What are the latest treatment recommendations for a patient with Human Immunodeficiency Virus (HIV)?

Latest HIV Treatment Recommendations

All HIV-infected individuals should start antiretroviral therapy (ART) immediately upon diagnosis with an integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) as the preferred first-line regimen. 1, 2

When to Initiate Treatment

• Start ART as soon as possible after HIV diagnosis, ideally at the first clinic visit if the patient is ready to commit to treatment. 1, 2, 3
• Treatment should begin regardless of CD4 cell count or viral load to prevent disease progression, improve clinical outcomes, and limit transmission. 1, 3
• For acute HIV infection, immediate ART initiation is strongly recommended. 2, 4
• Structural barriers delaying ART receipt should be removed to enable same-day treatment initiation. 4

Preferred First-Line Regimens

The following InSTI-based regimens are recommended with the highest evidence ratings:

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - single-tablet regimen with evidence rating AIa 1, 2, 4
• Dolutegravir plus tenofovir alafenamide or tenofovir disoproxil fumarate/emtricitabine or lamivudine - evidence rating AIa 1, 2, 4
• Dolutegravir/abacavir/lamivudine - requires HLA-B*5701 testing first to avoid hypersensitivity reactions, evidence rating AIa 2

Special Consideration: TLD (Tenofovir/Lamivudine/Dolutegravir)

• TLD is a widely used fixed-dose combination containing tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg, and dolutegravir 50 mg, particularly valuable in resource-limited settings. 2
• Key advantages include single daily pill dosing enhancing adherence, high barrier to resistance with dolutegravir, and cost-effectiveness. 2
• Avoid tenofovir disoproxil fumarate (TDF) in patients with or at risk for kidney disease or bone disease; consider tenofovir alafenamide (TAF) instead. 2
• Perform hepatitis B screening before initiation as discontinuation may cause HBV flare. 2

Required Baseline Testing Before Starting ART

Obtain the following tests before initiating therapy:

• CD4+ cell count and HIV RNA level 1
• HIV genotype resistance testing 1
• HLA-B*5701 testing if considering abacavir-containing regimens 4
• Hepatitis B surface antigen and hepatitis C antibody 1
• Basic chemistry panel including serum creatinine for renal function 1
• Liver function tests 4

Monitoring After Treatment Initiation

• Assess viral load 4-6 weeks after starting ART to evaluate initial response and adherence. 1, 4
• HIV RNA suppression typically occurs within 24 weeks, faster with InSTI-based regimens. 1
• Once HIV RNA is below 50 copies/mL, monitor every 3 months until suppressed for at least 1 year. 1, 4
• After 1 year of sustained viral suppression with consistent adherence, monitoring intervals can extend to every 6 months. 1, 4
• CD4 cell counts should be measured every 6 months until above 250/μL for at least 1 year with concomitant viral suppression, then can be discontinued unless virologic failure occurs. 1

Special Timing Considerations with Opportunistic Infections

ART initiation timing must be modified in specific opportunistic infections:

• For most opportunistic infections: Initiate ART within 2 weeks of starting treatment for the infection. 2, 4
• For tuberculosis with CD4 ≥50 cells/μL: Start ART within 2-8 weeks of initiating TB treatment. 2, 4
• For tuberculosis with CD4 <50 cells/μL: Start ART within 2 weeks of initiating TB treatment. 2
• For cryptococcal meningitis: Delay ART for 2-4 weeks after starting antifungal therapy, initiating at 2 weeks for those who have clinically improved with controlled intracranial pressure. 2, 4
• For TB meningitis: Initiate ART when TB meningitis is controlled, typically 2-4 weeks after starting TB treatment. 4

Switching Regimens in Virologically Suppressed Patients

When switching therapy in patients with undetectable viral load:

• Review complete ART history, prior resistance testing results, tolerability, co-medications, and cost before making changes. 1
• Assess viral load 1 month after switching regimens. 1
• Two-drug regimens are appropriate alternatives to reduce toxicity, improve tolerability, or address patient preference, provided both agents are fully active. 1

Recommended 2-drug maintenance regimens include:

• Dolutegravir/rilpivirine (evidence rating AIa) 1
• Dolutegravir/lamivudine (evidence rating AIa) 1
• Boosted protease inhibitor with lamivudine (evidence rating AIa) 1
• Long-acting injectable cabotegravir and rilpivirine every 4 weeks (evidence rating AIa) or every 8 weeks (evidence rating BIb) 1

Critical Switching Caveats

• In HIV/HBV co-infection, continue tenofovir alafenamide or tenofovir disoproxil fumarate to maintain HBV suppression; switching to lamivudine/emtricitabine alone without tenofovir is not recommended. 1
• In patients with NRTI resistance mutations, do not switch from a boosted protease inhibitor to regimens containing drugs with low genetic barriers (NNRTIs or raltegravir). 1
• Monotherapy with boosted protease inhibitors or dolutegravir is not recommended due to higher rates of virologic rebound with resistant virus. 1

Managing Virologic Failure

Virologic failure is defined as HIV RNA >200 copies/mL and should be confirmed with repeat testing. 1

• Obtain resistance testing while the patient is taking the failing regimen or within 4 weeks of stopping ART. 1
• Investigate adherence issues, drug-drug interactions, and review all historical resistance mutations. 1
• Never add a single active agent to a failing regimen. 1

Specific salvage strategies based on initial regimen failure:

• For NNRTI-based regimen failure: Switch to dolutegravir plus 2 NRTIs (with ≥1 active drug by genotype) - evidence rating AIa. 1
• For InSTI-based regimen failure (without resistance): Switch to boosted protease inhibitor plus 2 NRTIs (with ≥1 active NRTI) - evidence rating AIII. 1
• For raltegravir or elvitegravir resistance: Use dolutegravir 50 mg twice daily plus at least 1 fully active agent - evidence rating BIII. 1
• For protease inhibitor failure: Virologic failure with resistance mutations is rare; focus on adherence support or alternative regimens improving tolerability - evidence rating AIII. 1

Multiclass Resistance

• For 3-class resistance: Construct regimens using drugs from new classes including fostemsavir (evidence rating AIb) or ibalizumab (evidence rating BII) with at least 1 additional active drug in an optimized regimen. 1
• Ibalizumab is an anti-CD4 monoclonal antibody active against both CCR5- and CXCR4-tropic HIV; approximately 50% of adults with multidrug-resistant HIV achieved undetectable viral loads at 24 weeks with biweekly intravenous ibalizumab 800 mg plus at least 1 other active drug. 1

Pregnancy Considerations

• Dolutegravir is recommended for pregnant women (evidence rating AIb) combined with tenofovir/emtricitabine or lamivudine. 2

Expected Clinical Outcomes

• With effective modern ART regimens, survival rates among HIV-infected adults retained in care approach those of uninfected adults. 1, 2, 3
• Current regimens can sustain HIV suppression and prevent new HIV infections when used effectively. 1, 3

Common Pitfalls to Avoid

• Delaying ART initiation leads to poorer outcomes and increased HIV transmission risk. 4
• Extending monitoring intervals beyond 6 months when adherence is inconsistent allows more time for resistance to emerge if therapy fails. 1
• Switching to regimens excluding tenofovir in HIV/HBV co-infection without alternative HBV therapy causes HBV reactivation. 1
• Using monotherapy or adding single agents to failing regimens promotes rapid resistance development. 1