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

HIV Treatment

All HIV-infected individuals with detectable plasma virus should receive antiretroviral therapy (ART) immediately, regardless of CD4 count, using an integrase strand transfer inhibitor (INSTI)-based regimen as first-line treatment. 1

Recommended Initial Regimens for Treatment-Naive Patients

The optimal first-line regimens consist of an INSTI plus two nucleoside reverse transcriptase inhibitors (NRTIs), listed in order of preference:

Preferred INSTI-Based Regimens

• Dolutegravir/abacavir/lamivudine (single-tablet regimen) 1
• Dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine 1
• Bictegravir/emtricitabine/TAF (single-tablet regimen) 1
• Elvitegravir/cobicistat/TAF/emtricitabine (single-tablet regimen) 1
• Raltegravir plus TAF/emtricitabine 1

Critical Pre-Treatment Requirements

• HLA-B*5701 testing is mandatory before prescribing abacavir - those who test positive must never receive abacavir due to risk of life-threatening hypersensitivity reaction 1
• Combined HIV antibody and antigen testing (or HIV RNA if acute infection suspected) 1
• Baseline resistance testing (genotype) before initiating therapy 2
• Hepatitis B and C screening 1
• Renal function assessment (serum creatinine) 1, 2

Alternative Regimens When INSTI Not an Option

If an INSTI cannot be used, the following are acceptable alternatives:

• Darunavir (boosted with ritonavir or cobicistat) plus TAF/emtricitabine or abacavir/lamivudine 1
• Efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine 1
• Rilpivirine/TAF/emtricitabine 1

Key Principles for Successful Treatment

When to Start

• Initiate ART as soon as possible after HIV diagnosis, ideally on the same day 1
• Treatment is recommended for all viremic patients regardless of CD4 count 1, 3
• In acute HIV infection, start immediately to reduce reservoir size and immune activation 1

Treatment Goals

• The primary objective is achieving undetectable viral load (HIV RNA <50 copies/mL) 1, 3
• Check HIV RNA at 2-4 weeks to confirm early virologic response 4, 5
• Goal is undetectable viral load by 12-24 weeks from ART initiation 4, 5
• Once suppressed, monitor viral load every 3-6 months 2

Critical Pitfalls to Avoid

• Never use monotherapy - boosted protease inhibitor or dolutegravir monotherapy is explicitly not recommended 1
• Never add a single active agent to a failing regimen - this guarantees further resistance development 1, 4, 5
• Avoid tenofovir disoproxil fumarate (TDF) in patients with kidney disease or osteoporosis - use TAF instead 1
• Never discontinue therapy once started - planned treatment interruptions are not recommended outside research settings 1

Management of Virological Failure

Virological failure is defined as HIV RNA >200 copies/mL on two consecutive measurements 1, 5

Immediate Steps

• Obtain resistance testing while patient is still taking the failing regimen (or within 4 weeks of stopping) 1, 5
• Confirm true virological failure with repeat testing 5, 2
• Assess adherence thoroughly - this is the most common cause of treatment failure 5, 2
• Review all historical resistance data from prior genotypes 5

Salvage Regimens Based on Failing Drug Class

After NNRTI failure:

• Dolutegravir plus 2 NRTIs (with ≥1 active drug by genotype) 1, 2

After INSTI failure:

• Boosted protease inhibitor plus 2 NRTIs (with ≥1 active NRTI) 1, 5, 2
• Options include darunavir/ritonavir or darunavir/cobicistat 5

After protease inhibitor failure:

• Virological failure with resistance is rare with PIs 1
• Focus on adherence support or switch to improve tolerability 1

For raltegravir or elvitegravir resistance:

• Dolutegravir 50 mg twice daily (not once daily) plus at least 1 fully active agent 1, 5

Multiclass Resistance (3-Class Failure)

When resistance exists to NRTIs, NNRTIs, and INSTIs/PIs, construct the next regimen using drugs from new classes:

• Fostemsavir (attachment inhibitor) with at least 1 additional active drug 1, 5
• Ibalizumab (CD4 monoclonal antibody) IV every 2 weeks with optimized background therapy 1, 5
• Lenacapavir (capsid inhibitor) with another fully active agent 5
• Expert consultation is essential for complex resistance patterns 5

Switching Regimens in Virologically Suppressed Patients

For patients with undetectable viral load who need to switch due to toxicity, intolerance, or preference:

Two-Drug Regimens (Appropriate for Simplification)

• Dolutegravir/rilpivirine 1
• Boosted protease inhibitor with lamivudine 1
• Dolutegravir/lamivudine 1
• Long-acting injectable cabotegravir/rilpivirine every 4-8 weeks 1

Critical requirement: Both agents must be fully active (no prior resistance) 1

Important Caution When Switching

• Never switch from a boosted PI to a drug with low genetic barrier (NNRTI or raltegravir) if NRTI resistance mutations are present 1
• Review co-medications to ensure no dosing adjustments needed 1

Special Populations and Considerations

Pregnancy

• HIV-infected pregnant women should initiate ART for their own health and to prevent transmission to the infant 1
• Dolutegravir-based regimens are preferred 4

Hepatitis B Co-infection

• Continue tenofovir-based therapy (TDF or TAF) to provide dual HIV/HBV activity 4, 5
• Lamivudine also has anti-HBV activity but tenofovir is preferred 4
• Never discontinue tenofovir without alternative HBV suppressive therapy - risk of hepatitis flare 5

Renal Impairment

• Avoid or dose-adjust TDF if creatinine clearance <60 mL/min 2
• TAF is preferred over TDF for patients with kidney disease 1
• Monitor renal function regularly during treatment 4, 2

Tuberculosis Co-infection

• Efavirenz-based regimens may be preferred due to fewer drug interactions with TB medications 2
• Rifampin significantly reduces levels of many antiretrovirals, requiring dose adjustments 2

Monitoring During Treatment

Virologic Monitoring

• HIV RNA at 2-4 weeks after starting ART 4, 5, 2
• Repeat at 12-24 weeks to confirm undetectable status 4, 5
• Every 3-6 months once suppressed 2

Laboratory Monitoring

• CD4 count at baseline and periodically (though less critical once virologically suppressed) 6
• Renal function tests, especially with tenofovir-containing regimens 4, 2
• Hepatic function tests 4
• Lipid panel if on protease inhibitors 7

Adherence Assessment

• Adherence is the most critical factor for treatment success 3, 8
• Assess at every visit for psychosocial barriers, financial issues, drug interactions, and tolerability 5

Why INSTI-Based Regimens Are Preferred

INSTIs have demonstrated superiority over other drug classes in multiple head-to-head trials:

• Higher rates of virological suppression 1, 2, 3
• Higher genetic barrier to resistance (especially dolutegravir and bictegravir) 4, 2
• Better tolerability profile with fewer discontinuations 1, 7
• Fewer drug-drug interactions compared to boosted protease inhibitors 7
• Rapid viral load decline 1

The evidence supporting INSTI superiority comes from landmark trials including SINGLE (dolutegravir vs efavirenz), FLAMINGO (dolutegravir vs darunavir/r), and ACTG 5257 (raltegravir vs boosted PIs) 1