Antiretroviral Therapy in Adults with HIV

Initial Treatment Regimens

The American College of Physicians recommends initiating antiretroviral therapy (ART) immediately upon HIV diagnosis with a recommended integrase strand transfer inhibitor (INSTI)-based regimen, prioritizing single-tablet formulations for optimal adherence and virological suppression 1
Single-tablet regimens are strongly preferred as they improve adherence and simplify treatment 1
Bictegravir/tenofovir alafenamide/emtricitabine is a recommended initial regimen with an evidence rating of AIa 1, 2
Dolutegravir/abacavir/lamivudine is a recommended initial regimen, but should only be used if HLA-B*5701 negative, with an evidence rating of AIa 1
Dolutegravir/tenofovir alafenamide/emtricitabine is a recommended initial regimen with an evidence rating of AIa 1

For patients with suspected multidrug resistance, darunavir/cobicistat/tenofovir alafenamide/emtricitabine is a recommended alternative regimen 1, 3
For patients at high risk of poor adherence, dolutegravir plus tenofovir disoproxil fumarate/lamivudine is a recommended alternative regimen 1
For patients with high risk of drug-drug interactions, raltegravir plus tenofovir alafenamide/emtricitabine is a recommended alternative regimen 1, 4
For patients with HIV/tuberculosis co-infection or pregnancy, efavirenz (400-600 mg) plus tenofovir disoproxil fumarate/emtricitabine is a recommended alternative regimen 1, 3

Virological failure is defined as HIV RNA >200 copies/mL and should be confirmed before switching regimens 2, 6
Never add a single active agent to a failing regimen 2, 6, 7
After NNRTI failure, use dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (nRTIs) with ≥1 active drug determined by genotypic testing 2, 6, 7
After INSTI failure, use a boosted protease inhibitor plus 2 nRTIs with ≥1 active nRTI 2, 6, 7

In patients with sustained viral suppression, switching from a 3-drug to a 2-drug regimen is appropriate to manage toxicity, intolerance, adherence issues, or patient preference, provided both agents are fully active 2, 6, 7
Dolutegravir/rilpivirine is a recommended 2-drug regimen with an evidence rating of AIa 2, 6, 7
Boosted protease inhibitor with lamivudine is a recommended 2-drug regimen with an evidence rating of AIa 2, 6, 7
Dolutegravir/lamivudine is a recommended 2-drug regimen with an evidence rating of AIa 2, 6, 7

Patients with chronic hepatitis B must continue tenofovir (alafenamide or disoproxil fumarate) to maintain HBV suppression when switching HIV regimens 6, 7, 5
Risk of severe hepatitis flare or hepatic decompensation exists if tenofovir is discontinued, particularly in patients with cirrhosis 5

Close and sustained attention to polypharmacy is mandatory in older people with HIV 1, 3, 4
Assess mobility and frailty in all patients ≥50 years using a validated frailty assessment tool 1, 3, 4
Routine cognitive function assessment every 2 years using a validated instrument is recommended for people with HIV older than 60 years 1, 3, 4

Review all co-medications to ensure no dosing adjustments are needed, particularly with tenofovir alafenamide 2, 6, 7
Virological failure with protease inhibitors is rare and usually reflects adherence issues rather than resistance; support adherence or switch to a more tolerable regimen 2, 6, 7