regimens 2
• TAF has fewer renal toxicities than TDF, especially with pharmacologic boosters 1, 2
• Adjust dosing intervals for creatinine clearance <50 mL/min 5, 6

Hepatitis B Co-infection

• Must use regimens containing tenofovir (TAF or TDF) plus emtricitabine or lamivudine 2, 3
• Avoid DTG/3TC two-drug regimen 2
• Test all patients for chronic HBV before initiating ART 6

Pregnancy

• Dolutegravir plus TAF/FTC is the recommended regimen 2
• Bictegravir/TAF/FTC is an alternative 2
• Preliminary data have raised concerns about dolutegravir use in individuals capable of becoming pregnant, though it remains recommended 4

Tuberculosis Co-infection

• Efavirenz-based regimens are preferred due to rifampin compatibility 4
• Rifampin cannot be used with BIC/TAF/FTC, DTG/3TC, elvitegravir/cobicistat, or rilpivirine 2
• Initiate ART within 2-8 weeks of starting TB treatment if CD4 ≥50/μL 3

Opportunistic Infections

• For most OIs: initiate ART within 2 weeks of starting OI treatment 3
• Cryptococcal meningitis: delay ART for 2-4 weeks after starting antifungal therapy to reduce risk of immune reconstitution inflammatory syndrome 3

Suspected Drug Resistance

• Use darunavir (boosted with ritonavir or cobicistat) plus TAF/FTC when InSTI resistance is suspected, particularly after long-acting cabotegravir PrEP exposure 2

Monitoring After Initiation

Follow this specific monitoring schedule 2, 3:

• 4-6 weeks: Measure viral load to assess initial response
• Every 3 months: Continue monitoring until viral suppression maintained for ≥1 year
• Every 6 months: After 1 year of sustained viral suppression
• Regularly assess for drug-specific toxicities and adherence at each visit 1, 2

Common Pitfalls to Avoid

1. Not testing for HLA-B*5701 before prescribing abacavir - This can result in potentially fatal hypersensitivity reactions 1, 2

2. Starting DTG/3TC without confirming eligibility - Must verify HIV RNA <500,000 copies/mL, no resistance, and no HBV co-infection 2

3. Overlooking drug interactions with cobicistat-boosted regimens - Cobicistat has extensive drug interactions that can lead to treatment failure or toxicity 2

4. Delaying ART initiation - Every delay worsens outcomes and increases transmission risk 1, 2, 3

5. Discontinuing tenofovir in HBV co-infected patients - This can cause severe hepatitis B exacerbations, liver decompensation, and liver failure 5, 6

6. Using rilpivirine inappropriately - Only use if baseline HIV RNA <100,000 copies/mL and CD4 >200/μL; requires food and stomach acidity for absorption 4

7. Ignoring renal function monitoring - Tenofovir can cause acute renal failure and Fanconi syndrome; monitor creatinine clearance, urine glucose, and urine protein regularly 6

Why InSTI-Based Regimens Are Preferred

InSTI-based regimens (bictegravir, dolutegravir) have become the standard of care because they 4, 1, 2:

• Achieve higher rates of virologic suppression compared to other drug classes
• Have high barriers to resistance
• Do not require pharmacologic boosting (avoiding cobicistat/ritonavir drug interactions)
• Offer convenient single-tablet formulations
• Have favorable tolerability profiles with fewer central nervous system and metabolic adverse effects than older regimens

The shift toward these regimens is evidence-based: by 2007,85% of patients at major HIV centers were receiving the same first-line regimen, reflecting the clear superiority of modern combination therapy 7.