What is the recommended initial regimen for HIV treatment-naive patients?

Cabenuva (Cabotegravir + Rilpivirine) is NOT Recommended for Initial HIV Treatment in Treatment-Naïve Patients

Cabenuva should not be used to initiate antiretroviral therapy in treatment-naïve patients—it is only approved for use as a replacement regimen in individuals who are already virologically suppressed on a stable oral antiretroviral regimen. 1, 2, 3

Why Cabenuva Cannot Be Used First-Line

• Cabotegravir is approved only for continuation therapy, not for initial treatment of HIV infection in treatment-naïve adults 3
• The drug is specifically indicated to replace current antiretroviral therapy in individuals who maintain virologic suppression on a stable regimen without history of treatment failure and no known resistance 3
• Patients must first achieve viral suppression with an oral regimen before transitioning to long-acting injectable cabotegravir 3

Recommended Initial Regimens for Treatment-Naïve Patients

The preferred first-line regimen for most treatment-naïve patients is bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) due to its high efficacy, favorable side effect profile, and high barrier to resistance 1

Other Strongly Recommended Initial Regimens (InSTI-Based):

• Dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) - highly effective with strong resistance profile 4, 1
• Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) - requires mandatory HLA-B*5701 testing before use to prevent potentially life-threatening hypersensitivity reactions 4, 1
• Elvitegravir/cobicistat/TAF/emtricitabine - effective but has more drug interactions due to cobicistat boosting 4
• Raltegravir plus TAF/emtricitabine - effective first-generation INSTI option 4

Why InSTI-Based Regimens Are Preferred:

• InSTI-based regimens achieve superior virologic suppression rates compared to protease inhibitor and NNRTI-based regimens 4, 5, 3
• Second-generation INSTIs (dolutegravir, bictegravir) have a high genetic barrier to resistance with minimal resistance mutations observed in clinical trials 4, 3
• These regimens demonstrate excellent tolerability with low discontinuation rates 3
• Limited drug-drug interactions compared to boosted protease inhibitors 3

Alternative Two-Drug Regimen (With Restrictions):

• Dolutegravir/lamivudine (DTG/3TC) can be used ONLY if:
  • HIV RNA level is <500,000 copies/mL 1
  • No lamivudine resistance present 1
  • No hepatitis B co-infection 1, 6
  • Limited data in patients with CD4 counts <200 cells/μL 6

When to Consider Protease Inhibitor-Based Regimens:

• Darunavir (boosted with ritonavir or cobicistat) plus TAF/FTC should be used when InSTI resistance is suspected, particularly after exposure to long-acting cabotegravir as PrEP 1

Critical Pre-Treatment Requirements:

• Baseline resistance testing is mandatory before initiating therapy, though treatment may begin before results are available 4, 5
• HLA-B*5701 testing must be performed before prescribing any abacavir-containing regimen 4, 1
• Assess for hepatitis B and C co-infection, as this affects regimen selection 1, 5

Timing of Treatment Initiation:

• ART should be initiated immediately after HIV diagnosis, including at the first clinic visit if the patient is ready to commit to treatment 2
• For acute HIV infection, immediate ART initiation is strongly recommended 4, 2
• Delaying ART initiation leads to poorer outcomes and increased risk of HIV transmission 2, 5

Common Pitfalls to Avoid:

• Never use Cabenuva as initial therapy—it requires prior viral suppression on oral ART 3
• Not testing for HLA-B*5701 before prescribing abacavir can result in potentially fatal hypersensitivity reactions 4, 1, 5
• Starting DTG/3TC without confirming HIV RNA level, resistance status, and HBV status 1
• Overlooking drug interactions, particularly with cobicistat-boosted regimens or in patients taking rifampin 1
• Using abacavir in patients at high cardiovascular risk remains controversial 4

Monitoring After Initiation:

• Measure viral load 4-6 weeks after starting ART to assess initial response 1, 2
• Once viral suppression is achieved, monitor every 3 months until suppression is maintained for at least 1 year 1, 2
• After 1 year of viral suppression, monitoring can be reduced to every 6 months 1, 2

Special Populations:

• For pregnant patients: DTG plus TAF/FTC is the recommended regimen; BIC/TAF/FTC is an alternative 1
• For patients with renal impairment: avoid TDF-containing regimens 1
• For patients with osteoporosis: prefer TAF over TDF 1
• For hepatitis B co-infection: use regimens containing TAF or TDF plus FTC or 3TC (avoid DTG/3TC) 1