Initial HIV Treatment Regimens

First-Line Regimen Recommendations

The American College of Physicians recommends an integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) as the optimal initial regimen for HIV treatment, with bictegravir and dolutegravir being the preferred InSTIs due to their high barrier to resistance and low pill burden 1, 2
Bictegravir-based regimens are recommended as first-line therapy, with bictegravir approved in 2018 as part of a complete regimen for HIV-1 treatment in adults and pediatric patients weighing at least 14 kg 1
Dolutegravir-based regimens are also recommended as first-line therapy, with substantial data and longer-term experience supporting their use 1, 3
Both bictegravir and dolutegravir do not require pharmacologic boosting, have high barriers to resistance, and are associated with low pill burden and toxicity 1
These InSTI-based regimens have shown comparable efficacy with no emergence of resistant virus in initial treatment studies 3

Tenofovir-based backbones (either tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF]) with emtricitabine or lamivudine are recommended 1, 3
TAF results in lower plasma levels of tenofovir and higher intracellular concentration compared to TDF, with similar virologic efficacy 3
Abacavir/lamivudine is an alternative backbone option, particularly when combined with dolutegravir, though HLA-B*5701 testing must be performed before use to avoid hypersensitivity reactions 1, 3

Efavirenz and rilpivirine combined with 2 NRTIs demonstrate high rates of virologic suppression but have more adverse effects than InSTI-based regimens 1, 3
Rilpivirine has fewer central nervous system adverse effects than efavirenz but must be taken with food and is only recommended for patients with baseline HIV RNA <100,000 copies/mL and CD4 count >200/μL 3
Doravirine has shown non-inferiority to efavirenz and ritonavir-boosted darunavir with fewer central nervous system adverse events, though no prospective studies compare it with InSTI-based regimens 3
Boosted protease inhibitors (PIs) like darunavir/ritonavir combined with 2 NRTIs are effective alternatives but have more side effects and drug interactions 4

Long-acting injectable formulations of cabotegravir (InSTI) and rilpivirine (NNRTI) have shown efficacy in maintaining virologic suppression when administered intramuscularly every 4-8 weeks 4
Two-drug regimens are under investigation as alternatives to standard three-drug regimens, potentially offering cost or toxicity advantages 1, 3

HIV RNA level testing is recommended within 6 weeks of starting ART, then every 3 months until viral load is <50 copies/mL for 1 year, then every 6 months 5
Regular monitoring for drug toxicities is essential, particularly renal function for patients on TDF and neuropsychiatric symptoms for patients on efavirenz 5
Genotype resistance testing should be performed before initiating therapy to guide regimen selection 2

Prior to selecting a regimen, consider patient-specific factors including concomitant conditions, pregnancy potential, drug interactions, and cost 2
For patients with hepatitis B co-infection, avoid abacavir-based regimens as abacavir has no activity against hepatitis B virus 3
For patients with renal impairment, TDF should be avoided or dose-adjusted if creatinine clearance is below 60 mL/min 5
Adherence to ART is crucial for treatment success; long-acting injectable options may be considered for patients with adherence challenges 4
When switching regimens due to intolerance or simplification, ensure the new regimen contains at least two or three active drugs based on treatment history and resistance testing 2