The four regimens currently recommended for the initial treatment of most people with HIV infection combine a two-drug NRTI backbone with a third antiretroviral drug from the INSTI class, as follows:

Dolutegravir/abacavir/lamivudine (if HLA-B*5701 negative)

Dolutegravir + emtricitabine/tenofovir alafenamide (tenofovir AF) or tenofovir disoproxil fumarate (tenofovir DF)

Raltegravir + emtricitabine/tenofovir AF or tenofovir DF

Bictegravir/emtracitabine/tenofovir AF

Integrase inhibitor-based therapy has become the preferred option for ART based on the results of randomised clinical trials involving raltegravir or dolutegravir, which showed superiority over other third agents, such as efavirenz or darunavir [15,16]. Elvitegravir has been shown to be non-inferior to either efavirenz or atavanavir boosted with ritonavir in clinical trials [17]. Bictegravir has been shown to be non-inferior to dolutegravir-based ART [18,19]. Notably, there have been no reported cases of dolutegravir or bictegravir resistance recorded in virologically failing subjects in clinical trials involving ART-naïve individuals. In addition to the above three drug combinations, two drug combinations of dolutegravir and lamivudine and dolutegravir and rilpivirine are also approved for use.

Other antiretroviral drugs are largely reserved for the treatment of drug-resistant strains of HIV, including maraviroc, etravirine and enfuvirtide. New regimens that include these types of antiretroviral drugs in treatment-experienced patients with virological failure should include at least two, and preferably three, fully active drugs. In this context, the expected activity of an antiretroviral drug should be based on the patient’s prior treatment history and drug-resistance testing results.