What is the recommended treatment regimen for managing Human Immunodeficiency Virus (HIV)?

HIV Treatment: Immediate Antiretroviral Therapy Initiation

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

When to Start Treatment

• Initiate ART for all viremic patients with established HIV infection, regardless of CD4 cell count 2
• Start treatment as soon as possible after diagnosis, including same-day initiation if the patient is ready to commit to treatment 1
• For acute HIV infection, immediate ART initiation is strongly recommended to reduce transmission risk, minimize symptoms, and potentially limit viral reservoir size 1
• Do not delay treatment waiting for baseline resistance testing results, though testing should be performed before starting therapy when feasible 3

First-Line Recommended Regimens

Preferred InSTI-based regimens (listed by strength of evidence):

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - single daily pill with high efficacy and favorable side effect profile 1
• Dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine or lamivudine - excellent option for patients with or at risk for kidney or bone disease 1
• Dolutegravir/abacavir/lamivudine - requires mandatory HLA-B*5701 testing first; do NOT use if positive (risk of life-threatening hypersensitivity reaction) 2, 1
• Elvitegravir/cobicistat/TAF/emtricitabine - effective but watch for drug interactions with cobicistat boosting 2
• Raltegravir plus TAF/emtricitabine - alternative InSTI option 2

Critical Pre-Treatment Testing

• HLA-B*5701 testing is mandatory before prescribing any abacavir-containing regimen; approximately 50% of HLA-B*5701-positive individuals will experience potentially life-threatening hypersensitivity reactions 3
• Perform baseline CD4+ cell count, plasma HIV-1 RNA, and HIV resistance testing (though don't delay treatment for results) 4
• Screen for hepatitis B virus (HBV) coinfection before initiating therapy 1

Special Population Considerations

Hepatitis B coinfection:

• Use regimens containing tenofovir (TDF or TAF) plus lamivudine or emtricitabine 2
• Avoid entecavir if HIV RNA is not suppressed (selects for drug-resistant HIV) 2

Hepatitis C coinfection:

• Select ART regimens without significant drug interactions with hepatitis C virus therapies 2

Pregnancy:

• Dolutegravir combined with tenofovir/emtricitabine or lamivudine is recommended 1
• Initiate ART for maternal health and to reduce transmission to infant 2

Kidney or bone disease:

• Avoid tenofovir disoproxil fumarate (TDF) in patients with or at risk for kidney disease (creatinine clearance <60 mL/min) or osteopenia/osteoporosis 2
• Use tenofovir alafenamide (TAF) instead, which has fewer renal and bone toxicities 3
• TAF is not recommended if creatinine clearance is below 30 mL/min 2

Opportunistic infections:

• For most opportunistic infections: initiate ART within 2 weeks of starting treatment 1
• Tuberculosis timing: Start ART within 2 weeks if CD4 <50/μL; within 2-8 weeks if CD4 ≥50/μL 1
• Cryptococcal meningitis timing: Delay ART for 2-4 weeks after starting antifungal therapy to reduce risk of immune reconstitution inflammatory syndrome 1

Why InSTI-Based Regimens Are Preferred

• InSTI-based regimens achieve significantly faster viral suppression compared to protease inhibitor-based regimens (median 1.8 months vs 4.3 months) 5, 6
• Higher rates of virologic suppression overall compared to other drug classes 3
• Favorable side effect profile with fewer toxicities 7
• High barrier to resistance, particularly with dolutegravir 1

Monitoring Requirements

• Monitor HIV RNA viral load every 6 months once stable suppression is achieved 2
• Check estimated glomerular filtration rate, urinalysis, glycosuria, and albuminuria/proteinuria at ART initiation, when changed, and every 6 months 2
• Discontinue tenofovir if renal function worsens, particularly with evidence of proximal tubular dysfunction 2
• Assess adherence at each visit, as this is critical for treatment success 3

Common Pitfalls to Avoid

• Never prescribe abacavir without HLA-B*5701 testing—this can cause life-threatening hypersensitivity reactions 3
• Do not use TDF in patients with kidney disease, osteopenia, or osteoporosis 2
• Do not delay ART initiation—early treatment is associated with better outcomes and faster viral suppression 5, 6
• Do not overlook drug interactions, particularly with cobicistat-boosted regimens 3
• Do not alter regimens for virologic blips (transient low-level viremia) in patients with otherwise suppressed viral load 4

Expected Outcomes

• With effective ART and retention in care, survival rates among HIV-infected adults can approach those of uninfected adults 2, 1
• Patients with continuously undetectable viral load on ART pose virtually no risk of transmitting infection through sexual contact (U=U: undetectable equals untransmittable) 4
• Same-day ART initiation achieves viral suppression in 79% at week 12,82% at week 24, and 88% at week 48 6