What is the recommended treatment for HIV?

TLD HIV Treatment Recommendation

Start antiretroviral therapy (ART) immediately upon HIV diagnosis, ideally within 7 days or even on the same day if the patient is ready and there is no suspicion of opportunistic infection, using an integrase strand transfer inhibitor (InSTI)-based regimen as first-line treatment. 1

Timing of ART Initiation

• Initiate ART as soon as possible after HIV diagnosis, including at the first clinic visit if the patient is ready to commit to treatment 1
• Same-day initiation (rapid start) is recommended when clinically appropriate and has been shown to achieve viral suppression faster (median 1.8 months) compared to delayed initiation (4.3 months) 2
• Remove structural barriers that delay ART receipt to allow newly diagnosed persons to start treatment at the first clinic visit 1
• For acute HIV infection, immediate ART initiation is strongly recommended 1

First-Line Recommended Regimens

The preferred initial regimens consist of an InSTI plus 2 nucleoside reverse transcriptase inhibitors (NRTIs): 1

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - evidence rating AIa 1
• Dolutegravir (DTG) plus tenofovir alafenamide or tenofovir disoproxil fumarate/emtricitabine or lamivudine - evidence rating AIa 1
• Dolutegravir/abacavir/lamivudine - evidence rating AIa (requires HLA-B*5701 testing first) 1

These regimens are recommended due to high viral suppression rates, excellent tolerability, infrequent toxicity, limited drug-drug interactions, high barrier to resistance, and low pill burden 1

Special Considerations for TLD (Tenofovir/Lamivudine/Dolutegravir)

TLD is a widely used fixed-dose combination, particularly in resource-limited settings, containing:

• Tenofovir disoproxil fumarate (TDF) 300 mg
• Lamivudine (3TC) 300 mg
• Dolutegravir (DTG) 50 mg

Key advantages of TLD:

• Single daily pill regimen enhancing adherence 1
• High barrier to resistance with dolutegravir 1
• Cost-effective, especially in low- and middle-income countries 1

Important caveats for TLD use:

• Avoid tenofovir disoproxil fumarate (TDF) in individuals with or at risk of kidney disease or bone disease (osteopenia/osteoporosis); use tenofovir alafenamide (TAF) instead 1
• Perform HBV screening before initiation, as tenofovir is active against hepatitis B 1
• For pregnant women, dolutegravir is recommended (evidence rating AIb) combined with tenofovir/emtricitabine or lamivudine 1

Baseline Laboratory Testing Before Starting TLD

Required tests before initiating ART: 3

• CD4+ cell count
• HIV RNA viral load
• HIV genotype resistance testing
• HLA-B*5701 testing (if considering abacavir-containing regimens)
• Hepatitis B and C serology
• Basic chemistry panel (including creatinine for renal function assessment)
• Liver function tests
• Pregnancy test in women of childbearing potential

Monitoring After TLD Initiation

• Measure viral load 4-6 weeks after starting ART to assess initial response 3
• Once viral suppression is achieved (<200 copies/mL), monitor every 3 months until suppression is maintained for at least 1 year 3
• After 1 year of sustained viral suppression, monitoring can be reduced to every 6 months 3
• Monitor renal function (creatinine, estimated GFR) at baseline, 2-4 weeks after initiation, and then every 3-6 months due to tenofovir's potential nephrotoxicity 4

Special Situations Requiring Modified Timing

For most opportunistic infections: Initiate ART within 2 weeks of starting treatment for the opportunistic infection 1

For tuberculosis:

• If CD4 count ≥50/μL: Start ART within 2-8 weeks of initiating TB treatment 1
• If CD4 count <50/μL: Start ART within 2 weeks of initiating TB treatment 1
• Important: Dolutegravir requires dose adjustment to 50 mg twice daily when used with rifampin-based TB treatment 1

For cryptococcal meningitis: Initiate ART 2-4 weeks after starting antifungal therapy, with earlier initiation at 2 weeks for those who have clinically improved and have controlled intracranial pressure 1

For TB meningitis: Initiate high-dose corticosteroids and TB treatment immediately, then start ART when TB meningitis is under control (typically 2-4 weeks after starting TB treatment) 1

Common Pitfalls to Avoid

• Do not delay ART initiation - delaying treatment leads to poorer outcomes and increased risk of HIV transmission 3
• Do not use TDF in patients with renal impairment (creatinine clearance <60 mL/min) or bone disease; switch to TAF-based regimens 1
• Do not use bictegravir with rifampin due to significant drug-drug interactions in TB co-infection 1
• Do not skip HBV testing - if HBV co-infection is present, ensure the regimen contains tenofovir (TDF or TAF) plus lamivudine or emtricitabine 1
• Do not assume adherence - provide intensive support, social needs assessment, and frequent follow-up, especially with rapid-start protocols 2
• Do not continue TDF if renal toxicity develops - switch to TAF-based regimen 1

Expected Outcomes with TLD

• Viral suppression (<200 copies/mL) typically achieved within 12-24 weeks of consistent therapy 5
• With rapid-start protocols using integrase inhibitor-based regimens like TLD, viral suppression can occur even faster (median 1.8 months) 2, 6
• Patients with undetectable viral load on ART pose virtually no risk of transmitting HIV through sexual contact (U=U: Undetectable = Untransmittable) 5
• Survival rates among HIV-infected adults retained in care can approach those of uninfected adults 1, 7